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Sample records for cardiac development remodeling

  1. Cardiac remodelling and RAS inhibition.

    Science.gov (United States)

    Ferrario, Carlos M

    2016-06-01

    Risk factors such as hypertension and diabetes are known to augment the activity and tissue expression of angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system (RAS). Overstimulation of the RAS has been implicated in a chain of events that contribute to the pathogenesis of cardiovascular (CV) disease, including the development of cardiac remodelling. This chain of events has been termed the CV continuum. The concept of CV disease existing as a continuum was first proposed in 1991 and it is believed that intervention at any point within the continuum can modify disease progression. Treatment with antihypertensive agents may result in regression of left ventricular hypertrophy, with different drug classes exhibiting different degrees of efficacy. The greatest decrease in left ventricular mass is observed following treatment with angiotensin converting enzyme inhibitors (ACE-Is), which inhibit Ang II formation. Although ACE-Is and angiotensin receptor blockers (ARBs) provide significant benefits in terms of CV events and stroke, mortality remains high. This is partly due to a failure to completely suppress the RAS, and, as our knowledge has increased, an escape phenomenon has been proposed whereby the human sequence of the 12 amino acid substrate angiotensin-(1-12) is converted to Ang II by the mast cell protease, chymase. Angiotensin-(1-12) is abundant in a wide range of organs and has been shown to increase blood pressure in animal models, an effect abolished by the presence of ACE-Is or ARBs. This review explores the CV continuum, in addition to examining the influence of the RAS. We also consider novel pathways within the RAS and how new therapeutic approaches that target this are required to further reduce Ang II formation, and so provide patients with additional benefits from a more complete blockade of the RAS. PMID:27105891

  2. Cardiac Remodeling After Atrial Fibrillation Ablation

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    Li-Wei Lo, MD; Shih-Ann Chen, MD

    2013-06-01

    Full Text Available Radiofrequency catheter ablation procedures are considered a reasonable option for patients with symptomatic, drug refractory atrial fibrillation (AF. Ablation procedures have been reported to effectively restore sinus rhythm and provide long-term relief of symptoms. Both electrical and structural remodeling occurs with AF. A reversal of the electrical remodeling develops within 1 week after restoration to sinus rhythm following the catheter ablation. The recovery rate is faster in the right atrium than the left atrium. Reverse structural remodeling takes longer and is still present 2 to 4 months after restoration of sinus rhythm. The left atrial transport function also improves after successful catheter ablation of AF. Left atrial strain surveys from echocardiography are able to identify patients who respond to catheter ablation with significant reverse remodeling after ablation. Pre-procedural delayed enhancement magnetic resonance imaging is also able to determine the degree of atrial fibrosis and is another tool to predict the reverse remodeling after ablation. The remodeling process is complex if recurrence develops after ablation. Recent evidence shows that a combined reverse electrical and structural remodeling occurs after ablation of chronic AF when recurrence is paroxysmal AF. Progressive electrical remodeling without any structural remodeling develops in those with recurrence involving chronic AF. Whether progressive atrial remodeling is the cause or consequence during the recurrence of AF remains obscure and requires further study.

  3. Hypothyroidism and its rapid correction alter cardiac remodeling.

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    Georges Hajje

    Full Text Available The cardiovascular effects of mild and overt thyroid disease include a vast array of pathological changes. As well, thyroid replacement therapy has been suggested for preserving cardiac function. However, the influence of thyroid hormones on cardiac remodeling has not been thoroughly investigated at the molecular and cellular levels. The purpose of this paper is to study the effect of hypothyroidism and thyroid replacement therapy on cardiac alterations. Thirty Wistar rats were divided into 2 groups: a control (n = 10 group and a group treated with 6-propyl-2-thiouracil (PTU (n = 20 to induce hypothyroidism. Ten of the 20 rats in the PTU group were then treated with L-thyroxine to quickly re-establish euthyroidism. The serum levels of inflammatory markers, such as C-reactive protein (CRP, tumor necrosis factor alpha (TNF-α, interleukin 6 (IL6 and pro-fibrotic transforming growth factor beta 1 (TGF-β1, were significantly increased in hypothyroid rats; elevations in cardiac stress markers, brain natriuretic peptide (BNP and cardiac troponin T (cTnT were also noted. The expressions of cardiac remodeling genes were induced in hypothyroid rats in parallel with the development of fibrosis, and a decline in cardiac function with chamber dilation was measured by echocardiography. Rapidly reversing the hypothyroidism and restoring the euthyroid state improved cardiac function with a decrease in the levels of cardiac remodeling markers. However, this change further increased the levels of inflammatory and fibrotic markers in the plasma and heart and led to myocardial cellular infiltration. In conclusion, we showed that hypothyroidism is related to cardiac function decline, fibrosis and inflammation; most importantly, the rapid correction of hypothyroidism led to cardiac injuries. Our results might offer new insights for the management of hypothyroidism-induced heart disease.

  4. Intradialytic Hypotension and Cardiac Remodeling: A Vicious Cycle

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    Chia-Ter Chao

    2015-01-01

    Full Text Available Hemodynamic instability during hemodialysis is a common but often underestimated issue in the nephrologist practice. Intradialytic hypotension, namely, a decrease of systolic or mean blood pressure to a certain level, prohibits the safe and smooth achievement of ultrafiltration and solute removal goal in chronic dialysis patients. Studies have elucidated the potential mechanisms involved in the development of Intradialytic hypotension, including excessive ultrafiltration and loss of compensatory mechanisms for blood pressure maintenance. Cardiac remodeling could also be one important piece of the puzzle. In this review, we intend to discuss the role of cardiac remodeling, including left ventricular hypertrophy, in the development of Intradialytic hypotension. In addition, we will also provide evidence that a bidirectional relationship might exist between Intradialytic hypotension and left ventricular hypertrophy in chronic dialysis patients. A more complete understanding of the complex interactions in between could assist the readers in formulating potential solutions for the reduction of both phenomena.

  5. Cardiac electrical remodeling in health and disease

    OpenAIRE

    Cutler, Michael J.; Jeyaraj, Darwin; Rosenbaum, David S.

    2011-01-01

    Electrical remodeling of the heart occurs in response to both functional (i.e. altered electrical activation) and structural (i.e. heart failure, myocardial infarction, etc.) stressors. These electrophysiological changes produce a substrate that is vulnerable to malignant ventricular arrhythmias. Understanding the cellular and molecular mechanisms of electrical remodeling is important in elucidating potential therapeutic targets designed to alter maladaptive electrical remodeling. For example...

  6. Ouabain induces cardiac remodeling in rats independent of blood pressure

    Institute of Scientific and Technical Information of China (English)

    Xing JIANG; Yan-ping REN; Zhuo-ren L(U)

    2007-01-01

    Aim: To investigate the ouabain's effects on cardiac remodeling in rats. Methods:Male Sprague-Dawley rats were treated with ouabain. Systolic blood pressure(SBP) was recorded weekly. After 4 and 6 weeks, echocardiography were performed,hemodynamic parameters were measured by invasive cardiac catheterization,changes in cardiac ultrastructure were analyzed using transmission electron microscopy, the collagen fraction of the left ventricle was assessed with Picrosirius red stain, and RT-PCR was applied to evaluate the mRNA level of myosin heavy chain-α and-β in the left ventricle. Results: Having been treated with ouabain for 4 weeks, there was no significant difference in the mean SBP of the two groups.However, left ventricular hypertrophy, myocardial ultrastructure deterioration,and extracellular matrix remodeling were induced by ouabain treatment; meanwhile,cardiac systolic and diastolic performance were both worsened. Moreover, the cardiac MHC-β mRNA was upregulated by ouabain treatment, whereas MHC-αmRNA was downregulated. After 4 weeks, the mean SBP in the ouabain group began to increase and was significantly higher than that in control group after 6 weeks (P<0.01); the rats' cardiac structure and function were worsened.Conclusion: These results suggested that ouabain induces alterations in cardiac structure and function, and the effects happened before the increase of blood pressure. The results indicated that ouabain induced cardiac remodeling in rats independent of blood pressure.

  7. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

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    Marcos Minicucci

    2016-01-01

    Full Text Available Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C, Pentoxifylline (PX, Tobacco Smoke (TS, and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt, and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA and citrate synthase (CS. PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

  8. Mitochondrial Protein Dynamics in Cardiac Remodeling

    OpenAIRE

    Lau, Edward

    2014-01-01

    The cardiac mitochondrial proteome contains ~1,500 distinct proteins that carry out necessary metabolic and energetic processes in the heart. To sustain cardiac function, the mitochondrial proteome must be maintained in constant renewal, or turnover, especially under stress conditions. Disruptions of protein turnover can lead to protein damage and proteotoxicity, a hallmark of many heart disease etiologies. Current quantitative proteomics experiments largely focus on the measurement of the st...

  9. Pay attention to cardiac remodeling in cancer cachexia.

    Science.gov (United States)

    Zheng, Yawen; Chen, Han; Li, Xiaoqing; Sun, Yuping

    2016-07-01

    Cancer cachexia is a complex and multifaceted disease state characterized by fatigue, weakness, and loss of skeletal muscle and adipose tissue. Recently, the profound negative effects of cancer cachexia on cardiac tissue draw much attention, which is likely to contribute to mortality in tumor-bearing animals. The mechanism of cardiac remodeling is not so clear and involved with a series of molecular alterations. In cancer cachexia model, progressive loss of left ventricular mass and decrease in myocardial function is observed and cardiac autonomic functions are altered. Levels of several emerging cardiovascular neurohormones are found elevating in patients with cancer, but it is still controversial whether the changes could reflect the heart injury accurately. The remedy for cardiac remodeling has been explored. It is showed that exercise can modulate signaling pathways activated by wasting cytokines and impact on the resulting outcomes on heart adaptation. Some drugs, such as bisoprolol, spironolactone, perindopril, tandospirone, and simvastatin, can mitigate adverse effects of the tumor on the heart and prolong survival. PMID:27108265

  10. Cardiac remodeling and myocardial dysfunction in obese spontaneously hypertensive rats

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    Linz Dominik

    2012-09-01

    Full Text Available Abstract Background The additive effects of obesity and metabolic syndrome on left ventricular (LV maladaptive remodeling and function in hypertension are not characterized. Methods We compared an obese spontaneously hypertensive rat model (SHR-ob with lean spontaneously hypertensive rats (SHR-lean and normotensive controls (Ctr. LV-function was investigated by cardiac magnetic resonance imaging and invasive LV-pressure measurements. LV-interstitial fibrosis was quantified and protein levels of phospholamban (PLB, Serca2a and glucose transporters (GLUT1 and GLUT4 were determined by immunohistochemistry. Results Systolic blood pressure was similar in SHR-lean and SHR-ob (252 ± 7 vs. 242 ± 7 mmHg, p = 0.398 but was higher when compared to Ctr (155 ± 2 mmHg, p  Conclusion In addition to hypertension alone, metabolic syndrome and obesity adds to the myocardial phenotype by aggravating diastolic dysfunction and a progression towards systolic dysfunction. SHR-ob may be a useful model to develop new interventional and pharmacological treatment strategies for hypertensive heart disease and metabolic disorders.

  11. Cardiac remodeling and physical training post myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Michael; A; Garza; Emily; A; Wason; John; Q; Zhang

    2015-01-01

    After myocardial infarction(MI), the heart undergoes extensive myocardial remodeling through the accumulation of fibrous tissue in both the infarcted and noninfarcted myocardium, which distorts tissue structure, increases tissue stiffness, and accounts for ventricular dysfunction. There is growing clinical consensus that exercise training may beneficially alter the course of post-MI myocardial remodeling and improve cardiac function. This review summarizes the present state of knowledge regarding the effect of post-MI exercise training on infarcted hearts. Due to the degree of difficulty to study a viable human heart at both protein and molecular levels, most of the detailed studies have been performed by using animal models. Although there are some negative reports indicating that post-MI exercise may further cause deterioration of the wounded hearts, a growing body of research from both human and animal experiments demonstrates that post-MI exercise may beneficially alter the course of wound healing and improve cardiac function. Furthermore, the improved function is likely due to exercise training-induced mitigation of reninangiotensin-aldosterone system, improved balance between matrix metalloproteinase-1 and tissue inhibitor of matrix metalloproteinase-1, favorable myosin heavy chain isoform switch, diminished oxidative stress, enhanced antioxidant capacity, improved mitochondrial calcium handling, and boosted myocardial angiogenesis. Additionally, meta-analyses revealed that exercise-based cardiac rehabilitation has proven to be effective, and remains one of the least expensive therapies for both the prevention and treatment of cardiovascular disease, and prevents re-infarction.

  12. Chromatin remodeling, development and disease

    International Nuclear Information System (INIS)

    Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

  13. The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure

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    Shanshan Zhou

    2014-01-01

    Full Text Available Heart failure (HF is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2- related factor 2 (Nrf2 is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.

  14. Aggravated Cardiac Remodeling post Aortocaval Fistula in Unilateral Nephrectomized Rats.

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    Jie Wu

    Full Text Available Aortocaval fistula (AV in rat is a unique model of volume-overload congestive heart failure and cardiac hypertrophy. Living donor kidney transplantation is regarded as beneficial to allograft recipients and not particularly detrimental to the donors. Impact of AV on animals with mild renal dysfunction is not fully understood. In this study, we explored the effects of AV in unilateral nephrectomized (UNX rats.Adult male Sprague-Dawley (SD rats were divided into Sham (n = 10, UNX (right kidney remove, n = 10, AV (AV established between the levels of renal arteries and iliac bifurcation, n = 18 and UNX+AV (AV at one week after UNX, n = 22, respectively. Renal outcome was measured by glomerular filtration rate, effective renal plasma flow, fractional excretion of sodium, albuminuria, plasma creatinine, and cystatin C. Focal glomerulosclerosis (FGS incidence was evaluated by renal histology. Cardiac function was measured by echocardiography and hemodynamic measurements.UNX alone induced compensatory left kidney enlargement, increased plasma creatinine and cystatin C levels, and slightly reduced glomerular filtration rate and increased FGS. AV induced significant cardiac enlargement and hypertrophy and reduced cardiac function and increased FGS, these changes were aggravated in UNX+AV rats.Although UNX only induces minor renal dysfunction, additional chronic volume overload placement during the adaptation phase of the remaining kidney is associated with aggravated cardiac dysfunction and remodeling in UNX rats, suggesting special medical care is required for UNX or congenital monokidney subjects in case of chronic volume overload as in the case of pregnancy and hyperthyroidism to prevent further adverse cardiorenal events in these individuals.

  15. Aging and the cardiac collagen matrix: Novel mediators of fibrotic remodelling.

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    Horn, Margaux A; Trafford, Andrew W

    2016-04-01

    Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways. PMID:26578393

  16. miR-222 is Necessary for Exercise-induced Cardiac Growth and Protects Against Pathological Cardiac Remodeling

    OpenAIRE

    Liu, Xiaojun; Xiao, Junjie; Zhu, Han; Wei, Xin; Platt, Colin; Damilano, Federico; Xiao, Chunyang; Bezzerides, Vassilios; Boström, Pontus; Che, Lin; Zhang, Chunxiang; Spiegelman, Bruce M.; Rosenzweig, Anthony

    2015-01-01

    Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart’s capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregula...

  17. Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression

    Institute of Scientific and Technical Information of China (English)

    Bing-yan GUO; Yong-jun LI; Rui HAN; Shao-1ing YANG; Ying-hui SHI; De-rong HAN; Hong ZHOU; Mei WANG

    2011-01-01

    Aim:To investigate whether telmisartan(Telm)pretreatment attenuates isoproterenol(Iso)-induced postinfarction remodeling(PIR)in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin.Methods:PIR was induced in male Wistar rats with two consecutive injections of Iso(80 mg/kg,sc)at an interval of 24 h.Primary Culture of ventricular myocytes from neonatal rats was prepared.Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase(LDH)activity.Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis.Results:In the rats with PIR.Telm(10 mg·kg-1·d-1,po for 65 d)suppressed lso-induced increases in gravimetric parameters.cardiomyocyte diameter and collagen volume fraction,but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis.The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin.In cultured cardiomyocytes,Telm (5-20 μmol/L)inhibited the celI death and LDH release induced by lSO(10 μmol/L).and reversed Iso-induced reduction in adiponectinprotein expression.In cardiomyocytes exposed to Iso(20 μmol/L).GW9662(30 μmol/L),a selective antagonist of PPAR-v,blocked the effects of Telm Dretreatment on adiponectin protein expression,as well as the protective effects of Telm on Iso-induced celI injUry.Conclusion:Telm attenuates Iso-induced cardiac remodeling and cell injury,which is associated with induction of cardiac adiponectin expression.

  18. Fibroblast growth factor-2 regulates human cardiac myofibroblast-mediated extracellular matrix remodeling

    OpenAIRE

    Svystonyuk, Daniyil A; Ngu, Janet MC; Mewhort, Holly EM; Lipon, Brodie D; Teng, Guoqi; Guzzardi, David G; Malik, Getanshu; Belke, Darrell D.; Fedak, Paul WM

    2015-01-01

    Background Tissue fibrosis and chamber remodeling is a hallmark of the failing heart and the final common pathway for heart failure of diverse etiologies. Sustained elevation of pro-fibrotic cytokine transforming growth factor-beta1 (TGFβ1) induces cardiac myofibroblast-mediated fibrosis and progressive structural tissue remodeling. Objectives We examined the effects of low molecular weight fibroblast growth factor (LMW-FGF-2) on human cardiac myofibroblast-mediated extracellular matrix (ECM)...

  19. Mechanisms of epoxyeicosatrienoic acids to improve cardiac remodeling in chronic renal failure disease.

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    Zhang, Kun; Wang, Ju; Zhang, Huanji; Chen, Jie; Zuo, Zhiyi; Wang, Jingfeng; Huang, Hui

    2013-02-15

    Both clinical and basic science studies have demonstrated that cardiac remodeling in patients with chronic renal failure (CRF) is very common. It is a key feature during the course of heart failure and an important risk factor for subsequent cardiac mortality. Traditional drugs or therapies rarely have effects on cardiac regression of CRF and cardiovascular events are still the first cause of death. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acids metabolized by cytochrome P450 epoxygenases. It has been found that EETs have important biological effects including anti-hypertension and anti-inflammation. Recent data suggest that EETs are involved in regulating cardiomyocyte injury, renal dysfunction, chronic kidney disease (CKD)-related risk factors and signaling pathways, all of which play key roles in cardiac remodeling induced by CRF. This review analyzes the literature to identify the possible mechanisms for EETs to improve cardiac remodeling induced by CRF and indicates the therapeutic potential of EETs in it. PMID:23313758

  20. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

    OpenAIRE

    Jessica Jen-Chu Wang; Christoph Rau; Rozeta Avetisyan; Shuxun Ren; Romay, Milagros C.; Gabriel Stolin; Ke Wei Gong; Yibin Wang; Lusis, Aldons J.

    2016-01-01

    We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with ...

  1. Connexin43 Cardiac Gap Junction Remodeling: Lessons from Genetically Engineered Murine Models

    OpenAIRE

    Remo, Benjamin F.; Giovannone, Steven; Fishman, Glenn I.

    2012-01-01

    Sudden cardiac death is responsible for several hundred thousand deaths each year in the United States. Multiple lines of evidence suggest that perturbation of gap junction expression and function in the heart, or what has come to be known as cardiac gap junction remodeling, plays a key mechanistic role in the pathophysiology of clinically significant cardiac arrhythmias. Here we review recent studies from our laboratory using genetically engineered murine models to explore mechanisms implica...

  2. Deficiency of Smad7 enhances cardiac remodeling induced by angiotensin II infusion in a mouse model of hypertension.

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    Li Hua Wei

    Full Text Available Smad7 has been shown to negatively regulate fibrosis and inflammation, but its role in angiotensin II (Ang II-induced hypertensive cardiac remodeling remains unknown. Therefore, the present study investigated the role of Smad7 in hypertensive cardiopathy induced by angiotensin II infusion. Hypertensive cardiac disease was induced in Smad7 gene knockout (KO and wild-type (WT mice by subcutaneous infusion of Ang II (1.46 mg/kg/day for 28 days. Although equal levels of high blood pressure were developed in both Smad7 KO and WT mice, Smad7 KO mice developed more severe cardiac injury as demonstrated by impairing cardiac function including a significant increase in left ventricular (LV mass (P<0.01,reduction of LV ejection fraction(P<0.001 and fractional shortening(P<0.001. Real-time PCR, Western blot and immunohistochemistry detected that deletion of Smad7 significantly enhanced Ang II-induced cardiac fibrosis and inflammation, including upregulation of collagen I, α-SMA, interleukin-1β, TNF-α, and infiltration of CD3(+ T cells and F4/80(+ macrophages. Further studies revealed that enhanced activation of the Sp1-TGFβ/Smad3-NF-κB pathways and downregulation of miR-29 were mechanisms though which deletion of Smad7 promoted Ang II-mediated cardiac remodeling. In conclusions, Smad7 plays a protective role in AngII-mediated cardiac remodeling via mechanisms involving the Sp1-TGF-β/Smad3-NF.κB-miR-29 regulatory network.

  3. Role of matricellular proteins in cardiac tissue remodeling after myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yutaka; Matsui; Junko; Morimoto; Toshimitsu; Uede

    2010-01-01

    After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.

  4. Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice

    DEFF Research Database (Denmark)

    Patrick, David M; Montgomery, Rusty L; Qi, Xiaoxia;

    2010-01-01

    cardiac hypertrophy and fibrosis in rodents in response to pressure overload. In contrast, we have shown here that miR-21-null mice are normal and, in response to a variety of cardiac stresses, display cardiac hypertrophy, fibrosis, upregulation of stress-responsive cardiac genes, and loss of cardiac......MicroRNAs inhibit mRNA translation or promote mRNA degradation by binding complementary sequences in 3' untranslated regions of target mRNAs. MicroRNA-21 (miR-21) is upregulated in response to cardiac stress, and its inhibition by a cholesterol-modified antagomir has been reported to prevent...... contractility comparable to wild. type littermates. Similarly, inhibition of miR-21 through intravenous delivery of a locked nucleic acid-modified (LNA-modified) antimiR oligonucleotide also failed to block the remodeling response of the heart to stress. We therefore conclude that miR-21 is not essential for...

  5. Cardiac remodelling and function with primary mitral valve insufficiency studied by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Aplin, Mark; Kyhl, Kasper; Bjerre, Jenny;

    2016-01-01

    AIMS: Evaluation of patients with primary mitral valve insufficiency (MI) is best supported by quantitative measures. Cardiovascular magnetic resonance imaging (CMR) offers flow and cardiac chamber volume quantification. We studied cardiac remodelling with CMR to determine MI regurgitation volumes...... (P < 0.05). In surgical patients, the MIVol correlated to the decrease in LV dimension after valve surgery (P < 0.02). CONCLUSION: CMR provides a reproducible quantitative technique for evaluation of MI, as MIVol and cardiac chamber volumes can be held against diagnostic cut-off values. The Aoflow...

  6. A transgenic platform for testing drugs intended for reversal of cardiac remodeling identifies a novel 11βHSD1 inhibitor rescuing hypertrophy independently of re-vascularization.

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    Oren Gordon

    Full Text Available RATIONALE: Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. OBJECTIVES: To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. METHODS AND RESULTS: A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised cardiac function lead to progressive remodeling and eventually heart failure. Ability of candidate drugs administered at sequential remodeling stages to reverse hypertrophy, enlarged LV size and improve cardiac function was monitored. Arguing for clinical relevance of the experimental system, clinically-used drugs operating on the Renin-Angiotensin-Aldosterone-System (RAAS, namely, the ACE inhibitor Enalapril and the direct renin inhibitor Aliskerin fully reversed remodeling. Remodeling reversal by these drugs was not accompanied by neovascularization and reached a point-of-no-return. Similarly, the PPARγ agonist Pioglitazone was proven capable of reversing all aspects of cardiac remodeling without affecting the vasculature. Extending the arsenal of remodeling-reversing drugs to pathways other than RAAS, a specific inhibitor of 11β-hydroxy-steroid dehydrogenase type 1 (11β HSD1, a key enzyme required for generating active glucocorticoids, fully rescued myocardial hypertrophy. This was associated with mitigating the hypertrophy-associated gene signature, including reversing the myosin heavy chain isoform switch but in a pattern distinguishable from that associated with neovascularization-induced reversal. CONCLUSIONS: A system was developed suitable for identifying novel remodeling-reversing drugs operating in different pathways and for gaining insights into their mechanisms of action, exemplified here by uncoupling their vascular affects.

  7. Postnatal ablation of Foxm1 from cardiomyocytes causes late onset cardiac hypertrophy and fibrosis without exacerbating pressure overload-induced cardiac remodeling.

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    Craig Bolte

    Full Text Available Heart disease remains a leading cause of morbidity and mortality in the industrialized world. Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the most common cause of sudden cardiac death. Foxm1 transcription factor (also known as HFH-11B, Trident, Win or MPP2 plays an important role in the pathogenesis of various cancers and is a critical mediator of post-injury repair in multiple organs. Foxm1 has been previously shown to be essential for heart development and proliferation of embryonic cardiomyocytes. However, the role of Foxm1 in postnatal heart development and in cardiac injury has not been evaluated. To delete Foxm1 in postnatal cardiomyocytes, αMHC-Cre/Foxm1(fl/fl mice were generated. Surprisingly, αMHC-Cre/Foxm1(fl/fl mice exhibited normal cardiomyocyte proliferation at postnatal day seven and had no defects in cardiac structure or function but developed cardiac hypertrophy and fibrosis late in life. The development of cardiomyocyte hypertrophy and cardiac fibrosis in aged Foxm1-deficient mice was associated with reduced expression of Hey2, an important regulator of cardiac homeostasis, and increased expression of genes critical for cardiac remodeling, including MMP9, αSMA, fibronectin and vimentin. We also found that following aortic constriction Foxm1 mRNA and protein were induced in cardiomyocytes. However, Foxm1 deletion did not exacerbate cardiac hypertrophy or fibrosis following chronic pressure overload. Our results demonstrate that Foxm1 regulates genes critical for age-induced cardiomyocyte hypertrophy and cardiac fibrosis.

  8. Effects of Hypertension and Exercise on Cardiac Proteome Remodelling

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    Bernardo A. Petriz

    2014-01-01

    Full Text Available Left ventricle hypertrophy is a common outcome of pressure overload stimulus closely associated with hypertension. This process is triggered by adverse molecular signalling, gene expression, and proteome alteration. Proteomic research has revealed that several molecular targets are associated with pathologic cardiac hypertrophy, including angiotensin II, endothelin-1 and isoproterenol. Several metabolic, contractile, and stress-related proteins are shown to be altered in cardiac hypertrophy derived by hypertension. On the other hand, exercise is a nonpharmacologic agent used for hypertension treatment, where cardiac hypertrophy induced by exercise training is characterized by improvement in cardiac function and resistance against ischemic insult. Despite the scarcity of proteomic research performed with exercise, healthy and pathologic heart proteomes are shown to be modulated in a completely different way. Hence, the altered proteome induced by exercise is mostly associated with cardioprotective aspects such as contractile and metabolic improvement and physiologic cardiac hypertrophy. The present review, therefore, describes relevant studies involving the molecular characteristics and alterations from hypertensive-induced and exercise-induced hypertrophy, as well as the main proteomic research performed in this field. Furthermore, proteomic research into the effect of hypertension on other target-demerged organs is examined.

  9. Adenoviral short hairpin RNA targeting phosphodiesterase 5 attenuates cardiac remodeling and cardiac dysfunction following myocardial infarction in mice

    Institute of Scientific and Technical Information of China (English)

    张健

    2014-01-01

    Objective To observe the impact of PDE5shRNA on cardiac remodeling and heart function following myocardial infarction in mice.Methods Myocardial infarction(MI)was induced in mice by left coronary artery ligation.Mice were randomly assigned to sham operation group(n=6),PDE5shRNA group(n=12),common adenovirus group(n=15)and DMEM group(n=8).Four weeks post-MI,the survival rate was evaluated.

  10. Sex-specific cardiac cardiolipin remodelling after doxorubicin treatment

    OpenAIRE

    Moulin, Maryline; Solgadi, Audrey; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée; Chaminade, Pierre

    2015-01-01

    Background Imbalance in lipid metabolism and membrane lipid homeostasis has been observed in numerous diseases including heart failure and cardiotoxicity. Growing evidence links phospholipid alterations especially cardiolipins (CLs) to defects in mitochondrial function and energy metabolism in heart failure. We have shown recently that doxorubicin cardiotoxicity is more severe in male than female Wistar rats. We aimed to study whether this sex specificity is linked to differences in cardiac p...

  11. Early remodeling of rat cardiac muscle induced by swimming training

    Directory of Open Access Journals (Sweden)

    Verzola R.M.M.

    2006-01-01

    Full Text Available The aim of the present investigation was to study the effect of acute swimming training with an anaerobic component on matrix metallopeptidase (MMP activity and myosin heavy chain gene expression in the rat myocardium. Animals (male Wistar rats, weighing approximately 180 g were trained for 6 h/day in 3 sessions of 2 h each for 1 to 5 consecutive days (N = 5 rats per group. Rats swam in basins 47 cm in diameter and 60 cm deep filled with water at 33 to 35ºC. After the training period a significant increase (P < 0.05 was observed in the heart weight normalized to body weight by about 22 and 35% in the groups that trained for 96 and 120 h, respectively. Blood lactate levels were significantly increased (P < 0.05 in all groups after all training sessions, confirming an anaerobic component. However, lactate levels decreased (P < 0.05 with days of training, suggesting that the animals became adapted to this protocol. Myosin heavy chain-ß gene expression, analyzed by real time PCR and normalized with GAPDH gene expression, showed a significant two-fold increase (P < 0.01 after 5 days of training. Zymography analysis of myocardium extracts indicated a single ~60-kDa activity band that was significantly increased (P < 0.05 after 72, 96, and 120 h, indicating an increased expression of MMP-2 and suggesting precocious remodeling. Furthermore, the presence of MMP-2 was confirmed by Western blot analysis, but not the presence of MMP-1 and MMP-3. Taken together, our results indicate that in these training conditions, the rat heart undergoes early biochemical and functional changes required for the adaptation to the new physiological condition by tissue remodeling.

  12. Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.

    Directory of Open Access Journals (Sweden)

    Jessica Jen-Chu Wang

    2016-07-01

    Full Text Available We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls.

  13. TRPV1 gene deletion exacerbates inflammation and atypical cardiac remodeling after myocardial infarction

    OpenAIRE

    Huang, Wei; Rubinstein, Jack; Prieto, Alejandro R.; Thang, Loc Vinh; Wang, Donna H.

    2008-01-01

    The transient receptor potential vanilloid (TRPV1) channels expressed in sensory afferent fibers innervating the heart may be activated by proton or endovanilloids released during myocardial ischemia (MI), leading to angina. Although our previous in vitro data indicate that TRPV1 activation may preserve cardiac function after ischemia-reperfusion (I/R) injury, the underlying mechanisms are largely unknown. To test the hypothesis that TRPV1 modulates inflammatory and early remodeling processes...

  14. Endocrine Alterations Are the Main Determinants of Cardiac Remodelling in Restrictive Anorexia Nervosa

    OpenAIRE

    Guido Carlomagno; Valentina Mercurio; Antonio Ruvolo; Ignazio Senatore; Irina Halinskaya; Valeria Fazio; Flora Affuso; Serafino Fazio

    2011-01-01

    Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for...

  15. Gender Differences in Adiponectin Modulation of Cardiac Remodeling in Mice Deficient in Endothelial Nitric Oxide Synthase

    OpenAIRE

    Durand, Jorge L.; Nawrocki, Andrea R.; Scherer, Philipp E.; Jelicks, Linda A.

    2012-01-01

    Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels...

  16. Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-β1.

    Science.gov (United States)

    Mewhort, Holly E M; Lipon, Brodie D; Svystonyuk, Daniyil A; Teng, Guoqi; Guzzardi, David G; Silva, Claudia; Yong, V Wee; Fedak, Paul W M

    2016-03-15

    Following myocardial infarction (MI), cardiac myofibroblasts remodel the extracellular matrix (ECM), preventing mechanical complications. However, prolonged myofibroblast activity leads to dysregulation of the ECM, maladaptive remodeling, fibrosis, and heart failure (HF). Chronic inflammation is believed to drive persistent myofibroblast activity; however, the mechanisms are unclear. We assessed the influence of peripheral blood monocytes on human cardiac myofibroblast activity in a three-dimensional (3D) ECM microenvironment. Human cardiac myofibroblasts isolated from surgical biopsies of the right atrium and left ventricle were seeded into 3D collagen matrices. Peripheral blood monocytes were isolated from healthy human donors and cocultured with myofibroblasts. Monocytes increased myofibroblast activity measured by collagen gel contraction (baseline: 57.6 ± 5.9% vs. coculture: 65.2 ± 7.1% contraction; P < 0.01) and increased local ECM remodeling quantified by confocal microscopy. Under coculture conditions that allow indirect cellular interaction via paracrine factors but prevent direct cell-cell contact, monocytes had minimal effects on myofibroblast activity (17.9 ± 11.1% vs. 6.4 ± 7.0% increase, respectively; P < 0.01). When cells were cultured under direct contact conditions, multiplex analysis of the coculture media revealed an increase in the paracrine factors TGF-β1 and matrix metalloproteinase 9 compared with baseline (122.9 ± 10.1 pg/ml and 3,496.0 ± 190.4 pg/ml, respectively, vs. 21.5 ± 16.3 pg/ml and 183.3 ± 43.9 pg/ml; P < 0.001). TGF-β blockade abolished the monocyte-induced increase in cardiac myofibroblast activity. These data suggest that direct cell-cell interaction between monocytes and cardiac myofibroblasts stimulates TGF-β-mediated myofibroblast activity and increases remodeling of local matrix. Peripheral blood monocyte interaction with human cardiac myofibroblasts stimulates myofibroblast activity through release of TGF-β1

  17. Temporal and Molecular Analyses of Cardiac Extracellular Matrix Remodeling following Pressure Overload in Adiponectin Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Keith Dadson

    Full Text Available Adiponectin, circulating levels of which are reduced in obesity and diabetes, mediates cardiac extracellular matrix (ECM remodeling in response to pressure overload (PO. Here, we performed a detailed temporal analysis of progressive cardiac ECM remodelling in adiponectin knockout (AdKO and wild-type (WT mice at 3 days and 1, 2, 3 and 4 weeks following the induction of mild PO via minimally invasive transverse aortic banding. We first observed that myocardial adiponectin gene expression was reduced after 4 weeks of PO, whereas increased adiponectin levels were detected in cardiac homogenates at this time despite decreased circulating levels of adiponectin. Scanning electron microscopy and Masson's trichrome staining showed collagen accumulation increased in response to 2 and 4 weeks of PO in WT mice, while fibrosis in AdKO mice was notably absent after 2 weeks but highly apparent after 4 weeks of PO. Time and intensity of fibroblast appearance after PO was not significantly different between AdKO and WT animals. Gene array analysis indicated that MMP2, TIMP2, collagen 1α1 and collagen 1α3 were induced after 2 weeks of PO in WT but not AdKO mice. After 4 weeks MMP8 was induced in both genotypes, MMP9 only in WT mice and MMP1α only in AdKO mice. Direct stimulation of primary cardiac fibroblasts with adiponectin induced a transient increase in total collagen detected by picrosirius red staining and collagen III levels synthesis, as well as enhanced MMP2 activity detected via gelatin zymography. Adiponectin also enhanced fibroblast migration and attenuated angiotensin-II induced differentiation to a myofibroblast phenotype. In conclusion, these data indicate that increased myocardial bioavailability of adiponectin mediates ECM remodeling following PO and that adiponectin deficiency delays these effects.

  18. Post-mortem cardiac diffusion tensor imaging: detection of myocardial infarction and remodeling of myofiber architecture

    Energy Technology Data Exchange (ETDEWEB)

    Winklhofer, Sebastian; Berger, Nicole; Stolzmann, Paul [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Stoeck, Christian T.; Kozerke, Sebastian [Institute for Biomedical Engineering University and ETH Zurich, Zurich (Switzerland); Thali, Michael [University of Zurich, Department of Forensic Medicine and Radiology, Institute of Forensic Medicine, Zurich (Switzerland); Manka, Robert [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Institute for Biomedical Engineering University and ETH Zurich, Zurich (Switzerland); University Hospital Zurich, Clinic for Cardiology, Zurich (Switzerland); Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2014-11-15

    To investigate the accuracy of post-mortem diffusion tensor imaging (DTI) for the detection of myocardial infarction (MI) and to demonstrate the feasibility of helix angle (HA) calculation to study remodelling of myofibre architecture. Cardiac DTI was performed in 26 deceased subjects prior to autopsy for medicolegal reasons. Fractional anisotropy (FA) and mean diffusivity (MD) were determined. Accuracy was calculated on per-segment (AHA classification), per-territory, and per-patient basis, with pathology as reference standard. HAs were calculated and compared between healthy segments and those with MI. Autopsy demonstrated MI in 61/440 segments (13.9 %) in 12/26 deceased subjects. Healthy myocardial segments had significantly higher FA (p < 0.01) and lower MD (p < 0.001) compared to segments with MI. Multivariate logistic regression demonstrated that FA (p < 0.10) and MD (p = 0.01) with the covariate post-mortem time (p < 0.01) predicted MI with an accuracy of 0.73. Analysis of HA distribution demonstrated remodelling of myofibre architecture, with significant differences between healthy segments and segments with chronic (p < 0.001) but not with acute MI (p > 0.05). Post-mortem cardiac DTI enablesdifferentiation between healthy and infarcted myocardial segments by means of FA and MD. HA assessment allows for the demonstration of remodelling of myofibre architecture following chronic MI. (orig.)

  19. Amlodipine and Atorvastatin Improved Hypertensive Cardiac Remodeling through Regulation of MMPs/TIMPs in SHR Rats

    Directory of Open Access Journals (Sweden)

    Jingchao Lu

    2016-06-01

    Full Text Available Background: MMPs/TIMPs system is well known to play important roles in pressure overload-induced cardiac remodeling, and Amlodipine and Atorvastatin have been showed to exert favourable protective effects on cardiovascular disease, however, it is not clear whether Amlodipine and Atorvastatin can improve hypertensive cardiac remodeling and whether the MMPs/TIMPs system is involved. The present study aims to answer these questions. Methods: 36 weeks old male spontaneous hypertension (SHR rats were randomly divided into four groups: 1. SHR control group, 2. Amlodipine alone (10 mg/kg/d group, 3. Atorvastatin alone (10 mg/kg/d group, 4.Combination of Amlodipine and Atorvastatin (10 mg/kg/d for each group. Same gender, weight and age of Wistar-Kyoto (WKY rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The blood pressure and left ventricle mass index were measured. Enzyme activity of MMP-2 and MMP-9 was assessed with Gelatin zymography. MMP-2, MMP-9, TIMP-1 and TIMP-2 mRNA and protein expression was studied by RT-PCR and Western blot. Single factor ANOVA and LSD-t test were used in statistical analysis. Results: Treatment with Amlodipine alone or combination with atorvastatin significantly decreased blood pressure, left ventricle mass index in SHR rats (P Conclusion: Amlodipine and Atorvastatin could improve ventricular remodeling in SHR rats through intervention with the imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 system.

  20. MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.

    Science.gov (United States)

    Guedes, Elaine Castilho; França, Gustavo Starvaggi; Lino, Caroline Antunes; Koyama, Fernanda Christtanini; Moreira, Luana do Nascimento; Alexandre, Juliana Gomes; Barreto-Chaves, Maria Luiza M; Galante, Pedro Alexandre Favoretto; Diniz, Gabriela Placoná

    2016-08-01

    Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature. To address this question, male C57Bl/6 mice were fed with a low fat (LF) diet or two HF diets, containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides, and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart. HF45% diet for 10 and 20 weeks changed the abundance of 64 and 26 miRNAs in the heart, respectively. On the other hand, HF60% diet for 10 and 20 weeks altered the abundance of 27 and 88 miRNAs in the heart, respectively. Bioinformatics analysis indicated that insulin signaling pathway was overrepresented in response to HF diet. An inverse correlation was observed between cardiac levels of GLUT4 and miRNA-29c. Similarly, we found an inverse correlation between expression of GSK3β and the expression of miRNA-21a-3p, miRNA-29c-3p, miRNA-144-3p, and miRNA-195a-3p. In addition, miRNA-1 overexpression prevented cardiomyocyte hypertrophy. Taken together, our results revealed differentially expressed miRNA signatures in the heart in response to different HF diets. J. Cell. Physiol. 231: 1771-1783, 2016. © 2015 Wiley Periodicals, Inc. PMID:26638879

  1. Relationship Between Reverse Remodeling and Cardiopulmonary Exercise Capacity in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Mastenbroek, Mirjam H; Sant, Jetske Van't; Versteeg, Henneke;

    2016-01-01

    BACKGROUND: Studies on the relationship between left ventricular reverse remodeling and cardiopulmonary exercise capacity in heart failure patients undergoing cardiac resynchronization therapy (CRT) are scarce and inconclusive. METHODS AND RESULTS: Eighty-four patients with a 1st-time CRT......-defibrillator (mean age 65 ± 11; 73% male) underwent echocardiography and cardiopulmonary exercise testing (CPX) before implantation (baseline) and 6 months after implantation. At baseline, patients also completed a set of questionnaires measuring mental and physical health. The association between echocardiographic...... echocardiographic responders showed improvements in ventilatory efficiency during follow-up. Multivariable repeated measures analyses revealed that, besides reverse remodeling, New York Heart Association functional class II and good patient-reported health status before implantation were the most important...

  2. Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.

    Directory of Open Access Journals (Sweden)

    Luca Carnevali

    Full Text Available In humans, variants of the fat mass and obesity associated (FTO gene have recently been associated with obesity. However, the physiological function of FTO is not well defined. Previous investigations in mice have linked FTO deficiency to growth retardation, loss of white adipose tissue, increased energy metabolism and enhanced systemic sympathetic activation. In this study we investigated for the first time the effects of global knockout of the mouse FTO gene on cardiac function and its autonomic neural regulation. ECG recordings were acquired via radiotelemetry in homozygous knockout (n = 12 and wild-type (n = 8 mice during resting and stress conditions, and analyzed by means of time- and frequency-domain indexes of heart rate variability. In the same animals, cardiac electrophysiological properties (assessed by epicardial mapping and structural characteristics were investigated. Our data indicate that FTO knockout mice were characterized by (i higher heart rate values during resting and stress conditions, (ii heart rate variability changes (increased LF to HF ratio, (iii larger vulnerability to stress-induced tachyarrhythmias, (iv altered ventricular repolarization, and (v cardiac hypertrophy compared to wild-type counterparts. We conclude that FTO deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart.

  3. Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

    Directory of Open Access Journals (Sweden)

    Nataly Lino Izeli

    2016-04-01

    Full Text Available Abstract Background: Numerous studies show the benefits of exercise training after myocardial infarction (MI. Nevertheless, the effects on function and remodeling are still controversial. Objectives: To evaluate, in patients after (MI, the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR. Methods: 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG, 18; and control group (CG, 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR, exercise test, and CMR were conducted at baseline and follow-up. Results: The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01, and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001. There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001. There was a statistically significant decrease in the TG left ventricular mass (LVmass (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032. There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015. Conclusions: Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction.

  4. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Science.gov (United States)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  5. Cardiac remodeling following percutaneous mitral valve repair. Initial results assessed by cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Radunski, U.K [University Heart Center, Hamburg (Germany). Cardiology; Franzen, O. [Rigshospitalet, Copenhagen (Denmark). Cardiology; Barmeyer, A. [Klinikum Dortmund (Germany). Kardiologie; and others

    2014-10-15

    Percutaneous mitral valve repair with the MitraClip device (Abbott Vascular, Redwood City, California, USA) is a novel therapeutic option in patients with mitral regurgitation. This study evaluated the feasibility of cardiac volume measurements by cardiovascular magnetic resonance imaging (CMR) to assess reverse myocardial remodeling in patients after MitraClip implantation. 12 patients underwent CMR at baseline (BL) before and at 6 months follow-up (FU) after MitraClip implantation. Cine-CMR was performed in short- and long-axes for the assessment of left ventricular (LV), right ventricular (RV) and left atrial (LA) volumes. Assessment of endocardial contours was not compromised by the device-related artifact. No significant differences in observer variances were observed for LV, RV and LA volume measurements between BL and FU. LV end-diastolic (median 127 [IQR 96-150] vs. 112 [86-150] ml/m{sup 2}; p=0.03) and LV end-systolic (82 [54-91] vs. 69 [48-99] ml/m{sup 2}; p=0.03) volume indices decreased significantly from BL to FU. No significant differences were found for RV end-diastolic (94 [75-103] vs. 99 [77-123] ml/m{sup 2}; p=0.91), RV end-systolic (48 [42-80] vs. 51 [40-81] ml/m{sup 2}; p=0.48), and LA (87 [55-124] vs. 92 [48-137]R ml/m{sup 2}; p=0.20) volume indices between BL and FU. CMR enables the assessment of cardiac volumes in patients after MitraClip implantation. Our CMR findings indicate that percutaneous mitral valve repair results in reverse LV but not in RV or LA remodeling.

  6. ATP-sensitive K+ channel knockout induces cardiac proteome remodeling predictive of heart disease susceptibility.

    Science.gov (United States)

    Arrell, D Kent; Zlatkovic, Jelena; Kane, Garvan C; Yamada, Satsuki; Terzic, Andre

    2009-10-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (K(ATP)) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode consequences of Kir6.2 K(ATP) channel pore deletion. Differential two-dimensional gel electrophoresis reproducibly resolved >800 protein species from hearts of asymptomatic wild-type and Kir6.2-knockout counterparts. K(ATP) channel ablation remodeled the cardiac proteome, significantly altering 71 protein spots, from which 102 unique identities were assigned following hybrid linear ion trap quadrupole-Orbitrap tandem mass spectrometry. Ontological annotation stratified the K(ATP) channel-dependent protein cohort into a predominant bioenergetic module (63 resolved identities), with additional focused sets representing signaling molecules (6), oxidoreductases (8), chaperones (6), and proteins involved in catabolism (6), cytostructure (8), and transcription and translation (5). Protein interaction mapping, in conjunction with expression level changes, localized a K(ATP) channel-associated subproteome within a nonstochastic scale-free network. Global assessment of the K(ATP) channel deficient environment verified the primary impact on metabolic pathways and revealed overrepresentation of markers associated with cardiovascular disease. Experimental imposition of graded stress precipitated exaggerated structural and functional myocardial defects in the Kir6.2-knockout, decreasing survivorship and validating the forecast of disease susceptibility. Proteomic cartography thus provides an integral view of molecular remodeling in the heart induced by K(ATP) channel deletion, establishing a

  7. Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

    Energy Technology Data Exchange (ETDEWEB)

    Sofia, Renato Rodrigues [Programa de Pós-graduação em Ciências da Reabilitação - Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Serra, Andrey Jorge, E-mail: andreyserra@gmail.com; Silva, Jose Antonio Jr [Programa de Pós-graduação em Ciências da Reabilitação - Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Antonio, Ednei Luiz [Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Manchini, Martha Trindade [Programa de Pós-graduação em Ciências da Reabilitação - Universidade Nove de Julho (Uninove), São Paulo, SP (Brazil); Oliveira, Fernanda Aparecida Alves de [Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Teixeira, Vicente Paulo Castro [Departamento de Patologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil); Tucci, Paulo José Ferreira [Departamento de Cardiologia - Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-08-15

    Gender can influence post-infarction cardiac remodeling. To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

  8. Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

    International Nuclear Information System (INIS)

    Gender can influence post-infarction cardiac remodeling. To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function

  9. Effect of carvedilol on cardiac function and left ventricular remodeling in rats after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    张军; 贾国良; 王海昌

    2003-01-01

    Objective: To observe the effect of carvedilol injection on left ventricular function and collagen remodeling in rat with myocardial infarction. Methods: Sixty rats with a model of myocardial infarction were randomly divided into nine groups. The rats of therapeutical group were treated with carvedilol injection (2 mg/d intraperitoneal injection) and/or captopil (2 g/L drinking water). Acute myocardial infarction (AMI) group did not receive drug treatment. The animals were sacrificed at 4 weeks and 8 weeks after coronary artery ligation. The levels of plasma angiotensin Ⅱ and plasma aldosterone and left ventricle function were determined at different time. The collagen content and the ratio of type I and Ⅲ collagen of noninfarcted area were also assessed. Results: Compared with AMI group, the levels of plasma and myocardium angiotensin Ⅱ and plasma aldosterone in both carvedilol and captopil group decreased at the eighth week (P<0.05). In addition, carvedilol improved systolic and diastolic function (P<0.05). Compared with sham group, both collagen content and the ratio of type Ⅰ/Ⅲ collagen of noninfarcted area increased in AMI4 and AMI8 group (P<0.05). The hydroxyproline levels and the ratio of type Ⅰ/Ⅲ collagen significantly decreased after carvedilol and/or captopil treatment , compared with AMI group at 4 or 8 week (P<0.05). Conclusion: Carvedilol can improve cardiac function after myocardial infarction and has beneficial effect on left ventricular remodeling.

  10. Human relaxin gene expression delivered by bioreducible dendrimer polymer for post-infarct cardiac remodeling in rats.

    Science.gov (United States)

    Lee, Young Sook; Choi, Joung-Woo; Oh, Jung-Eun; Yun, Chae-Ok; Kim, Sung Wan

    2016-08-01

    In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM. PMID:27174688

  11. Mechanical Regulation of Cardiac Development

    Directory of Open Access Journals (Sweden)

    HuseyinCagatayYalcin

    2014-08-01

    Full Text Available Mechanical forces are an essential contributor to and unavoidable component of cardiac formation, both inducing and orchestrating local and global molecular and cellular changes. Experimental animal studies have contributed substantially to understanding the mechanobiology of heart development. More recent integration of high-resolution imaging modalities with computational modeling has greatly improved our quantitative understanding of hemodynamic flow in heart development. Merging these latest experimental technologies with molecular and genetic signaling analysis will accelerate our understanding of the relationships integrating mechanical and biological signaling for proper cardiac formation. These advances will likely be essential for clinically translatable guidance for targeted interventions to rescue malforming hearts and/or reconfigure malformed circulations for optimal performance. This review summarizes our current understanding on the levels of mechanical signaling in the heart and their roles in orchestrating cardiac development.

  12. Cardiac remodeling following percutaneous mitral valve repair - initial results assessed by cardiovascular magnetic resonance imaging

    DEFF Research Database (Denmark)

    Radunski, U K; Franzen, O; Barmeyer, A;

    2014-01-01

    PURPOSE: Percutaneous mitral valve repair with the MitraClip device (Abbott Vascular, Redwood City, California, USA) is a novel therapeutic option in patients with mitral regurgitation. This study evaluated the feasibility of cardiac volume measurements by cardiovascular magnetic resonance imaging...... mitral valve repair results in reverse LV but not in RV or LA remodeling. KEY POINTS: • Volume measurements by cardiovascular magnetic resonance imaging are feasible following percutaneous mitral valve repair despite device-related artifacts.• A significant reduction of left ventricular volume was found...... end-systolic (48 [42 - 80] vs. 51 [40 - 81] ml/m(2); p = 0.48), and LA (87 [55 - 124] vs. 92 [48 - 137] ml/m(2); p = 0.20) volume indices between BL and FU. CONCLUSION: CMR enables the assessment of cardiac volumes in patients after MitraClip implantation. Our CMR findings indicate that percutaneous...

  13. High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats.

    Directory of Open Access Journals (Sweden)

    Tanya M Holloway

    Full Text Available There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P < 0.05, and promoted a 20% (P<0.05 increase in the left ventricular capillary/fibre ratio, an increase in endothelial nitric oxide synthase protein (P<0.05, and a decrease in hypoxia inducible factor 1 alpha protein content (P<0.05. In contrast, HIIT did not decrease existing fibrosis, and HIIT animals displayed a 20% increase in left ventricular mass (P<0.05 and a 20% decrease in cross sectional area (P<0.05. HIIT also increased brain natriuretic peptide by 50% (P<0.05, in the absence of concomitant angiogenesis, strongly suggesting pathological cardiac remodeling. The current data support the longstanding belief in the effectiveness of ET in hypertension. However, HIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease.

  14. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    OpenAIRE

    Zhipeng Zeng; Kunwu Yu; Long Chen; Weihua Li; Hong Xiao; Zhengrong Huang

    2016-01-01

    CD4+CD25+Foxp3+ regulatory T cells (Treg cells) have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI). We hypothesize that the interleukin- (IL-) 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1) attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significant...

  15. Haptoglobin genotype is a determinant of survival and cardiac remodeling after myocardial infarction in diabetic mice

    Directory of Open Access Journals (Sweden)

    Frisch Avi

    2009-06-01

    Full Text Available Abstract Background We have recently demonstrated in man that a functional allelic polymorphism in the Haptoglobin (Hp gene plays a major role in determining survival and congestive heart failure after myocardial infarction (MI. We sought to recapitulate the effect of Hp type on outcomes and cardiac remodeling after MI in transgenic mice. Methods The Hp 2 allele exists only in man. Wild type C57Bl/6 mice carry the Hp 1 allele with high homology to the human Hp 1 allele. We genetically engineered a murine Hp 2 allele and targeted its insertion by homologous recombination to the murine Hp locus to create Hp 2 mice. Diabetes Mellitus (DM was induced with streptozotocin. MI was produced by occlusion of the left anterior descending artery in DM C57Bl/6 mice carrying the Hp 1 or Hp 2 allele. MI size was determined with TTC staining. Left ventricular (LV function and dimensions were assessed by 2-dimensional echocardiography. Results In the absence of DM, Hp 1-1 and Hp 2-2 mice had similar LV dimensions and LV function. MI size was similar in DM Hp 1-1 and 2-2 mice 24 hours after MI (50.2 ± 2.1%and 46.9 ± 5.5%, respectively, p = 0.6. However, DM Hp 1-1 mice had a significantly lower mortality rate than DM Hp 2-2 mice 30 days after MI (HR 0.41, 95% CI (0.19–0.95, p = 0.037 by log rank. LV chamber dimensions were significantly increased in DM Hp 2-2 mice compared to DM Hp 1-1 mice 30 days after MI (0.196 ± 0.01 cm2 vs. 0.163 ± 0.01 cm2, respectively; p = 0.029. Conclusion In DM mice the Hp 2-2 genotype is associated with increased mortality and more severe cardiac remodeling 30 days after MI.

  16. Cell death and serum markers of collagen metabolism during cardiac remodeling in Cavia porcellus experimentally infected with Trypanosoma cruzi.

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    Yagahira E Castro-Sesquen

    Full Text Available We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP and procollagen type III amino-terminal propeptide (PIIINP. Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response predominated throughout the course of infection; IgG1 (Th2 response was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively. These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection.

  17. Cell death and serum markers of collagen metabolism during cardiac remodeling in Cavia porcellus experimentally infected with Trypanosoma cruzi.

    Science.gov (United States)

    Castro-Sesquen, Yagahira E; Gilman, Robert H; Paico, Henry; Yauri, Verónica; Angulo, Noelia; Ccopa, Fredy; Bern, Caryn

    2013-01-01

    We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection. PMID:23409197

  18. Cardiac remodeling during and after renin-angiotensin system stimulation in Cyp1a1-Ren2 transgenic rats

    DEFF Research Database (Denmark)

    Heijnen, Bart Fj; Pelkmans, Leonie Pj; Danser, Ah Jan;

    2013-01-01

    administration of indole-3-carbinol (I3C). Young (four-weeks old) and adult (30-weeks old) IHR were fed I3C for four weeks (leading to systolic BP >200 mmHg). RAS-stimulation was stopped and animals were followed-up for a consecutive period. Cardiac function and geometry was determined echocardiographically and...... the hearts were excised for molecular and immunohistochemical analyses. Echocardiographic studies revealed that four weeks of RAS-stimulation incited a cardiac remodeling process characterized by increased left ventricular (LV) wall thickness, decreased LV volumes, and shortening of the left ventricle...

  19. Increased cardiac myocyte PDE5 levels in human and murine pressure overload hypertrophy cntribute to adverse LV remodeling

    OpenAIRE

    Vandenwijngaert, Sara; Pokreisz, Peter; Hermans, Hadewich; Gillijns, Hilde; Pellens, Marijke; Bax, Noortje A M; Coppiello, Giulia; Oosterlinck, Wouter; Balogh, Agnes; Papp, Zoltan; Bouten, Carlijn V. C.; Bartunek, Jozef; D'Hooge, Jan; Luttun, Aernout; Verbeken, Erik

    2013-01-01

    Background: The intracellular second messenger cGMP protects the heart under pathological conditions. We examined expression of phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, in human and mouse hearts subjected to sustained left ventricular (LV) pressure overload. We also determined the role of cardiac myocyte-specific PDE5 expression in adverse LV remodeling in mice after transverse aortic constriction (TAC). Methodology/Principal Findings: In patients with severe aortic stenosi...

  20. Exogenous nerve growth factor supplementation elevates myocardial immunoreactivity and attenuates cardiac remodeling in pressure-overload rats

    Institute of Scientific and Technical Information of China (English)

    Bing He; and Yuming Li; Fan Ye; Xin Zhou; He Li; Xiaoqing Xun; Xiaoqing Ma; Xudong Liu; Zhihong Wang; Pengxiao Xu

    2012-01-01

    It is postulated that supplementation of exogenous nerve growth factor (NGF) might mediate improvement of the cardiac sympathetic nerve function in heart failure (HF).Local intramuscular injection of NGF near the cardiac sympathetic ganglia could influence the innervation pattern,norepinephrine transporter (NET) gene expression,and improve the cardiac remodeling in experimental HF animals.In this study,we injected NGF into the scalenus medius muscles of Sprague-Dawley rats with abdominal aortic constriction (AC).The nerve innervated pattern,left ventricular morphology,and function following injection in rats with AC were investigated respectively by immunohistochemistry and echocardiography.Levels of mRNA expression of NET,growth associated protein 43 (GAP 43),NGF and its receptors TrkA and p75NTR,and brain natriuretic peptide (BNP) were measured by realtime polymerase chain reaction.The results showed that myocardial NGF mRNA levels were comparable in rats with AC.Short-term supplementation of exogenous NGF raised the myocardial NGF immunoreactivity,but did not cause hyperinnervation and NET mRNA upregulation in the AC rats.Furthermore,myocardial TrkA mRNA was found to be remarkably decreased and p75NTR mRNA was increased.Myocardial TrkA downregulation may play a beneficial effect for avoiding the hyperinnervation,and it is reasonable to postulate that p75NTR can function as an NGF receptor in the absence of TrkA.Interestingly,local NGF administration into the neck muscles near the ganglia could attenuate cardiac remodeling and downregulate BNP mRNA.These results suggest that exogenous NGF can reach the target tissue along the axons anterogradely,and improve the cardiac remodeling.

  1. Effect of Different Styles of Coronary Heart Disease and Its Risk Factors on Cardiac Remodeling and Dysfunction

    Institute of Scientific and Technical Information of China (English)

    Wang Xuelihong; Guo Xuewei; Ma Yushan; Su Shuangshan; Guo Xiangyu

    2006-01-01

    Objectives To evaluate the effect of different styles of coronary heart disease (CHD),different regions of acute myocardial infarction (AMI),its risk factors and branches of coronary stenosis on left ventricular remodeling and dysfunction by applying echocardiography. Methods 251 patients with CHD and 96 patients without CHD (NoCHD) were verified by selective coronary angiography. CHD patients were divided into stable angina pectoris(SAP) 26, unstable angina pectoris(UAP) 53, acute myocardial infarction (AMI) 140 and old myocardial infarction (OMI) 30 based on clinical situation, cTnT, cardiac enzyme and ECG. AMI patients were further divided into subgroups including acute anterior myocardial infarct (Aa,n =53), acute inferior myocardial infarction(Ai, n=54)and Aa+Ai(n=33) based on ECG. Cardiac parameters:end-diastolic interventricular septum thickness (IVSd),end-diastolic left ventricular internal diameter(LVd ),left ventricular mass (LM), end-diastolic left ventricular volume (EDV), end-systolic left ventricular volume (ESV) and left ventricular ejection fraction(LVEF) were measured by ACUSON 128XP/10 echocardiography.Multiples linear regression analyses were performed to test statistical associations between LVEF and the involved branches of coronary stenosis, blood pressure, lipids, glucose and etc after onset of myocardial infarction. Results EDV and ESV were increased and LVEF decreased on patients with AMI,OMI and UAP (P<0.05-0.0001). LM was mainly increased in patients with OMI (P<0.01) and LVd was mainly enlarged in patients with AMI. EF was significantly decreased and EDV, ESV, LM and LVd were remarkably increased in AMI patients with Aa and Aa+Ai. With the multiple linear regression analyses by SPSS software, we found that LVEF was negatively correlated to the involved branches of coronary stenosis as well as to systolic blood pressure after onset of myocardial infarction while there was no significant correlation between LVEF and other factors. LVEF

  2. Remodeling of inhibitory synaptic connections in developing ferret visual cortex

    Directory of Open Access Journals (Sweden)

    Dalva Matthew B

    2010-02-01

    Full Text Available Abstract Background In the visual cortex, as in many other regions of the developing brain, excitatory synaptic connections undergo substantial remodeling during development. While evidence suggests that local inhibitory synapses may behave similarly, the extent and mechanisms that mediate remodeling of inhibitory connections are not well understood. Results Using scanning laser photostimulation in slices of developing ferret visual cortex, we assessed the overall patterns of developing inhibitory and excitatory synaptic connections converging onto individual neurons. Inhibitory synaptic inputs onto pyramidal neurons in cortical layers 2 and 3 were already present as early as postnatal day 20, well before eye opening, and originated from regions close to the recorded neurons. During the ensuing 2 weeks, the numbers of synaptic inputs increased, with the numbers of inhibitory (and excitatory synaptic inputs peaking near the time of eye opening. The pattern of inhibitory inputs refined rapidly prior to the refinement of excitatory inputs. By uncaging the neurotransmtter GABA in brain slices from animals of different ages, we find that this rapid refinement correlated with a loss of excitatory activity by GABA. Conclusion Inhibitory synapses, like excitatory synapses, undergo significant postnatal remodeling. The time course of the remodeling of inhibitory connections correlates with the emergence of orientation tuning in the visual cortex, implicating these rearrangements in the genesis of adult cortical response properties.

  3. Aerobic exercise improves the inflammatory profile correlated with cardiac remodeling and function in chronic heart failure rats

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    Ramiro B. Nunes

    2013-06-01

    Full Text Available OBJECTIVE: The aim of the present study was to evaluate the effect of 8 weeks of aerobic exercise training on cardiac functioning and remodeling and on the plasma levels of inflammatory cytokines in chronic heart failure rats. METHODS: Wistar rats were subjected to myocardial infarction or sham surgery and assigned to 4 groups: chronic heart failure trained (n = 7, chronic heart failure sedentary (n = 6, sham trained (n = 8 and sham sedentary (n = 8. Four weeks after the surgical procedures, the rats were subjected to aerobic training in the form of treadmill running (50 min/day, 5 times per week, 16 m/min. At the end of 8 weeks, the rats were placed under anesthesia, the hemodynamic variables were recorded and blood samples were collected. Cardiac hypertrophy was evaluated using the left ventricular weight/body weight ratio, and the collagen volume fraction was assessed using histology. RESULTS: The chronic heart failure trained group showed a reduction in left ventricular end-diastolic pressure, a lower left ventricular weight/body weight ratio and a lower collagen volume fraction compared with the chronic heart failure sedentary group. In addition, exercise training reduced the plasma levels of TNF-α and IL-6 and increased the plasma level of IL-10. CONCLUSION: An 8-week aerobic exercise training program improved the inflammatory profile and cardiac function and attenuated cardiac remodeling in chronic heart failure rats.

  4. Long Non-Coding RNA Malat-1 Is Dispensable during Pressure Overload-Induced Cardiac Remodeling and Failure in Mice.

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    Tim Peters

    Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules with diverse regulatory functions during embryonic development, normal life, and disease in higher organisms. However, research on the role of lncRNAs in cardiovascular diseases and in particular heart failure is still in its infancy. The exceptionally well conserved nuclear lncRNA Metastasis associated in lung adenocarcinoma transcript 1 (Malat-1 is a regulator of mRNA splicing and highly expressed in the heart. Malat-1 modulates hypoxia-induced vessel growth, activates ERK/MAPK signaling, and scavenges the anti-hypertrophic microRNA-133. We therefore hypothesized that Malat-1 may act as regulator of cardiac hypertrophy and failure during cardiac pressure overload induced by thoracic aortic constriction (TAC in mice.Absence of Malat-1 did not affect cardiac hypertrophy upon pressure overload: Heart weight to tibia length ratio significantly increased in WT mice (sham: 5.78±0.55, TAC 9.79±1.82 g/mm; p<0.001 but to a similar extend also in Malat-1 knockout (KO mice (sham: 6.21±1.12, TAC 8.91±1.74 g/mm; p<0.01 with no significant difference between genotypes. As expected, TAC significantly reduced left ventricular fractional shortening in WT (sham: 38.81±6.53%, TAC: 23.14±11.99%; p<0.01 but to a comparable degree also in KO mice (sham: 37.01±4.19%, TAC: 25.98±9.75%; p<0.05. Histological hallmarks of myocardial remodeling, such as cardiomyocyte hypertrophy, increased interstitial fibrosis, reduced capillary density, and immune cell infiltration, did not differ significantly between WT and KO mice after TAC. In line, the absence of Malat-1 did not significantly affect angiotensin II-induced cardiac hypertrophy, dysfunction, and overall remodeling. Above that, pressure overload by TAC significantly induced mRNA levels of the hypertrophy marker genes Nppa, Nppb and Acta1, to a similar extend in both genotypes. Alternative splicing of Ndrg2 after TAC was apparent in WT (isoform ratio

  5. Interleukin-2/Anti-Interleukin-2 Immune Complex Attenuates Cardiac Remodeling after Myocardial Infarction through Expansion of Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Zhipeng Zeng

    2016-01-01

    Full Text Available CD4+CD25+Foxp3+ regulatory T cells (Treg cells have protective effects in wound healing and adverse ventricular remodeling after myocardial infarction (MI. We hypothesize that the interleukin- (IL- 2 complex comprising the recombinant mouse IL-2/anti-IL-2 mAb (JES6-1 attenuates cardiac remodeling after MI through the expansion of Treg. Mice were subjected to surgical left anterior descending coronary artery ligation and treated with either PBS or IL-2 complex. The IL-2 complex significantly attenuates ventricular remodeling, as demonstrated by reduced infarct size, improved left ventricular (LV function, and attenuated cardiomyocyte apoptosis. The IL-2 complex increased the percentage of CD4+CD25+Foxp3+ Treg cells, which may be recruited to the infarcted heart, and decreased the frequencies of IFN-γ- and IL-17-producing CD4+ T helper (Th cells among the CD4+Foxp3− T cells in the spleen. Furthermore, the IL-2 complex inhibited the gene expression of proinflammatory cytokines as well as macrophage infiltrates in the infarcted myocardium and induced the differentiation of macrophages from M1 to M2 phenotype in border zone of infarcted myocardium. Our studies indicate that the IL-2 complex may serve as a promising therapeutic approach to attenuate adverse remodeling after MI through expanding Treg cells specifically.

  6. Intramyocardial delivery of mesenchymal stem cell-seeded hydrogel preserves cardiac function and attenuates ventricular remodeling after myocardial infarction.

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    Eva Mathieu

    Full Text Available BACKGROUND: To improve the efficacy of bone marrow-derived mesenchymal stem cell (MSC therapy targeted to infarcted myocardium, we investigated whether a self-setting silanized hydroxypropyl methylcellulose (Si-HPMC hydrogel seeded with MSC (MSC+hydrogel could preserve cardiac function and attenuate left ventricular (LV remodeling during an 8-week follow-up study in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDING: Si-HPMC hydrogel alone, MSC alone or MSC+hydrogel were injected into the myocardium immediately after coronary artery ligation in female Lewis rats. Animals in the MSC+hydrogel group showed an increase in cardiac function up to 28 days after MI and a mid-term prevention of cardiac function alteration at day 56. Histological analyses indicated that the injection of MSC+hydrogel induced a decrease in MI size and an increase in scar thickness and ultimately limited the transmural extent of MI. These findings show that intramyocardial injection of MSC+hydrogel induced short-term recovery of ventricular function and mid-term attenuation of remodeling after MI. CONCLUSION/SIGNIFICANCE: These beneficial effects may be related to the specific scaffolding properties of the Si-HPMC hydrogel that may provide the ability to support MSC injection and engraftment within myocardium.

  7. Adenoviral short hairpin RNA therapy targeting phosphodiesterase 5a relieves cardiac remodeling and dysfunction following myocardial infarction

    OpenAIRE

    Li, Longhu; Haider, Husnain Kh; WANG, Linlin; Lu, Gang; Ashraf, Muhammad

    2012-01-01

    We previously showed that treatment with tadalafil, a long-acting phosphodiesterase-5a (PDE5a) inhibitor, effectively prevented adverse left ventricular (LV) remodeling of the infarcted heart. We hypothesized that short-hairpin RNA (shRNA) therapy targeting PDE5a would simulate the effects of pharmacological intervention for treatment of postinfarction LV remodeling and dysfunction. Experimental model of myocardial infarction was developed in female mice by permanent ligation of left coronary...

  8. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    OpenAIRE

    Honghui Li; Dongmei Cui; Feng Zhao; Lijun Huo; Jianmin Hu; Junwen Zeng

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced ...

  9. The solid state environment orchestrates embryonic development and tissue remodeling

    Science.gov (United States)

    Damsky, C. H.; Moursi, A.; Zhou, Y.; Fisher, S. J.; Globus, R. K.

    1997-01-01

    Cell interactions with extracellular matrix and with other cells play critical roles in morphogenesis during development and in tissue homeostasis and remodeling throughout life. Extracellular matrix is information-rich, not only because it is comprised of multifunctional structural ligands for cell surface adhesion receptors, but also because it contains peptide signaling factors, and proteinases and their inhibitors. The functions of these groups of molecules are extensively interrelated. In this review, three primary cell culture models are described that focus on adhesion receptors and their roles in complex aspects of morphogenesis and remodeling: the regulation of proteinase expression by fibronectin and integrins in synovial fibroblasts; the regulation of osteoblast differentiation and survival by fibronectin, and the regulation of trophoblast differentiation and invasion by integrins, cadherins and immunoglobulin family adhesion receptors.

  10. Targeted disruption of the heat shock protein 20–phosphodiesterase 4D (PDE4D interaction protects against pathological cardiac remodelling in a mouse model of hypertrophy

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    Tamara P. Martin

    2014-01-01

    Full Text Available Phosphorylated heat shock protein 20 (HSP20 is cardioprotective. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs and a mouse model of pressure overload mediated hypertrophy, we show that peptide disruption of the HSP20–phosphodiesterase 4D (PDE4D complex results in attenuation of action potential prolongation and protection against adverse cardiac remodelling. The later was evidenced by improved contractility, decreased heart weight to body weight ratio, and reduced interstitial and perivascular fibrosis. This study demonstrates that disruption of the specific HSP20–PDE4D interaction leads to attenuation of pathological cardiac remodelling.

  11. Elasticity of developing cardiac tissue

    Science.gov (United States)

    Majkut, Stephanie; Swift, Joe; Krieger, Christine; Discher, Dennis

    2011-03-01

    Proper development and function of the heart from the tissue to cellular scale depends on a compliant ECM. Here we study the maturation of embryonic cardiac tissue mechanics in parallel with the effects of extracellular mechanics on individual cardiomyocyte function throughout early development. We used micropipette aspiration to measure local and bulk elastic moduli (E) of embryonic avian heart tissue from days 2-12. We observe stiffening of the early heart tube from E = 1 kPa at day 1 to E = 2 kPa at day 4, reaching neonatal values by day 12. Treating heart tubes with blebbistatin led to 30% decrease in E, indicating a significant but partial actomyosin contribution to mechanics at these stages. We performed a proteomic analysis of intact and decellularized 2-4 day heart tubes by mass spectrometry to quantify the ECM present at these stages. Isolated cardiomyocytes from 2-4 day chick embryos were cultured on collagen-coated PA gels of various stiffnesses. Beating magnitude was modulated by substrates with E = 1-2 kPa, similar to physiological E at those stages.

  12. iPSC-derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium.

    Science.gov (United States)

    Ja, Kp Myu Mia; Miao, Qingfeng; Zhen Tee, Nicole Gui; Lim, Sze Yun; Nandihalli, Manasi; J A Ramachandra, Chrishan; Mehta, Ashish; Shim, Winston

    2016-02-01

    We investigate the effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived progenitors and cardiomyocytes into acutely infarcted myocardium in severe combined immune deficiency mice. A total of 2 × 10(5) progenitors, cardiomyocytes or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Myocardial function was assessed at 2-week and 4-week post-infarction by using echocardiography and pressure-volume catheterization. Early myocardial remodelling was observed at 2-week with echocardiography derived stroke volume (SV) in saline (20.45 ± 7.36 μl, P EDV: 23.24 ± 5.01 μl, P EDV: 26.45 ± 5.69 μl, P EDV: 15.26 ± 2.96 μl; ESV: 8.41 ± 2.94 μl). In contrast, cardiac progenitors (EDV: 20.09 ± 7.76 μl; ESV: 13.98 ± 6.74 μl) persistently protected chamber geometry against negative cardiac remodelling. Similarly, as compared to sham control (54.64 ± 11.37%), LV ejection fraction was preserved in progenitor group from 2-(38.68 ± 7.34%) to 4-week (39.56 ± 13.26%) while cardiomyocyte (36.52 ± 11.39%, P < 0.05) and saline (35.34 ± 11.86%, P < 0.05) groups deteriorated early at 2-week. Improvements of myocardial function in the progenitor group corresponded to increased vascularization (16.12 ± 1.49/mm(2) to 25.48 ± 2.08/mm(2) myocardial tissue, P < 0.05) and coincided with augmented networking of cardiac telocytes in the interstitial space of infarcted zone. PMID:26612359

  13. Development of Bone Remodeling Model for Spaceflight Bone Physiology Analysis

    Science.gov (United States)

    Pennline, James A.; Werner, Christopher R.; Lewandowski, Beth; Thompson, Bill; Sibonga, Jean; Mulugeta, Lealem

    2015-01-01

    Current spaceflight exercise countermeasures do not eliminate bone loss. Astronauts lose bone mass at a rate of 1-2% a month (Lang et al. 2004, Buckey 2006, LeBlanc et al. 2007). This may lead to early onset osteoporosis and place the astronauts at greater risk of fracture later in their lives. NASA seeks to improve understanding of the mechanisms of bone remodeling and demineralization in 1g in order to appropriately quantify long term risks to astronauts and improve countermeasures. NASA's Digital Astronaut Project (DAP) is working with NASA's bone discipline to develop a validated computational model to augment research efforts aimed at achieving this goal.

  14. Triterpenoid dihydro-CDDO-trifluoroethyl amide protects against maladaptive cardiac remodeling and dysfunction in mice: a critical role of Nrf2.

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    Yifan Xing

    Full Text Available BACKGROUND AND AIMS: Nuclear factor E2-related factor 2 (Nrf2 appears to be an attractive therapeutic target for the treatment of cardiac disease. We investigated whether a synthetic triterpenoid derivative of dihydro-CDDO-trifluoroethylamide (dh404, a novel Nrf2 activator, protects against pathological cardiac responses to hemodynamic stress in mice. METHODS: Cardiac maladaptive remodeling and dysfunction were established by transverse aortic constriction (TAC in mice. Hypertrophic growth of rat neonatal cardiomyocytes was induced by angiotensin II (Ang II. Cell death of rat neonatal cardiomyocytes was induced with hydrogen peroxide (H₂O₂. Cellular proliferation of rat neonatal cardiac fibroblasts was induced by Ang II, norepinephrine (NE and phenylephrine (PE. Protein expression was assessed by immunochemical staining and Western blots. Gene expression was determined by real time reverse transcription-polymerase chain reaction (Q-PCR. RESULTS: TAC suppressed myocardial Nrf2 expression, increased myocardial 4-hydroxy-2-nonenal and 8-hydroxydeoxyguanosine levels, and induced cardiac hypertrophy, fibrosis and apoptosis, and overt heart failure and death in mice. Administration of dh404 inhibited the pathological cardiac remodeling and dysfunction, and reduced the mortality. Moreover, dhd404 elevated myocardial levels of Nrf2 and Nrf2 nuclear translocation with a dramatic suppression of the oxidative stress in the heart. Dh404 inhibited hypertrophic growth and death in primary culture of rat neonatal cardiomyocytes and suppressed proliferation in primary culture of rat neonatal cardiac fibroblasts. However, these effects of dh404 were blunted by knocking down of Nrf2. CONCLUSION: These findings demonstrate that dh404 prevents pathological cardiac remodeling and dysfunction by activating Nrf2, indicating a therapeutic potential of dh404 for cardiac disease.

  15. Carbon monoxide pollution promotes cardiac remodeling and ventricular arrhythmia in healthy rats.

    OpenAIRE

    Andre, Lucas; Boissière, Julien; Reboul, Cyril; Perrier, Romain; Zalvidea, Santiago; Meyer, Gregory; Thireau, Jérôme; Tanguy, Stéphane; Bideaux, Patrice; Hayot, Maurice; Boucher, François; Obert, Philippe; Cazorla, Olivier; Richard, Sylvain

    2010-01-01

    RATIONALE: Epidemiologic studies associate atmospheric carbon monoxide (CO) pollution with adverse cardiovascular outcomes and increased cardiac mortality risk. However, there is a lack of data regarding cellular mechanisms in healthy individuals. OBJECTIVES: To investigate the chronic effects of environmentally relevant CO levels on cardiac function in a well-standardized healthy animal model. METHODS: Wistar rats were exposed for 4 weeks to filtered air (CO < 1 ppm) or air enriched with CO ...

  16. BMP-2 Is Involved in Scleral Remodeling in Myopia Development.

    Directory of Open Access Journals (Sweden)

    Honghui Li

    Full Text Available The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2 expression in the sclera of guinea pigs with lens-induced myopia (LIM and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM synthesis in human scleral fibroblasts (HSFs cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1. Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia.

  17. BMP-2 Is Involved in Scleral Remodeling in Myopia Development

    Science.gov (United States)

    Li, Honghui; Cui, Dongmei; Zhao, Feng; Huo, Lijun; Hu, Jianmin; Zeng, Junwen

    2015-01-01

    The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1). Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG) and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia. PMID:25965995

  18. TWEAK-Fn14 cytokine-receptor axis: a new player of myocardial remodeling and cardiac failure

    Directory of Open Access Journals (Sweden)

    Tatyana eNovoyatleva

    2014-02-01

    Full Text Available Tumor necrosis factor (TNF has been firmly established as a pathogenic factor in heart failure, a significant socio-economic burden. In this review we will explore the role of other members of the TNF/TNF receptor superfamily (TNFSF/TNFRSF in cardiovascular diseases (CVDs focusing on TWEAK and its receptor Fn14, new players in myocardial remodeling and heart failure. The TWEAK/Fn14 pathway controls a variety of cellular activities such as proliferation, differentiation and apoptosis and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with CVDs. Furthermore, it has recently been shown that the TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy and that deletion of Fn14 receptor protects from right heart fibrosis and dysfunction. We discuss the potential use of the TWEAK/Fn14 axis as biomarker for CVDs as well as therapeutic target for future treatment of human heart failure based on supporting data from animal models and in vitro studies. Collectively, existing data strongly suggest the TWEAK/Fn14 axis as a potential new therapeutic target for achieving cardiac protection in patients with CVDs.

  19. Hydrogen Sulfide Mitigates Cardiac Remodeling During Myocardial Infarction via Improvement of Angiogenesis

    Directory of Open Access Journals (Sweden)

    Natia Qipshidze, Naira Metreveli, Paras K. Mishra, David Lominadze, Suresh C. Tyagi

    2012-01-01

    Full Text Available Exogenous hydrogen sulfide (H2S leads to down-regulation of inflammatory responses and provides myocardial protection during acute ischemia/reperfusion injury; however its role during chronic heart failure (CHF due to myocardial infarction (MI is yet to be unveiled. We previously reported that H2S inhibits antiangiogenic factors such, as endostatin and angiostatin, but a little is known about its effect on parstatin (a fragment of proteinase-activated receptor-1, PAR-1. We hypothesize that H2S inhibits parstatin formation and promotes VEGF activation, thus promoting angiogenesis and significantly limiting the extent of MI injury. To verify this hypothesis MI was created in 12 week-old male mice by ligation of left anterior descending artery (LAD. Sham surgery was performed except LAD ligation. After the surgery mice were treated with sodium hydrogen sulfide (30 μmol/l NaHS, a donor for H2S, in drinking water for 4 weeks. The LV tissue was analyzed for VEGF, flk-1 and flt-1, endostatin, angiostatin and parstatin. The expression of VEGF, flk-1 and flt-1 were significantly increased in treated mice while the level of endostatin, angiostatin and parstatin were decreased compared to in untreated mice. The echocardiography in mice treated with H2S showed the improvement of heart function compared to in untreated mice. The X-ray and Doppler blood flow measurements showed enhancement of cardiac-angiogenesis in mice treated with H2S. This observed cytoprotection was associated with an inhibition of anti-angiogenic proteins and stimulation of angiogenic factors. We established that administration of H2S at the time of MI ameliorated infarct size and preserved LV function during development of MI in mice. These results suggest that H2S is cytoprotective and angioprotective during evolution of MI.

  20. Multiscale characterization of cardiac remodeling induced by intrauterine growth restriction, at organ, cellular and subcellular level

    OpenAIRE

    González Tendero, Anna

    2014-01-01

    Tesi realitzada a l'Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) INTRODUCTION: Intrauterine growth restriction (IUGR) due to placental insufficiency affects up to 7-10% of pregnancies and is a major cause of perinatal mortality and long term morbidity. IUGR results in low birth weight, which is associated with increased risk of cardiovascular mortality in adulthood, and is thought to be mediated by fetal cardiovascular programming. IUGR fetuses show signs of cardiac s...

  1. ATP-Sensitive K+ Channel Knockout Induces Cardiac Proteome Remodeling Predictive of Heart Disease Susceptibility

    OpenAIRE

    Arrell, D. Kent; Zlatkovic, Jelena; Kane, Garvan C; Yamada, Satsuki; Terzic, Andre

    2009-01-01

    Forecasting disease susceptibility requires detection of maladaptive signatures prior to onset of overt symptoms. A case-in-point are cardiac ATP-sensitive K+ (KATP) channelopathies, for which the substrate underlying disease vulnerability remains to be identified. Resolving molecular pathobiology, even for single genetic defects, mandates a systems platform to reliably diagnose disease predisposition. High-throughput proteomic analysis was here integrated with network biology to decode conse...

  2. Myocardial stress and hypertrophy: a complex interface between biophysics and cardiac remodeling

    OpenAIRE

    Grossman, William; Paulus, Walter J.

    2013-01-01

    Pressure and volume overload results in concentric and eccentric hypertrophy of cardiac ventricular chambers with, respectively, parallel and series replication of sarcomeres. These divergent patterns of hypertrophy were related 40 years ago to disparate wall stresses in both conditions, with systolic wall stress eliciting parallel replication of sarcomeres and diastolic wall stress, series replication. These observations are relevant to clinical practice, as they relate to the excessive hype...

  3. High Molecular Weight Fibroblast Growth Factor-2 in the Human Heart Is a Potential Target for Prevention of Cardiac Remodeling

    Science.gov (United States)

    Santiago, Jon-Jon; McNaughton, Leslie J.; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E.; Fandrich, Robert R.; Wigle, Jeffrey T.; Freed, Darren H.; Arora, Rakesh C.; Kardami, Elissavet

    2014-01-01

    Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious

  4. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    LENUS (Irish Health Repository)

    Phelan, Dermot

    2012-11-01

    In asymptomatic subjects B-type natriuretic peptide (BNP) is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM) alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS) and peripheral serum from patients with low (n = 14) and high BNP (n = 27). Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001). CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008), CITP (r = 0.35, p = 0.03) and PIIINP (r = 0.35, p = 0.001), and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002), IL-6 (r = 0.35, p = 0.04), and IL-8 (r = 0.54, p<0.001). The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007), TNF-α (3.2±0.5 versus 3.7±1.1, p = 003), IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02) and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04), and greater left ventricular mass index (97±20 versus 118±26 g\\/m(2), p = 0.03) and left atrial volume index (18±2 versus 21±4, p = 0.008). Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  5. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    Jon-Jon Santiago

    Full Text Available Fibroblast growth factor 2 (FGF-2 is a multifunctional protein synthesized as high (Hi- and low (Lo- molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD and 68% (±25 SD of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2 reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes

  6. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes.

    Directory of Open Access Journals (Sweden)

    Dermot Phelan

    Full Text Available In asymptomatic subjects B-type natriuretic peptide (BNP is associated with adverse cardiovascular outcomes even at levels well below contemporary thresholds used for the diagnosis of heart failure. The mechanisms behind these observations are unclear. We examined the hypothesis that in an asymptomatic hypertensive population BNP would be associated with sub-clinical evidence of cardiac remodeling, inflammation and extracellular matrix (ECM alterations. We performed transthoracic echocardiography and sampled coronary sinus (CS and peripheral serum from patients with low (n = 14 and high BNP (n = 27. Peripheral BNP was closely associated with CS levels (r = 0.92, p<0.001. CS BNP correlated significantly with CS levels of markers of collagen type I and III turnover including: PINP (r = 0.44, p = 0.008, CITP (r = 0.35, p = 0.03 and PIIINP (r = 0.35, p = 0.001, and with CS levels of inflammatory cytokines including: TNF-α (r = 0.49, p = 0.002, IL-6 (r = 0.35, p = 0.04, and IL-8 (r = 0.54, p<0.001. The high BNP group had greater CS expression of fibro-inflammatory biomarkers including: CITP (3.8±0.7 versus 5.1±1.9, p = 0.007, TNF-α (3.2±0.5 versus 3.7±1.1, p = 003, IL-6 (1.9±1.3 versus 3.4±2.7, p = 0.02 and hsCRP (1.2±1.1 versus 2.4±1.1, p = 0.04, and greater left ventricular mass index (97±20 versus 118±26 g/m(2, p = 0.03 and left atrial volume index (18±2 versus 21±4, p = 0.008. Our data provide insight into the mechanisms behind the observed negative prognostic impact of modest elevations in BNP and suggest that in an asymptomatic hypertensive cohort a peripheral BNP measurement may be a useful marker of an early, sub-clinical pathological process characterized by cardiac remodeling, inflammation and ECM alterations.

  7. Sirtuin1-p53, forkhead box O3a, p38 and post-infarct cardiac remodeling in the spontaneously diabetic Goto-Kakizaki rat

    Directory of Open Access Journals (Sweden)

    Kytö Ville

    2010-01-01

    Full Text Available Abstract Background Diabetes is associated with changes in myocardial stress-response pathways and is recognized as an independent risk factor for cardiac remodeling. Using spontaneously diabetic Goto Kakizaki rats as a model of type 2 DM we investigated whether post-translational modifications in the Akt - FOXO3a pathway, Sirt1 - p53 pathway and the mitogen activated protein kinase p38 regulator are involved in post-infarct cardiac remodeling Methods Experimental myocardial infarction (MI was induced by left anterior descending coronary artery ligation in spontaneously diabetic Goto-Kakizaki rats and non-diabetic Wistar controls. Cardiac function was studied by echocardiography. Myocardial hypertrophy, cardiomyocyte apoptosis and cardiac fibrosis were determined histologically 12 weeks post MI or Sham operation. Western blotting was used to study Caspase-3, Bax, Sirt1, acetylation of p53 and phosphorylation of p38, Akt and FOXO3a. Electrophoretic mobility shift assay was used to assess FOXO3a activity and its nuclear localization. Results Post-infarct heart failure in diabetic GK rats was associated with pronounced cardiomyocyte hypertrophy, increased interstitial fibrosis and sustained cardiomyocyte apoptosis as compared with their non-diabetic Wistar controls. In the GK rat myocardium, Akt- and FOXO3a-phosphorylation was decreased and nuclear localization of FOXO3a was increased concomitantly with increased PTEN protein expression. Furthermore, increased Sirt1 protein expression was associated with decreased p53 acetylation, and phosphorylation of p38 was increased in diabetic rats with MI. Conclusions Post-infarct heart failure in diabetic GK rats was associated with more pronounced cardiac hypertrophy, interstitial fibrosis and sustained cardiomyocyte apoptosis as compared to their non-diabetic controls. The present study suggests important roles for Akt-FOXO3a, Sirt1 - p53 and p38 MAPK in the regulation of post-infarct cardiac remodeling

  8. (Prorenin receptor triggers distinct angiotensin II-independent extracellular matrix remodeling and deterioration of cardiac function.

    Directory of Open Access Journals (Sweden)

    Anne-Mari Moilanen

    Full Text Available BACKGROUND: Activation of the renin-angiotensin-system (RAS plays a key pathophysiological role in heart failure in patients with hypertension and myocardial infarction. However, the function of (prorenin receptor ((PRR is not yet solved. We determined here the direct functional and structural effects of (PRR in the heart. METHODOLOGY/PRINCIPAL FINDINGS: (PRR was overexpressed by using adenovirus-mediated gene delivery in normal adult rat hearts up to 2 weeks. (PRR gene delivery into the anterior wall of the left ventricle decreased ejection fraction (P<0.01, fractional shortening (P<0.01, and intraventricular septum diastolic and systolic thickness, associated with approximately 2-fold increase in left ventricular (PRR protein levels at 2 weeks. To test whether the worsening of cardiac function and structure by (PRR gene overexpression was mediated by angiotensin II (Ang II, we infused an AT(1 receptor blocker losartan via osmotic minipumps. Remarkably, cardiac function deteriorated in losartan-treated (PRR overexpressing animals as well. Intramyocardial (PRR gene delivery also resulted in Ang II-independent activation of extracellular-signal-regulated kinase1/2 phosphorylation and myocardial fibrosis, and the expression of transforming growth factor-β1 and connective tissue growth factor genes. In contrast, activation of heat shock protein 27 phosphorylation and apoptotic cell death by (PRR gene delivery was Ang II-dependent. Finally, (PRR overexpression significantly increased direct protein-protein interaction between (PRR and promyelocytic zinc-finger protein. CONCLUSIONS/SIGNIFICANCE: These results indicate for the first time that (PRR triggers distinct Ang II-independent myocardial fibrosis and deterioration of cardiac function in normal adult heart and identify (PRR as a novel therapeutic target to optimize RAS blockade in failing hearts.

  9. Functional suppression of Kcnq1 leads to early sodium channel remodelling and cardiac conduction system dysmorphogenesis

    Czech Academy of Sciences Publication Activity Database

    De la Rosa, A. J.; Domínguez, J. N.; Sedmera, D.; Šaňková, Barbora; Hove-Madsen, L.; Franco, D.; Aránega, A. E.

    2013-01-01

    Roč. 98, č. 3 (2013), s. 504-514. ISSN 0008-6363 R&D Projects: GA ČR(CZ) GA304/08/0615; GA ČR(CZ) GAP302/11/1308; GA ČR(CZ) GD204/09/H084; GA ČR(CZ) GA13-12412S Institutional research plan: CEZ:AV0Z50110509 Institutional support : RVO:67985823 Keywords : ion channels * Long-QT syndrome * sudden death * cardiac hypertrophy Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 5.808, year: 2013

  10. Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis.

    Science.gov (United States)

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  11. High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity

    Directory of Open Access Journals (Sweden)

    Fernando Martins

    2015-01-01

    Full Text Available AbstractBackground:Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity.Objective:To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet.Methods:Sixteen Wistar rats were used, distributed into two groups, the control (C group, treated with isocaloric diet (2.93 kcal/g and an obese (OB group, treated with high-fat diet (3.64 kcal/g. The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed.Results:High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained.Conclusion:It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

  12. Hypoxic remodelling of Ca{sup 2+} stores does not alter human cardiac myofibroblast invasion

    Energy Technology Data Exchange (ETDEWEB)

    Riches, K.; Hettiarachchi, N.T.; Porter, K.E. [Leeds Institute for Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT (United Kingdom); Peers, C., E-mail: c.s.peers@leeds.ac.uk [Leeds Institute for Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT (United Kingdom)

    2010-12-17

    Research highlights: {yields} Bradykinin promotes migration and proliferation of myofibroblasts. {yields} Such activity is Ca{sup 2+}-dependent and occurs under hypoxic conditions. {yields} Hypoxia increased myofibroblast Ca{sup 2+} stores but not influx evoked by bradykinin. {yields} Myofibroblast migration and proliferation was unaffected by hypoxia. -- Abstract: Cardiac fibroblasts are the most abundant cell type in the heart, and play a key role in the maintenance and repair of the myocardium following damage such as myocardial infarction by transforming into a cardiac myofibroblast (CMF) phenotype. Repair occurs through controlled proliferation and migration, which are Ca{sup 2+} dependent processes, and often requires the cells to operate within a hypoxic environment. Angiotensin converting enzyme (ACE) inhibitors reduce infarct size through the promotion of bradykinin (BK) stability. Although CMF express BK receptors, their activity under the reduced O{sub 2} conditions that occur following infarct are entirely unexplored. Using Fura-2 microfluorimetry on primary human CMF, we found that hypoxia significantly increased the mobilisation of Ca{sup 2+} from intracellular stores in response to BK whilst capacitative Ca{sup 2+} entry (CCE) remained unchanged. The enhanced store mobilisation was due to a striking increase in CMF intracellular Ca{sup 2+}-store content under hypoxic conditions. However, BK-induced CMF migration or proliferation was not affected following hypoxic exposure, suggesting that Ca{sup 2+} influx rather than mobilisation is of primary importance in CMF migration and proliferation.

  13. Relationship of cardiac arrhythmias to myocar- dial remodeling and expression of adhesion molecules in patients with mitral valve prolapse

    Directory of Open Access Journals (Sweden)

    A.V. Yagoda

    Conclusion. Myocardial remodeling and dysregulation of cell adhesion proteins are recorded in young patients with MVP and arrhythmias. Relaionship of severity of arrhythmic syndrome to myocardial remodeling and VCAM-1 level was revealed.

  14. Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions and cardiac remodeling

    International Nuclear Information System (INIS)

    To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy. (author)

  15. The muscle-enriched gene SYNPO2L is associated with cardiac remodeling%新基因SYNPO2L参与心肌重构

    Institute of Scientific and Technical Information of China (English)

    王晓建; 甄一松; 王继征; 苏明; 祝领; 王长鑫; 俞莉萍; 刘继斌; 惠汝太

    2012-01-01

    目的 肌肉富集表达基因在心肌重构的发生发展中发挥重要的作用.为了深入理解心肌重构的分子机制、为临床提供治疗和干预的靶点,我们需要寻找参与心肌重构的新基因.方法和结果 我们使用自主研发的CardiacScan对多个人源组织表达谱数据库进行扫描,发现了一个新的肌肉富集表达基因——SYNPO2L.RT-PCR显示,SYNPO2L在小鼠的心脏和骨骼肌高表达.实时荧光定量PCR显示,在跑步训练诱导的小鼠生理性心肌重构模型中,SYNPO2L的表达下降为对照组的0.6倍(P<0.05).在主动脉缩窄手术诱导的病理性心肌重构中,SYNPO2L的表达逐渐升高,并在术后9周(心功能失代偿阶段)升高为对照组的2.4倍(P<0.0001).结论 SYNPO2L是一个新的在肌肉富集表达的基因,参与了多种不同形式的心肌重构过程,可能在心肌重构中发挥重要的作用.%Purpose Muscle-enriched gene play an improtant role in the development of cardiac remodeling and heart failure. Up to date, however, the number of muscle-enriched gene is limited. Therefore, we need to clone more muscle-enriched genes. Methods and Results To explore novel muscle-enriched genes, we scaned three human multiple-tissue transcriptional databases using self-developed program Card iacScan. SYNPO2L was identified as novlc muslce-enriched gene. Real-time PCR analysis demonstrated that expression of SYNPO2L was down-regulated by 0.6 fold (P<0.0S) in physiological cardiac hypertrophy induced by treadmill training, but up-regulated by 2.4 fold(P<0.0001) in heart failure induced by transverse aortic constriction surgery. Conclusion SYNPO2L is a novle muscle-enriched gene which is involved in cardiac remodeling.

  16. Cardiac-Restricted IGF-1Ea Overexpression Reduces the Early Accumulation of Inflammatory Myeloid Cells and Mediates Expression of Extracellular Matrix Remodelling Genes after Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Enrique Gallego-Colon

    2015-01-01

    Full Text Available Strategies to limit damage and improve repair after myocardial infarct remain a major therapeutic goal in cardiology. Our previous studies have shown that constitutive expression of a locally acting insulin-like growth factor-1 Ea (IGF-1Ea propeptide promotes functional restoration after cardiac injury associated with decreased scar formation. In the current study, we investigated the underlying molecular and cellular mechanisms behind the enhanced functional recovery. We observed improved cardiac function in mice overexpressing cardiac-specific IGF-1Ea as early as day 7 after myocardial infarction. Analysis of gene transcription revealed that supplemental IGF-1Ea regulated expression of key metalloproteinases (MMP-2 and MMP-9, their inhibitors (TIMP-1 and TIMP-2, and collagen types (Col 1α1 and Col 1α3 in the first week after injury. Infiltration of inflammatory cells, which direct the remodelling process, was also altered; in particular there was a notable reduction in inflammatory Ly6C+ monocytes at day 3 and an increase in anti-inflammatory CD206+ macrophages at day 7. Taken together, these results indicate that the IGF-1Ea transgene shifts the balance of innate immune cell populations early after infarction, favouring a reduction in inflammatory myeloid cells. This correlates with reduced extracellular matrix remodelling and changes in collagen composition that may confer enhanced scar elasticity and improved cardiac function.

  17. Role of Bradykinin on Left Ventricular Remodeling and Cardiac Function after Myocardial Infarction in Rats

    Institute of Scientific and Technical Information of China (English)

    Hai-zhu ZHANG; Li-quan LEI; Chang-cong CUI; Jian LIU

    2009-01-01

    Objectives To investigate the influences of bradykinin (BK) on hemodynamics, left ventricular hypertrophy and interstitial collagen metabolism after myocardial infarction (MI) in rats and the contribution of BK in angiotensin-con-verting enzyme (ACE) inhibition therapy. Methods By means of hemodynamic measurements, morphometric study of myocyte hypertrophy and SDS-PAGE technique ,the effects of enalapril pressure (500μg·kg-1·day-1) ,enalapril(500μg·kg-1·day-1) with BK B2 receptor antagonist Hoe-140 (500μg·kg-1·day-1),angiotensin Ⅱ (AgII) type 1 (AT1) receptor antagonist losartan(3mg·kg-1·day-1)on mean arterial pressure (MAP) ,left ventricular end-dias-tolic pressure (LVEDP), as well as maximum positive left ventricular pressure change (+ dp/dtmax), Ⅴ(m) n, col-lagen content and the ratio of type Ⅰ to type Ⅲ collagen (Ⅰ / Ⅲ) of noninfarcted area were observed in rats after MI. Treatments were started on the 3rd day after MI and continued for another 28 days. Results Enalapril reduced LV-EDP, Ⅴ(m) n and collagen content as well as collagen Ⅰ/Ⅲ compared with the untreated MI group (P < 0. 05), and all of these effects of enalapril were partly blunted by concomitant treatment with hoe-140 (P < 0. 05). Losartan was less effective than enalapril (P < 0. 05). However, three treatment groups had no significant differences in + dp/dtmax and had similar reductions in MAP compared with untreated MI group. Conclusions BK can improve cardiac function and prevent left ventricular hypertrophy with myocardial fibrosis independent of blood pressure. The mechanisms of ACEI are both blockade of Ang Ⅱ formation and inhibition of BK degradation.

  18. Adaptations to iron deficiency: cardiac functional responsiveness to norepinephrine, arterial remodeling, and the effect of beta-blockade on cardiac hypertrophy

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    Walker LeeAnn

    2002-01-01

    Full Text Available Abstract Background Iron deficiency (ID results in ventricular hypertrophy, believed to involve sympathetic stimulation. We hypothesized that with ID 1 intravenous norepinephrine would alter heart rate (HR and contractility, 2 abdominal aorta would be larger and more distensible, and 3 the beta-blocker propanolol would reduce hypertrophy. Methods 1 30 CD rats were fed an ID or replete diet for 1 week or 1 month. Norepinephrine was infused via jugular vein; pressure was monitored at carotid artery. Saline infusions were used as a control. The pressure trace was analyzed for HR, contractility, systolic and diastolic pressures. 2 Abdominal aorta catheters inflated the aorta, while digital microscopic images were recorded at stepwise pressures to measure arterial diameter and distensibility. 3 An additional 10 rats (5 ID, 5 control were given a daily injection of propanolol or saline. After 1 month, the hearts were excised and weighed. Results Enhanced contractility, but not HR, was associated with ID hypertrophic hearts. Systolic and diastolic blood pressures were consistent with an increase in arterial diameter associated with ID. Aortic diameter at 100 mmHg and distensibility were increased with ID. Propanolol was associated with an increase in heart to body mass ratio. Conclusions ID cardiac hypertrophy results in an increased inotropic, but not chronotropic response to the sympathetic neurotransmitter, norepinephrine. Increased aortic diameter is consistent with a flow-dependent vascular remodeling; increased distensibility may reflect decreased vascular collagen content. The failure of propanolol to prevent hypertrophy suggests that ID hypertrophy is not mediated via beta-adrenergic neurotransmission.

  19. A Transgenic Platform for Testing Drugs Intended for Reversal of Cardiac Remodeling Identifies a Novel 11βHSD1 Inhibitor Rescuing Hypertrophy Independently of Re-Vascularization

    OpenAIRE

    Oren Gordon; Zhiheng He; Dan Gilon; Sabine Gruener; Sherrie Pietranico-Cole; Amit Oppenheim; Eli Keshet

    2014-01-01

    RATIONALE: Rescuing adverse myocardial remodeling is an unmet clinical goal and, correspondingly, pharmacological means for its intended reversal are urgently needed. OBJECTIVES: To harness a newly-developed experimental model recapitulating progressive heart failure development for the discovery of new drugs capable of reversing adverse remodeling. METHODS AND RESULTS: A VEGF-based conditional transgenic system was employed in which an induced perfusion deficit and a resultant compromised ca...

  20. Renal denervation mitigates cardiac remodeling and renal damage in Dahl rats: a comparison with β-receptor blockade.

    Science.gov (United States)

    Watanabe, Heitaro; Iwanaga, Yoshitaka; Miyaji, Yuki; Yamamoto, Hiromi; Miyazaki, Shunichi

    2016-04-01

    Chronic activation of the sympathetic nervous system (SNS) contributes to cardiac remodeling and the transition to heart failure (HF). Renal sympathetic denervation (RDN) may ameliorate this damage by improving renal function and sympathetic cardioregulation in hypertensive HF patients with renal injury. The efficacy may be comparable to that of chronic β-blocker treatment. Dahl salt-sensitive hypertensive rats were subjected to RDN in the hypertrophic stage. Another group of Dahl rats were subjected to sham operations and treated chronically with vehicle (CONT) or β-blocker bisoprolol (BISO). Neither RDN nor BISO altered the blood pressure; however, BISO significantly reduced the heart rate (HR). Both RDN and BISO significantly prolonged survival (22.2 and 22.4 weeks, respectively) compared with CONT (18.3 weeks). Echocardiography revealed reduced left ventricular (LV) hypertrophy and improved LV function, and histological analysis demonstrated the amelioration of LV myocyte hypertrophy and fibrosis in the RDN and BISO rats at the HF stage. Tyrosine hydroxylase and β1-adrenergic receptor (ADR) expression levels in the LV myocardium significantly increased only in the RDN rats, whereas the α1b-, α1d- and α2c-ADR expression levels increased only in the BISO rats. In both groups, renal damage and dysfunction were also reduced, and this reduction was accompanied by the suppression of endothelin-1, renin and angiotensin-converting enzyme mRNAs. RDN ameliorated the progression of both myocardial and renal damage in the hypertensive rats independent of blood pressure changes. The overall effects were similar to those of β-receptor blockade with favorable effects on HR and α-ADR expression. These findings may be associated with the restoration of the myocardial SNS and renal protection. PMID:26631854

  1. The Combined Effect of Endurance Training and Various Doses of Atorvastatin on Cardiac Remodeling after Myocardial Infarction in Male Rats

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    Hadi Abdi

    2015-12-01

    Full Text Available Introduction: Statins and exercise have beneficial effects in preventing cardiovascular diseases. However, prolonged use of statins particularly at high doses has unpleasant side effects. This study aimed to investigate the combined effect of endurance training and three doses of Atorvastatin on cardiac remodeling after myocardial infarction in male rats.Methods: 75 male wistar rats (weighing 210-250g were randomly divided to 9 groups. Sham, control, endurance training, Atorvastatin (5, 10 and 15 mg/kg, and exercise plus Atorvastatin (5, 10 and 15 mg/kg: Myocardial infarction was induced by subcutaneous injection of isoprenaline (150 mg/kg in two consecutive days. Drug and training intervention was initiated 2 days after infarction and continued for 4 weeks. In order to assess the necrosis lesion and fibrosis tissue, hematoxylin & eosin and masson trichrome staining were used respectively.Results: The combination of endurance training and various doses of Atorvastatin significantly reduced the amount of necrosis and fibrosis tissue compared with the control group (P<0.01. Endurance exercise training alone did not cause significant changes in the extent of necrosis damage, but significantly increased fibrosis tissue compared with the control group (P<0.001. Various doses of Atorvastatin alone significantly reduced necrosis damage (P<0.001, but the difference between these groups and the control group in terms of fibrous tissue was statistically significant only at dose of 15 mg/kg (P<0.001.Conclusion: The results of this study showed that the combination of training and various doses of Atorvastatin are more effective in improving of tissue damage caused by myocardial infarction than exercise and Atorvastatin alone. However, the use of endurance training with medical therapy can not reduce the dose of Atorvastatin.

  2. Serum MMP-8: A Novel Indicator of Left Ventricular Remodeling and Cardiac Outcome in Patients after Acute Myocardial Infarction

    OpenAIRE

    Marie Fertin; Gilles Lemesle; Annie Turkieh; Olivia Beseme; Maggy Chwastyniak; Philippe Amouyel; Christophe Bauters; Florence Pinet

    2013-01-01

    OBJECTIVE: Left ventricular (LV) remodeling following myocardial infarction (MI) is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are an integral part of left ventricular (LV) rem...

  3. Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc

    OpenAIRE

    Heineke, Joerg; Ruetten, Hartmut; Willenbockel, Christian; Gross, Sandra C.; Naguib, Marian; Schaefer, Arnd; Kempf, Tibor; Hilfiker-Kleiner, Denise; Caroni, Pico; Kraft, Theresia; Kaiser, Robert A.; Molkentin, Jeffery D; Drexler, Helmut; Wollert, Kai C.

    2005-01-01

    Adverse left ventricular (LV) remodeling after myocardial infarction (MI) is a major cause for heart failure. Molecular modifiers of the remodeling process remain poorly defined. Patients with heart failure after MI have reduced LV expression levels of muscle LIM protein (MLP), a component of the sarcomeric Z-disk that is involved in the integration of stress signals in cardiomyocytes. By using heterozygous MLP mutant (MLP+/—) mice, we explored the role of MLP in post-MI remodeling. LV dimens...

  4. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling

    Science.gov (United States)

    Dietrich, Johannes W.; Müller, Patrick; Schiedat, Fabian; Schlömicher, Markus; Strauch, Justus; Chatzitomaris, Apostolos; Klein, Harald H.; Mügge, Andreas; Köhrle, Josef; Rijntjes, Eddy; Lehmphul, Ina

    2015-01-01

    Background Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. Methods Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. Results Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. Conclusion This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms. PMID:26279999

  5. Mechanobiological regulation of bone remodeling -- Theoretical development of a coupled systems biology-micromechanical approach

    OpenAIRE

    Scheiner, Stefan; Pivonka, Peter; Hellmich, Christian; Smith, David W.

    2012-01-01

    Bone remodeling involves the coordinated removal of bone by osteoclasts and addition of bone by osteoblasts, a process that is modulated by the prevailing mechanical environment. In this paper a fully coupled model of bone remodeling is developed, based on coupling a bone cell population model with a micromechanical homogenization scheme of bone stiffness. While the former model considers biochemical regulatory mechanisms between bone cells such as the RANK-RANKL-OPG pathway and action of TGF...

  6. Effects of Long-term Ramipril on Ventricular Remodeling, Cardiac Function and Survival in Rat Congestive Heart Failure after Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    陶则伟; 黄元伟

    2004-01-01

    Objectives The purpose of this study was to investigate the effects of long-term ramipril on ventricular remodeling, cardiac function and survival in rat congestive heart failure after myocardial infarction. Methods Myocardial infarction (MI) was caused by ligation of the left anterior descending coronary artery in rats. 7 days after the surgery, the surviving rats were randomly assigned to the following treatment protocols: 1) MI rats with no therapy, 2) MI rats treated with ramipril 3 mg/kg per day, 3) Sham-operated control rats, and 4) Sham-operated rats treated with ramipril 3 mg/kg per day. At 22 weeks, cardiac hemodynamic parameters such as MAP, LVSP, ±dP/dtmax and LVEDP were measured,and cardiac morphometric parameters such as HW,LVW and LVCA were measured, mRNA of cardiacmolecule genes, such as βMHC, BNP, collagen Ⅰ and Ⅲ, and TGF-β1, were quantified, and survival rates were calculated. Results Compared with sham-operated rats, MI rats without therapy showed significant increases in cardiac morphological parameters as well as in mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and survival rate shortened (P<0.05). Compared with MI rats with no therapy, MI rats treated with ramipril showed significant attenuation of mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly impaired (P<0.01), and survival rate shortened (P<0.05). Compared with MI rats with no therapy, MI rats treated with ramipril showed significant attenuation of mRAN expressions of cardiac molecule genes (P<0.01); while their hemodynamic parameters were significantly improved (P<0.05 or P<0.01), and survival rates prolonged (P<0.05). Conclusions Treatment with long-term ramipril may improve LV remodeling, cardiac function and survival in rat congestive heart failure after MI.

  7. High Intensity Interval and Endurance Training Have Opposing Effects on Markers of Heart Failure and Cardiac Remodeling in Hypertensive Rats

    Science.gov (United States)

    Holloway, Tanya M.; Bloemberg, Darin; da Silva, Mayne L.; Simpson, Jeremy A.; Quadrilatero, Joe; Spriet, Lawrence L.

    2015-01-01

    There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characteristics involved in the development of diastolic dysfunction, such as ventricular hypertrophy, fibrosis and angiogenesis, in a well-established rodent model of hypertension-induced heart failure before the development of overt heart failure. ET decreased left ventricle fibrosis by ~40% (P HIIT did not decrease existing fibrosis, and HIIT animals displayed a 20% increase in left ventricular mass (PHIIT also increased brain natriuretic peptide by 50% (PHIIT promoted a pathological adaptation in the left ventricle in the presence of hypertension, highlighting the need for further research on the widespread effects of HIIT in the presence of disease. PMID:25803693

  8. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast): a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

    International Nuclear Information System (INIS)

    MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research) is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker) can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer. One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril), beta-blocker (bisoprolol), or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1) determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2) understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3) correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer. Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first randomized trial testing proven heart failure pharmacotherapy in

  9. Rationale and design of the Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research Trial (MANTICORE 101 - Breast: a randomized, placebo-controlled trial to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer using cardiac MRI

    Directory of Open Access Journals (Sweden)

    Ezekowitz Justin

    2011-07-01

    Full Text Available Abstract Background MANTICORE 101 - Breast (Multidisciplinary Approach to Novel Therapies in Cardiology Oncology Research is a randomized trial to determine if conventional heart failure pharmacotherapy (angiotensin converting enzyme inhibitor or beta-blocker can prevent trastuzumab-mediated left ventricular remodeling, measured with cardiac MRI, among patients with HER2+ early breast cancer. Methods/Design One hundred and fifty-nine patients with histologically confirmed HER2+ breast cancer will be enrolled in a parallel 3-arm, randomized, placebo controlled, double-blind design. After baseline assessments, participants will be randomized in a 1:1:1 ratio to an angiotensin-converting enzyme inhibitor (perindopril, beta-blocker (bisoprolol, or placebo. Participants will receive drug or placebo for 1 year beginning 7 days before trastuzumab therapy. Dosages for all groups will be systematically up-titrated, as tolerated, at 1 week intervals for a total of 3 weeks. The primary objective of this randomized clinical trial is to determine if conventional heart failure pharmacotherapy can prevent trastuzumab-mediated left ventricular remodeling among patients with HER2+ early breast cancer, as measured by 12 month change in left ventricular end-diastolic volume using cardiac MRI. Secondary objectives include 1 determine the evolution of left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer, 2 understand the mechanism of trastuzumab mediated cardiac toxicity by assessing for the presence of myocardial injury and apoptosis on serum biomarkers and cardiac MRI, and 3 correlate cardiac biomarkers of myocyte injury and extra-cellular matrix remodeling with left ventricular remodeling on cardiac MRI in patients with HER2+ early breast cancer. Discussion Cardiac toxicity as a result of cancer therapies is now recognized as a significant health problem of increasing prevalence. To our knowledge, MANTICORE will be the first

  10. Pediatric cardiac surgery in developing countries.

    Science.gov (United States)

    Rao, Suresh G

    2007-01-01

    Pediatric cardiac surgery in developing countries is a major challenge. It is a challenge to employ evolving methods to cater to the surgical needs of a very large number of children with congenital heart defects while dealing with severe budgetary constraints, finding funding to maintain the program, and maintaining quality in the backdrop of constant turnover of trained medical, nursing, and other paramedical personnel. Choosing the best procedure to achieve maximum palliation at lower cost and, when possible, giving priority for one-stage corrective procedures, albeit at a higher risk, calls for practice modifications. Despite improved infrastructure and surgical skills in recent years, in some developing countries, logistics, affordability, late presentation, nutritional issues, staffing, and unfavorable economics continue to negatively influence the overall results compared to those of developed nations. PMID:17486389

  11. Hypertension is a conditional factor for the development of cardiac hypertrophy in type 2 diabetic mice.

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    Marc van Bilsen

    Full Text Available BACKGROUND: Type 2 diabetes is frequently associated with co-morbidities, including hypertension. Here we investigated if hypertension is a critical factor in myocardial remodeling and the development of cardiac dysfunction in type 2 diabetic db/db mice. METHODS: Thereto, 14-wks-old male db/db mice and non-diabetic db/+ mice received vehicle or angiotensin II (AngII for 4 wks to induce mild hypertension (n = 9-10 per group. Left ventricular (LV function was assessed by serial echocardiography and during a dobutamine stress test. LV tissue was subjected to molecular and (immunohistochemical analysis to assess effects on hypertrophy, fibrosis and inflammation. RESULTS: Vehicle-treated diabetic mice neither displayed marked myocardial structural remodeling nor cardiac dysfunction. AngII-treatment did not affect body weight and fasting glucose levels, and induced a comparable increase in blood pressure in diabetic and control mice. Nonetheless, AngII-induced LV hypertrophy was significantly more pronounced in diabetic than in control mice as assessed by LV mass (increase +51% and +34%, respectively, p<0.01 and cardiomyocyte size (+53% and +31%, p<0.001. This was associated with enhanced LV mRNA expression of markers of hypertrophy and fibrosis and reduced activation of AMP-activated protein kinase (AMPK, while accumulation of Advanced Glycation End products (AGEs and the expression levels of markers of inflammation were not altered. Moreover, AngII-treatment reduced LV fractional shortening and contractility in diabetic mice, but not in control mice. CONCLUSIONS: Collectively, the present findings indicate that type 2 diabetes in its early stage is not yet associated with adverse cardiac structural changes, but already renders the heart more susceptible to hypertension-induced hypertrophic remodeling.

  12. Left Right Patterning, Evolution and Cardiac Development

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    Iain M. Dykes

    2014-04-01

    Full Text Available Many aspects of heart development are determined by the left right axis and as a result several congenital diseases have their origins in aberrant left-right patterning. Establishment of this axis occurs early in embryogenesis before formation of the linear heart tube yet impacts upon much later morphogenetic events. In this review I discuss the differing mechanisms by which left-right polarity is achieved in the mouse and chick embryos and comment on the evolution of this system. I then discus three major classes of cardiovascular defect associated with aberrant left-right patterning seen in mouse mutants and human disease. I describe phenotypes associated with the determination of atrial identity and venous connections, looping morphogenesis of the heart tube and finally the asymmetric remodelling of the embryonic branchial arch arterial system to form the leftward looped arch of aorta and associated great arteries. Where appropriate, I consider left right patterning defects from an evolutionary perspective, demonstrating how developmental processes have been modified in species over time and illustrating how comparative embryology can aide in our understanding of congenital heart disease.

  13. Serum MMP-8: a novel indicator of left ventricular remodeling and cardiac outcome in patients after acute myocardial infarction.

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    Marie Fertin

    Full Text Available OBJECTIVE: Left ventricular (LV remodeling following myocardial infarction (MI is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs and tissue inhibitors of metalloproteinases (TIMPs, are an integral part of left ventricular (LV remodeling after myocardial infarction (MI. We investigated the temporal profile of circulating MMPs and TIMPs and their relations with LV remodeling at 1 year and clinical outcome at 3 years in post-MI patients. METHODS: This prospective multicentre study included 246 patients with a first anterior MI. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI, and analysed at a core laboratory. LV remodeling was defined as the percent change in LV end-diastolic volume (EDV from baseline to 1 year. Serum samples were obtained at hospital discharge, 1, 3, and 12 months. Multiplex technology was used for analysis of MMP-1, -2, -3, -8, -9, -13, and TIMP-1, -2, -3, -4 serum levels. RESULTS: Baseline levels of MMP-8 and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02, respectively. When adjusted for major baseline characteristics, MMP-8 levels remained an independent predictor LV remodeling (P = 0.025. By univariate analysis, there were positive relations between cardiovascular death or hospitalization for heart failure during the 3-year follow-up and the baseline levels of MMP-2 (P = 0.03, MMP-8 (P = 0.002, and MMP-9 (P = 0.03. By multivariate analysis, MMP-8 was the only MMP remaining significantly associated with clinical outcome (P = 0.02. CONCLUSION: Baseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve

  14. Comparative Characterization of Cardiac Development Specific microRNAs: Fetal Regulators for Future.

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    Yashika Rustagi

    Full Text Available MicroRNAs (miRNAs are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. However, there is no study which elucidates the profiling of miRNAs during development of heart till date. Very limited miRNAs have been reported to date in cardiac context. In addition, integration of large scale experimental data with computational and comparative approaches remains an unsolved challenge.The present study was designed to identify the microRNAs implicated in heart development using next generation sequencing, bioinformatics and experimental approaches. We sequenced six small RNA libraries prepared from different developmental stages of the heart using chicken as a model system to produce millions of short sequence reads. We detected 353 known and 703 novel miRNAs involved in heart development. Out of total 1056 microRNAs identified, 32.7% of total dataset of known microRNAs displayed differential expression whereas seven well studied microRNAs namely let-7, miR-140, miR-181, miR-30, miR-205, miR-103 and miR-22 were found to be conserved throughout the heart development. The 3'UTR sequences of genes were screened from Gallus gallus genome for potential microRNA targets. The target mRNAs were appeared to be enriched with genes related to cell cycle, apoptosis, signaling pathways, extracellular remodeling, metabolism, chromatin remodeling and transcriptional regulators. Our study presents the first comprehensive overview of microRNA profiling during heart development and prediction of possible cardiac specific targets and has a big potential in future to develop microRNA based therapeutics against cardiac pathologies where fetal gene re-expression is witnessed in adult heart.

  15. Gene Regulatory Networks in Cardiac Conduction System Development

    OpenAIRE

    Munshi, Nikhil V.

    2012-01-01

    The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Given its critical role in coordinating cardiac performance, a detailed analysis of the molecular mechanisms underlying conduction system formation should inform our understanding of arrhythmia pathophysiology and affect the development of novel therapeutic strategies. Historically, the ability to distinguish cells of the conduction system from neighboring working myocyt...

  16. Model digital signal cardiac processing in developed Matlab

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    Kervin Benito Rojas Ochoa

    2013-09-01

    Full Text Available ABSTRACTThe present research aimed to design a model of digital cardiac signal processing developed in MatLab. This is because they wanted to use the potentialities of the computer tool, to emulate a digital processing environment. The design is not experimental, transactional since this model does not directly manipulates the cardiac patient information, but uses the theoretical characteristics of the variable in study. In addition, research is documentary, driven by the precepts of a feasible project, whose methodology consisted of four key stages: characterization of cardiac signal, establishment of the requirements for filtering of cardiac wave, sampling and coding of the signal, and representation of the model in MatLab, as a result, achieved the model of digital processing of cardiac signals using the MatLab tool and corroborating their applicability.Keywords: Model, Process, Cardiac Signals, MatLab.

  17. High Intensity Interval and Endurance Training Have Opposing Effects on Markers of Heart Failure and Cardiac Remodeling in Hypertensive Rats

    OpenAIRE

    Holloway, Tanya M.; Bloemberg, Darin; da Silva, Mayne L.; Simpson, Jeremy A.; Quadrilatero, Joe; Spriet, Lawrence L.

    2015-01-01

    There has been re-emerging interest and significant work dedicated to investigating the metabolic effects of high intensity interval training (HIIT) in recent years. HIIT is considered to be a time efficient alternative to classic endurance training (ET) that elicits similar metabolic responses in skeletal muscle. However, there is a lack of information on the impact of HIIT on cardiac muscle in disease. Therefore, we determined the efficacy of ET and HIIT to alter cardiac muscle characterist...

  18. Combined score using clinical, electrocardiographic, and echocardiographic parameters to predict left ventricular remodeling in patients having had cardiac resynchronization therapy six months earlier.

    Science.gov (United States)

    Brunet-Bernard, Anne; Maréchaux, Sylvestre; Fauchier, Laurent; Guiot, Aurélie; Fournet, Maxime; Reynaud, Amélie; Schnell, Frédéric; Leclercq, Christophe; Mabo, Philippe; Donal, Erwan

    2014-06-15

    The aim of this study was to evaluate whether a scoring system integrating clinical, electrocardiographic, and echocardiographic measurements can predict left ventricular reverse remodeling after cardiac resynchronization therapy (CRT). The derivation cohort consisted of 162 patients with heart failure implanted with a CRT device. Baseline clinical, electrocardiographic, and echocardiographic characteristics were entered into univariate and multivariate models to predict reverse remodeling as defined by a ≥15% reduction in left ventricular end-systolic volume at 6 months (60%). Combinations of predictors were then tested under different scoring systems. A new 7-point CRT response score termed L2ANDS2: Left bundle branch block (2 points), Age >70 years, Nonischemic origin, left ventricular end-diastolic Diameter 5 had a high positive likelihood ratio (+LR = 5.64), whereas a score <2 had a high negative likelihood ratio (-LR = 0.19). In conclusion, this L2ANDS2 score provides an easy-to-use tool for the clinician to assess the pretest probability of a patient being a CRT responder. PMID:24793667

  19. βA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development

    Science.gov (United States)

    Sinha, Debasish; Klise, Andrew; Sergeev, Yuri; Hose, Stacey; Bhutto, Imran A.; Hackler, Laszlo; Malpic-llanos, Tanya; Samtani, Sonia; Grebe, Rhonda; Goldberg, Morton F.; Hejtmancik, J. Fielding; Nath, Avindra; Zack, Donald J.; Fariss, Robert N.; McLeod, D. Scott; Sundin, Olof; Broman, Karl W.; Lutty, Gerard A.; Zigler, J. Samuel

    2016-01-01

    Vascular remodeling is a complex process critical to development of the mature vascular system. Astrocytes are known to be indispensable for initial formation of the retinal vasculature; our studies with the Nuc1 rat provide novel evidence that these cells are also essential in the retinal vascular remodeling process. Nuc1 is a spontaneous mutation in the Sprague–Dawley rat originally characterized by nuclear cataracts in the heterozygote and microphthalmia in the homozygote. We report here that the Nuc1 allele results from mutation of the βA3/A1-crystallin gene, which in the neural retina is expressed only in astrocytes. We demonstrate striking structural abnormalities in Nuc1 astrocytes with profound effects on the organization of intermediate filaments. While vessels form in the Nuc1 retina, the subsequent remodeling process required to provide a mature vascular network is deficient. Our data implicate βA3/A1-crystallin as an important regulatory factor mediating vascular patterning and remodeling in the retina. PMID:17931883

  20. Roles of FGFs as adipokines in adipose tissue development, remodeling, and metabolism

    OpenAIRE

    NobuyukiItoh

    2014-01-01

    White and brown adipose tissues, which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among twenty-two FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and brown adipose tissues. FGF1 is a critical transducer in white adipose tissue remodeling. The PPARγ–F...

  1. Development and evaluation of cardiac motion simulation phantom for MDCT

    International Nuclear Information System (INIS)

    The clinical usefulness of MDCT (multidetector-row-CT) is determined by its ability to obtain thinner slices through a wider portion of the body. Thus, MDCT provides improvement of time resolution and high quality reconstruction images. In particular, clinical application for the heart and coronary arteries is difficult by CT, excluding EBCT (electron beam CT), because of its poor time resolution. However, MDCT has improved the time resolution of CT and is used for cardiac and coronary disease evaluation. Reports regarding delineation of cardiac diseases with MDCT have recently increased and many successful cases have been reported. We developed a cardiac phantom for electrocardiograms (ECG) gated MDCT to better understand the function of MDCT. The phantom closely simulates motion of the left ventricle while providing a valuable tool to evaluate coronary stenosis and calcification making this newly developed cardiac phantom for ECG gated MDCT useful for functional evaluation of cardiac MDCT. (author)

  2. Proliferative responses to myocardial remodeling in the developing heart

    Czech Academy of Sciences Publication Activity Database

    Sedmera, David; Kučera, P.; Kolář, František; Thompson, R.P.

    1. Malden: Blackwell Publishing, 2005 - (Artman, M.; Benson, W.; Srivastava, D.; Nakazawa, M.), s. 47-51 ISBN 1-4051-3128-4 R&D Projects: GA MŠk(CZ) 1M0510 Grant ostatní: NIH(US) HL50582; SC COBRE in Cardiovascular Diseases(US) RR 16434-01; MOD Basil O'Connor(US) 5-FY03-118 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiomyocyte * hyperplasia * development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  3. Development of a postgraduate interventional cardiac nursing curriculum.

    Science.gov (United States)

    Currey, Judy; White, Kevin; Rolley, John; Oldland, Elizabeth; Driscoll, Andrea

    2015-11-01

    Interventional cardiology practices have advanced immensely in the last two decades, but the educational preparation of the workforce in cardiac catheter laboratories has not seen commensurate changes. Although on-the-job training has sufficed in the past, recognition of this workforce as a specialty practice domain now demands specialist educational preparation. The aim of this paper is to present the development of an interventional cardiac nursing curriculum nested within a Master of Nursing Practice in Australia. International and national health educational principles, teaching and learning theories and professional frameworks and philosophies are foundational to the program designed for interventional cardiac specialist nurses. These broader health, educational and professional underpinnings will be described to illustrate their application to the program's theoretical and clinical components. Situating interventional cardiac nursing within a Master's degree program at University provides nurses with the opportunities to develop high level critical thinking and problem solving knowledge and skills. PMID:25687694

  4. Sudden cardiac death in dogs with remodeled hearts is associated with larger beat-to-beat variability of repolarization

    DEFF Research Database (Denmark)

    Thomsen, Morten Bækgaard; Truin, Michiel; van Opstal, Jurren M;

    2005-01-01

    diminished reserve and larger propensity for repolarization-dependent ventricular arrhythmia. A subset of chronic AVB dogs (10%) suffers sudden cardiac death (SCD). With the assumption that repolarization defects constitute a potentially lethal proarrhythmic substrate, we hypothesized that BVR in SCD dogs...... group. All other electrophysiological parameters (RR, QT and MAP durations) were comparable for the two groups. Extending the number of animals and groups confirmed a larger BVR in the SCD group (SCD: 5.1 +/- 2.7; n = 11 versus control: 2.5 +/- 0.4 ms; n = 61; P <0.05) and showed reverse-use dependence...

  5. Improvement of cardiac function and reversal of gap junction remodeling by Neuregulin-1β in volume-overloaded rats with heart failure

    Institute of Scientific and Technical Information of China (English)

    Xue-Hui Wang; Xiao-Zhen Zhuo; Ya-Juan Ni; Min Gong; Ting-Zhong Wang; Qun Lu; Ai-Qun Ma

    2012-01-01

    Objective We performed experiments using Neuregulin-1β (NRG-1β) treatment to determine a mechanism for the protective role derived from its beneficial effects by remodeling gap junctions (GJs) during heart failure (HF). Methods Rat models of HF were established by aortocaval fistula. Forty-eight rats were divided randomly into the HF (HF, n = 16), NRG-1β treatment (NRG, n = 16), and sham operation (S, n = 16) group. The rats in the NRG group were administered NRG-1β (10 μg/kg per day) for 7 days via the tail vein, whereas the other groups were injected with the same doses of saline. Twelve weeks after operation, Connexin 43 (Cx43) expression in single myocytes obtained from the left ventricle was determined by immunocytochemistry. Total protein was extracted from frozen left ventricular tissues for immunoblotting assay, and the ultrastructure of myocytes was observed by transmission electron microscopy. Results Compared with the HF group, the cardiac function of rats in the NRG group was markedly improved, irregular distribution and deceased Cx43 expression were relieved. The ultrastructure of myocytes was seriously damaged in HF rats, and NRG-1β reduced these pathological damages. Conclusions Short-term NRG-1β treatment can rescue pump failure in experimental models of volume overload-induced HF, which is related to the recovery of GJs structure and the improvement of Cx43 expression.

  6. Diverse functions of ATP-dependent chromatin remodeling complexes in development and cancer

    Institute of Scientific and Technical Information of China (English)

    Jiang I. Wu

    2012-01-01

    Mammalian SWI/SNF like Brg1/Brm associated factors (BAF) chromatin-remodeling complexes are able to use energy derived from adenosine triphosphate (ATP) hydrolysis to change chromatin structures and regulate nuclear processes such as transcription.BAF complexes contain multiple subunits and the diverse subunit compositions provide functional specificities to BAF complexes.In this review,we summarize the functions of BAF subunits during mammalian development and in progression of various cancers.The mechanisms underlying the functional diversity and specificities of BAF complexes will be discussed.

  7. Assessment of cardiac remodeling in asymptomatic mitral regurgitation for surgery timing: a comparative study of echocardiography and magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Ozdogan Oner

    2010-08-01

    Full Text Available Abstract Background Early surgery is recommended for asymptomatic severe mitral regurgitation (MR, because of increased postoperative left ventricular (LV dysfunction in patients with late surgery. On the other hand, recent reports emphasized a "watchful waiting" process for the determination of the proper time of mitral valve surgery. In our study, we compared magnetic resonance imaging (MRI and transthoracic echocardiography to evaluate the LV and left atrial (LA remodeling; for better definitions of patients that may benefit from early valve surgery. Methods Twenty-one patients with moderate to severe asymptomatic MR were evaluated by echocardiography and MRI. LA and LV ejection fractions (EFs were calculated by echocardiography and MRI. Pulmonary veins (PVs were measured from vein orifices in diastole and systole from the tangential of an imaginary circle that completed LA wall. Right upper PV indices were calculated with the formula; (Right upper PV diastolic diameter- Right upper PV systolic diameter/Right upper PV diastolic diameter. Results In 9 patients there were mismatches between echocardiography and MRI measurements of LV EF. LV EFs were calculated ≥60% by echocardiography, meanwhile 0.05. However, both right upper PV indices (0.16 ± 0.06 vs. 0.24 ± 0.08, p: 0.024 and LA EFs (0.19 ± 0.09 vs. 0.33 ± 0.14, p: 0.025 were significantly decreased in patients with depressed EFs when compared to patients with normal EFs. Conclusions MRI might be preferred when small changes in functional parameters like LV EF, LA EF, and PV index are of clinical importance to disease management like asymptomatic MR patients that we follow up for appropriate surgery timing.

  8. Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration

    Directory of Open Access Journals (Sweden)

    Kenneth R. Boheler

    2011-01-01

    Full Text Available Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.

  9. Potassium Channel Interacting Protein 2 (KChIP2) is not a transcriptional regulator of cardiac electrical remodeling.

    Science.gov (United States)

    Winther, Sine V; Tuomainen, Tomi; Borup, Rehannah; Tavi, Pasi; Antoons, Gudrun; Thomsen, Morten B

    2016-01-01

    The heart-failure relevant Potassium Channel Interacting Protein 2 (KChIP2) augments CaV1.2 and KV4.3. KChIP3 represses CaV1.2 transcription in cardiomyocytes via interaction with regulatory DNA elements. Hence, we tested nuclear presence of KChIP2 and if KChIP2 translocates into the nucleus in a Ca(2+) dependent manner. Cardiac biopsies from human heart-failure patients and healthy donor controls showed that nuclear KChIP2 abundance was significantly increased in heart failure; however, this was secondary to a large variation of total KChIP2 content. Administration of ouabain did not increase KChIP2 content in nuclear protein fractions in anesthetized mice. KChIP2 was expressed in cell lines, and Ca(2+) ionophores were applied in a concentration- and time-dependent manner. The cell lines had KChIP2-immunoreactive protein in the nucleus in the absence of treatments to modulate intracellular Ca(2+) concentration. Neither increasing nor decreasing intracellular Ca(2+) concentrations caused translocation of KChIP2. Microarray analysis did not identify relief of transcriptional repression in murine KChIP2(-/-) heart samples. We conclude that although there is a baseline presence of KChIP2 in the nucleus both in vivo and in vitro, KChIP2 does not directly regulate transcriptional activity. Moreover, the nuclear transport of KChIP2 is not dependent on Ca(2+). Thus, KChIP2 does not function as a conventional transcription factor in the heart. PMID:27349185

  10. Epigenetic regulation by BAF (mSWI/SNF) chromatin remodeling complexes is indispensable for embryonic development.

    Science.gov (United States)

    Nguyen, Huong; Sokpor, Godwin; Pham, Linh; Rosenbusch, Joachim; Stoykova, Anastassia; Staiger, Jochen F; Tuoc, Tran

    2016-05-18

    The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex. The generated dcKO mutant provides a novel and powerful tool for investigating how entire BAF complexes affect cortical development. Using this model, we found that BAF complexes globally control the key heterochromatin marks, H3K27me2 and -3, by directly modulating the enzymatic activity of the H3K27 demethylases, Utx and Jmjd3. Here, we present further insights into how the scaffolding ability of the BAF155 and BAF170 core subunits maintains the stability of BAF complexes in the forebrain and throughout the embryo during development. Furthermore, we show that the loss of BAF complexes in the above-described model up-regulates H3K27me3 and impairs forebrain development and embryogenesis. These findings improve our understanding of epigenetic mechanisms and their modulation by the chromatin-remodeling SWI/SNF complexes that control embryonic development. PMID:26986003

  11. CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis.

    Directory of Open Access Journals (Sweden)

    Po-Yin Chu

    Full Text Available Heart failure (HF is an increasingly recognized complication of diabetes. Cardiac fibrosis is an important causative mechanism of HF associated with diabetes. Recent data indicate that inflammation may be particularly important in the pathogenesis of cardiovascular fibrosis. We sought to determine the mechanism by which cardiac fibrosis develops and to specifically investigate the role of the CXCR4 axis in this process. Animals with type I diabetes (streptozotocin treated mice or type II diabetes (Israeli Sand-rats and controls were randomized to treatment with a CXCR4 antagonist, candesartan or vehicle control. Additional groups of mice also underwent bone marrow transplantation (GFP+ donor marrow to investigate the potential role of bone marrow derived cell mobilization in the pathogenesis of cardiac fibrosis. Both type I and II models of diabetes were accompanied by the development of significant cardiac fibrosis. CXCR4 antagonism markedly reduced cardiac fibrosis in both models of diabetes, similar in magnitude to that seen with candesartan. In contrast to candesartan, the anti-fibrotic actions of CXCR4 antagonism occurred in a blood pressure independent manner. Whilst the induction of diabetes did not increase the overall myocardial burden of GFP+ cells, it was accompanied by an increase in GFP+ cells expressing the fibroblast marker alpha-smooth muscle actin and this was attenuated by CXCR4 antagonism. CXCR4 antagonism was also accompanied by increased levels of circulating regulatory T cells. Taken together the current data indicate that pharmacological inhibition of CXCR4 significantly reduces diabetes induced cardiac fibrosis, providing a potentially important therapeutic approach.

  12. Intrinsic Cardiac Autonomic Ganglionated Plexi within Epicardial Fats Modulate the Atrial Substrate Remodeling: Experiences with Atrial Fibrillation Patients Receiving Catheter Ablation

    Science.gov (United States)

    Singhal, Rahul; Lo, Li-Wei; Lin, Yenn-Jiang Lin; Chang, Shih-Lin; Hu, Yu-Feng; Chao, Tze-Fan; Chung, Fa-Po; Chiou, Cheun-Wang; Tsao, Hsuan-Ming; Chen, Shih-Ann

    2016-01-01

    Background A recent study reported the close relationship between high dominant frequent (DF) sites [atrial fibrillation (AF) nest] and the intrinsic cardiac autonomic nervous system. The aim of this study was to investigate the correlation between the regional distribution of epicardial fat and the properties of the biatrial substrates in AF patients. Methods We studied 32 patients with paroxysmal (n = 23) and persistent (n = 9) AF. The epicardial fat volume around the left atrium (LA) was evaluated using 64-slice multidetector computed tomography and the topographic distribution of the fat volume was assessed. The biatrial DFs, voltages, and total activation times (TATs) were obtained during sinus rhythm. Results Out of the 8 divided LA regions, a significant linear correlation existed between the LA fat and mean DF values in the right upper anterior LA, left upper anterior LA, right lower anterior LA, right upper posterior LA, left upper posterior LA, and left lower posterior LA. There was no significant correlation between the regional LA fat distribution and regional LA peak-to-peak bipolar voltage and TAT. During a mean follow-up of 17 ± 8 months, 22 of the 32 (69%) patients were free of AF. In the multivariate analysis, only the mean LA DF was found to be a significant predictor of recurrence. Conclusions There was a close association between the regional distribution of the LA epicardial fat and the atrial substrate manifesting high frequency during sinus rhythm (AF nest). Those nests were related to ablation outcome. Hence, epicardial fat may play a significant role in atrial substrate remodeling and thereby in the pathogenesis and maintenance of AF. PMID:27122948

  13. Identification of hub genes of cardiac remodeling by weighted gene co-expression network analysis%用权重基因共表达网络分析识别心脏重构关键节点基因

    Institute of Scientific and Technical Information of China (English)

    钟诗龙; 余细勇; 伍虹; 杨敏; 刘晓颖; 郑志伟; 林秋雄; 符永恒; 麦丽萍; 周志凌

    2011-01-01

    Cardiac remodeling after acute myocardial infarction is the main pathologic change of chronic heart failure. The balance of ACEI and ACE2 plays an important role in pathogenesis and treatment of chronic heart failure. However its upstream regulation mechanism is unclear. This study aimed to identify the hub genes of cardiac remodeling by mining publically available data sets using weighted gene co-expression network analysis ( WGCNA ) and to study their relationship with ACEI and ACE2 gene. Methods Two genome-wide expression data sets, GSE7487 and GSE738 . of cardiac remodeling after myocardial infarction were downloaded from NCBI GEO database.WGCNA was used to construct gene coexpression network. identify the modules and hub genes associated with cardiac remodeling. The correlation of expression of hub genes with ACEI and ACE2 was calculated and verified in an animal model of cardiac remodeling after myocardial infarction. Result Seventeen modules were found in GSE7487 and among which, 6 were significantlv correlated with cardiac remodeling and enriched in 16 KEGG pathways. Sixteen modules were found in GSE738 and among which, 5 were significantly correlated with cardiac remodeling and enriched in 15 KEGG pathways, 10 of which were the same as in the first dataset. Many signaling pathways involved pathological cardiac hypertrophy , oxidative phosphorylation ,and metabolism. A number of key regulatory genes of cardiac remodeling were further identified through module connectivity and gene significance. One of the key regulatory genes, calcium-dependent phosphatase regulon ( RCANI ). was found to be highly correlated with ACEI, but not ACE2. Their relationships were confirmed in an animal model. Conclusions Weighted gene co-expression network analysis is a robust systematic biological tool and can be used to identify the key regulatory genes of cardiac remodeling efficiently.RCANI may play an important role in regulating the balance of ACE1-ACE2 in renin

  14. MT1-MMP-mediated basement membrane remodeling modulates renal development

    Energy Technology Data Exchange (ETDEWEB)

    Riggins, Karen S.; Mernaugh, Glenda [Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Su, Yan; Quaranta, Vito [Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Koshikawa, Naohiko; Seiki, Motoharu [Division of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Pozzi, Ambra [Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Research Medicine, Veterans Affairs Hospital, Nashville, TN 37232 (United States); Zent, Roy, E-mail: roy.zent@vanderbilt.edu [Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Department of Research Medicine, Veterans Affairs Hospital, Nashville, TN 37232 (United States)

    2010-10-15

    Extracellular matrix (ECM) remodeling regulates multiple cellular functions required for normal development and tissue repair. Matrix metalloproteinases (MMPs) are key mediators of this process and membrane targeted MMPs (MT-MMPs) in particular have been shown to be important in normal development of specific organs. In this study we investigated the role of MT1-MMP in kidney development. We demonstrate that loss of MT1-MMP leads to a renal phenotype characterized by a moderate decrease in ureteric bud branching morphogenesis and a severe proliferation defect. The kidneys of MT1-MMP-null mice have increased deposition of collagen IV, laminins, perlecan, and nidogen and the phenotype is independent of the MT-1MMP target, MMP-2. Utilizing in vitro systems we demonstrated that MTI-MMP proteolytic activity is required for renal tubule cells to proliferate in three dimensional matrices and to migrate on collagen IV and laminins. Together these data suggest an important role for MT1-MMP in kidney development, which is mediated by its ability to regulate cell proliferation and migration by proteolytically cleaving kidney basement membrane components.

  15. Endothelial-Cardiomyocyte Interactions in Cardiac Development and Repair

    Science.gov (United States)

    Hsieh, Patrick C.H.; Davis, Michael E.; Lisowski, Laura K.; Lee, Richard T.

    2009-01-01

    Communication between endothelial cells and cardiomyocytes regulates not only early cardiac development but also adult cardiomyocyte function, including the contractile state. In the normal mammalian myocardium, each cardiomyocyte is surrounded by an intricate network of capillaries and is next to endothelial cells. Cardiomyocytes depend on endothelial cells not only for oxygenated blood supply but also for local protective signals that promote cardiomyocyte organization and survival. While endothelial cells direct cardiomyocytes, cardiomyocytes reciprocally secrete factors that impact endothelial cell function. Understanding how endothelial cells communicate with cardiomyocytes will be critical for cardiac regeneration, in which the ultimate goal is not simply to improve systolic function transiently but to establish new myocardium that is both structurally and functionally normal in the long term. PMID:16460266

  16. Molecular mechanism of carvedilol in attenuating the reversion to fetal energy metabolism during cardiac hypertrophy development

    Institute of Scientific and Technical Information of China (English)

    胡琴; 李隆贵

    2003-01-01

    Objective: To explore the molecular regulation mechanism of carvedilol in attenuating the reversion back towards fetal energy metabolism during the development of cardiac hypertrophy induced by coarctation of abdominal aorta (CAA) in male Wistar rats. Methods: Hemodynamic and ventricular remodeling parameters, free fatty acid content in the serum were measured in the experimental animals at 16 weeks after the surgical CAA, the rats receiving carvedilol intervention (CAR) after CAA, and those with sham operation (SH). The expressions of muscle carnitine palmitoyltransferaseⅠ (M-CPTⅠ) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the cardiac myocytes from every group were studied with RT-PCR. Results: Significant left ventricular hypertrophy were observed in the rats 16 weeks after coarctation operation (P<0.05), together with significant free fatty acids accumulation and downregulation of M-CPTⅠ and MCAD mRNA (P<0.05) in CAA group. Carvedilol at a dose of 30 mg/kg/d for 12 weeks inhibited the left ventricular hypertrophy induced by pressure overload and enhanced the gene expressions of rate-limiting enzyme (M-CPTⅠ) and key enzyme of fatty acid (MCAD) in the CAR group compared with CAA group (P<0.05). Conclusion: Pressure overload-induced hypertrophy in CAA rats causes the reversion back towards fetal enery metabolism, that is, downregulates the expressions of rate-limiting enzyme and key enzyme of fatty acid oxidation. The intervention therapy with carvedilol, a vasodilating alpha- and beta-adrenoreceptor antagonist, attenuates the reversion of the metabolic gene expression to fetal type through upregulating M-CPTⅠ and MCAD mRNA expressions. Thus, carvedilol may exert cardioprotective effects on heart failure by the mechanism of preserving the adult metabolic gene regulation.

  17. Autonomous Extracellular Matrix Remodeling Controls a Progressive Adaptation in Muscle Stem Cell Regenerative Capacity during Development

    Directory of Open Access Journals (Sweden)

    Matthew Timothy Tierney

    2016-03-01

    Full Text Available Muscle stem cells (MuSCs exhibit distinct behavior during successive phases of developmental myogenesis. However, how their transition to adulthood is regulated is poorly understood. Here, we show that fetal MuSCs resist progenitor specification and exhibit altered division dynamics, intrinsic features that are progressively lost postnatally. After transplantation, fetal MuSCs expand more efficiently and contribute to muscle repair. Conversely, niche colonization efficiency increases in adulthood, indicating a balance between muscle growth and stem cell pool repopulation. Gene expression profiling identified several extracellular matrix (ECM molecules preferentially expressed in fetal MuSCs, including tenascin-C, fibronectin, and collagen VI. Loss-of-function experiments confirmed their essential and stage-specific role in regulating MuSC function. Finally, fetal-derived paracrine factors were able to enhance adult MuSC regenerative potential. Together, these findings demonstrate that MuSCs change the way in which they remodel their microenvironment to direct stem cell behavior and support the unique demands of muscle development or repair.

  18. Cell cycle regulation and cytoskeletal remodelling are critical processes in the nutritional programming of embryonic development.

    Directory of Open Access Journals (Sweden)

    Angelina Swali

    Full Text Available Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream phenotypic effects. By using a cross-over design of two well established models of maternal protein and iron restriction we aimed to identify putative common "gatekeepers" which may drive nutritional programming.Both protein and iron deficiency in utero reduced the nephron complement in adult male Wistar and Rowett Hooded Lister rats (P<0.05. This occurred in the absence of damage to the glomerular ultrastructure. Microarray, proteomic and pathway analyses identified diet-specific and strain-specific gatekeeper genes, proteins and processes which shared a common association with the regulation of the cell cycle, especially the G1/S and G2/M checkpoints, and cytoskeletal remodelling. A cell cycle-specific PCR array confirmed the down-regulation of cyclins with protein restriction and the up-regulation of apoptotic genes with iron deficiency.The timing and experimental design of this study have been carefully controlled to isolate the common molecular mechanisms which may initiate the sequelae of events involved in nutritional programming of embryonic development. We propose that despite differences in the individual genes and proteins affected in each strain and with each diet, the general response to nutrient deficiency in utero is perturbation of the cell cycle, at the level of interaction with the cytoskeleton and the mitotic checkpoints, thereby diminishing control over the integrity of DNA which is allowed to replicate. These findings offer novel

  19. Anterior Hox Genes in Cardiac Development and Great Artery Patterning

    Directory of Open Access Journals (Sweden)

    Brigitte Laforest

    2014-03-01

    Full Text Available During early development, the heart tube grows by progressive addition of progenitor cells to the arterial and venous poles. These cardiac progenitor cells, originally identified in 2001, are located in the splanchnic mesoderm in a region termed the second heart field (SHF. Since its discovery, our view of heart development has been refined and it is well established that perturbation in the addition of SHF cells results in a spectrum of congenital heart defects. We have previously shown that anterior Hox genes, including Hoxb1, Hoxa1 and Hoxa3, are expressed in distinct subdomains of the SHF that contribute to atrial and subpulmonary myocardium. It is well known that Hox proteins exert their function through interaction with members of the TALE family, including Pbx and Meis factors. The expression profile of Pbx and Meis factors overlaps with that of anterior Hox factors in the embryonic heart, and recent data suggest that they may interact together during cardiac development. This review aims to bring together recent findings in vertebrates that strongly suggest an important function for Hox, Pbx and Meis factors in heart development and disease.

  20. The role of muscle loading on bone (Remodeling at the developing enthesis.

    Directory of Open Access Journals (Sweden)

    Alexander M Tatara

    Full Text Available Muscle forces are necessary for the development and maintenance of a mineralized skeleton. Removal of loads leads to malformed bones and impaired musculoskeletal function due to changes in bone (remodeling. In the current study, the development of a mineralized junction at the interface between muscle and bone was examined under normal and impaired loading conditions. Unilateral mouse rotator cuff muscles were paralyzed using botulinum toxin A at birth. Control groups consisted of contralateral shoulders injected with saline and a separate group of normal mice. It was hypothesized that muscle unloading would suppress bone formation and enhance bone resorption at the enthesis, and that the unloading-induced bony defects could be rescued by suppressing osteoclast activity. In order to modulate osteoclast activity, mice were injected with the bisphosphonate alendronate. Bone formation was measured at the tendon enthesis using alizarin and calcein fluorescent labeling of bone surfaces followed by quantitative histomorphometry of histologic sections. Bone volume and architecture was measured using micro computed tomography. Osteoclast surface was determined via quantitative histomorphometry of tartrate resistant acid phosphatase stained histologic sections. Muscle unloading resulted in delayed initiation of endochondral ossification at the enthesis, but did not impair bone formation rate. Unloading led to severe defects in bone volume and trabecular bone architecture. These defects were partially rescued by suppression of osteoclast activity through alendronate treatment, and the effect of alendronate was dose dependent. Similarly, bone formation rate was increased with increasing alendronate dose across loading groups. The bony defects caused by unloading were therefore likely due to maintained high osteoclast activity, which normally decreases from neonatal through mature timepoints. These results have important implications for the treatment of

  1. Remodeling of the Nuclear Envelope and Lamina during Bovine Preimplantation Development and Its Functional Implications.

    Directory of Open Access Journals (Sweden)

    Jens Popken

    Full Text Available The present study demonstrates a major remodeling of the nuclear envelope and its underlying lamina during bovine preimplantation development. Up to the onset of major embryonic genome activation (MGA at the 8-cell stage nuclei showed a non-uniform distribution of nuclear pore complexes (NPCs. NPCs were exclusively present at sites where DNA contacted the nuclear lamina. Extended regions of the lamina, which were not contacted by DNA, lacked NPCs. In post-MGA nuclei the whole lamina was contacted rather uniformly by DNA. Accordingly, NPCs became uniformly distributed throughout the entire nuclear envelope. These findings shed new light on the conditions which control the integration of NPCs into the nuclear envelope. The switch from maternal to embryonic production of mRNAs was accompanied by multiple invaginations covered with NPCs, which may serve the increased demands of mRNA export and protein import. Other invaginations, as well as interior nuclear segments and vesicles without contact to the nuclear envelope, were exclusively positive for lamin B. Since the abundance of these invaginations and vesicles increased in concert with a massive nuclear volume reduction, we suggest that they reflect a mechanism for fitting the nuclear envelope and its lamina to a shrinking nuclear size during bovine preimplantation development. In addition, a deposit of extranuclear clusters of NUP153 (a marker for NPCs without associated lamin B was frequently observed from the zygote stage up to MGA. Corresponding RNA-Seq data revealed deposits of spliced, maternally provided NUP153 mRNA and little unspliced, newly synthesized RNA prior to MGA, which increased strongly at the initiation of embryonic expression of NUP153 at MGA.

  2. Tear me down: Role of calpain in the development of cardiac ventricular hypertrophy

    OpenAIRE

    Patterson, Cam; Portbury, Andrea; Schisler, Jonathan C; Willis, Monte S.

    2011-01-01

    Cardiac hypertrophy develops most commonly in response to hypertension and is an independent risk factor for the development of heart failure. The mechanisms by which cardiac hypertrophy may be reversed to reduce this risk have not been fully determined to the point where mechanism-specific therapies have been developed. Recently, proteases in the calpain family have been implicated in regulating the development of cardiac hypertrophy in preclinical animal models. In this review, we summarize...

  3. Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Engstrøm, Thomas; Mathiasen, Anders B;

    2012-01-01

    To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred and...

  4. Myocardial area at risk after ST-elevation myocardial infarction measured with the late gadolinium enhancement after scar remodeling and T2-weighted cardiac magnetic resonance imaging

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Engstrøm, Thomas; Mathiasen, Anders B;

    2011-01-01

    To evaluate the myocardial area at risk (AAR) measured by the endocardial surface area (ESA) method on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) when applied after scar remodeling (3 months after index infarction) compared to T2-weighted CMR imaging. One hundred and...

  5. The development and testing of the nurses' cardiac triage instrument.

    Science.gov (United States)

    Arslanian-Engoren, Cynthia; Hagerty, Bonnie M

    2013-01-01

    Rapid recognition and treatment of myocardial infarction (MI) reduces morbidity and mortality. Although emergency department (ED) nurses are often the first provider to evaluate individuals and are in a prime position to initiate MI guideline recommendations, no valid and reliable instrument was found to quantify their decision-making processes. The purpose of this study was to develop and test the psychometric properties of a new theoretically driven, empirically based instrument for measuring nurses' cardiac triage decisions. Using a descriptive research design, data were collected using a mailed survey. There were 158 ED nurses who completed a mailed questionnaire. Factor analysis revealed three factors (patient presentation, unbiased nurse reasoning process, and nurse action) with good internal consistency (Cronbach's alpha = .903, .809, .718) and sample adequacy (KMO = .758) of the 30-item instrument. The newly developed instrument has the potential to improve patient outcomes surrounding early MI identification and treatment. PMID:23923344

  6. Anatomy and development of the cardiac lymphatic vasculature: Its role in injury and disease.

    Science.gov (United States)

    Norman, Sophie; Riley, Paul R

    2016-04-01

    Lymphatic vessels are present throughout the entire body in all mammals and function to regulate tissue fluid balance, lipid transport and survey the immune system. Despite the presence of an extensive lymphatic plexus within the heart, until recently the importance of the cardiac lymphatic vasculature and its origins were unknown. Several studies have described the basic anatomy of the developing cardiac lymphatic vasculature and more recently the detailed development of the murine cardiac lymphatics has been documented, with important insight into their cellular sources during embryogenesis. In this review we initially describe the development of systemic lymphatic vasculature, to provide the background for a comparative description of the spatiotemporal development of the cardiac lymphatic vessels, including detail of both canonical, typically venous, and noncanonical (hemogenic endothelium) cellular sources. Subsequently, we address the response of the cardiac lymphatic network to myocardial infarction (heart attack) and the therapeutic potential of targeting cardiac lymphangiogenesis. PMID:26443964

  7. Current development of cardiac imaging with multidetector-row CT

    International Nuclear Information System (INIS)

    Multidector-row CT (MDCT) with retrospective ECG gating allows scanning the entire heart with 1.25 mm slice thickness and 250 ms effective exposure time within 35 s investigation time. The resulting images allow for an accurate high-resolution assessment of morphological detail of both the coronary arteries and the cardiac chambers. Performing a contrast-enhanced MDCT angiography (MD-CTA) in addition to a non-enhanced scan for the detection and quantification of coronary calcifications may be indicated in patients with atypical chest pain and in young patients with high cardiovascular risk. This group of patients may show non-calcified plaques as the first sign of their coronary artery disease. As the proximal part of the coronary arteries is well displayed by MD-CTA it also helps to delineate the course in anomalous coronary vessels. Additional information is drawn from the preoperative use of MD-CTA do determine the distance of the left internal mammarian artery to the left anterior descending coronary artery prior to minimal invasive bypass grafting. Additional indications for MD-CTA are the non-invasive follow up after venous bypass grafting, PTCA, and coronary stent interventions. MD-CTA allows following the course of the coronary vessels to the level of third generation coronary segmental arteries. A definite diagnosis to rule out coronary artery disease can be reliably made in vessels with a diameter of 1.5 mm or greater. With MDCT a number of different atherosclerotic changes can be observed in diseased coronary arteries. Non-stenotic lesions may show tiny calcifications surrounded by large areas of irregularly distributed soft tissue. Calcifications in this type of atherosclerotic coronary artery wall changes appear as 'the tip of iceberg'. Heavy calcifications usually tend to be non-stenotic because of vessel remodelling resulting in a widening of the coronary vessel lumen. Therefore, heavy calcifications appear to act like an 'internal stent' for a

  8. Involvement of peroxisome proliferator-activated receptors in cardiac and vascular remodeling in a novel minipig model of insulin resistance and atherosclerosis induced by consumption of a high-fat/cholesterol diet

    OpenAIRE

    Yongming, Pan; Zhaowei, Cai; Yichao, Ma; Keyan, Zhu; Liang, Chen; Fangming, Chen; Xiaoping, Xu; Quanxin, Ma; Minli, Chen

    2015-01-01

    Background A long-term high-fat/cholesterol (HFC) diet leads to insulin resistance (IR), which is associated with inflammation, atherosclerosis (AS), cardiac sympathovagal imbalance, and cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) and nuclear factor ĸB (NF-κB) are involved in the development of IR-AS. Thus, we elucidated the pathological molecular mechanism of IR-AS by feeding an HFC diet to Tibetan minipigs to induce IR and AS. Methods Male Tibetan minipigs were ...

  9. New developments in the diagnosis and management of cardiac allograft vasculopathy.

    OpenAIRE

    Mehra, M. R.; Ventura, H O; Smart, F W; Stapleton, D D; Collins, T J; Ramee, S R; Murgo, J P; White, C. J.

    1995-01-01

    The major cause of late death in cardiac transplant recipients is cardiac allograft vasculopathy, also referred to as cardiac transplant atherosclerosis, which occurs in as many as 45% of transplant recipients who survive longer than 1 year. It differs from typical atherosclerosis in that intimal hyperplasia is concentric and diffuse, the internal elastic lamina remains intact, calcification is rare, and the disease tends to develop rapidly. Intravascular ultrasound and coronary angioscopy ar...

  10. Mechanical cardiac remodeling and new-onset atrial fibrillation in long-term follow-up of subjects with chronic Chagas' disease

    Directory of Open Access Journals (Sweden)

    P.R. Benchimol-Barbosa

    2009-03-01

    Full Text Available Atrial fibrillation (AF affects subjects with Chagas' disease and is an indicator of poor prognosis. We investigated clinical, echocardiographic and electrocardiographic variables of Chagas' disease in a long-term longitudinal study as predictors of a new-onset AF episode lasting >24 h, nonfatal embolic stroke and cardiac death. Fifty adult outpatients (34 to 74 years old, 62% females staged according to the Los Andes classification were enrolled. During a follow-up of (mean ± SD 84.2 ± 39.0 months, 9 subjects developed AF (incidence: 3.3 ± 1.0%/year, 5 had nonfatal stroke (incidence: 1.3 ± 1.0%/year, and nine died (mortality rate: 2.3 ± 0.8%/year. The progression rate of left ventricular mass and left ventricular ejection fraction was significantly greater in subjects who experienced AF (16.4 ± 20.0 g/year and -8.6 ± 7.6%/year, respectively than in those who did not (8.2 ± 8.4 g/year; P = 0.03, and -3.0 ± 2.5%/year; P = 0.04, respectively. In univariate analysis, left atrial diameter ≥3.2 cm (P = 0.002, pulmonary arterial hypertension (P = 0.035, frequent premature supraventricular and ventricular contraction counts/24 h (P = 0.005 and P = 0.007, respectively, ventricular couplets/24 h (P = 0.002, and ventricular tachycardia (P = 0.004 were long-term predictors of AF. P-wave signal-averaged ECG revealed a limited long-term predictive value for AF. In chronic Chagas' disease, large left atrial diameter, pulmonary arterial hypertension, frequent supraventricular and ventricular premature beats, and ventricular tachycardia are long-term predictors of AF. The rate of left ventricular mass enlargement and systolic function deterioration impact AF incidence in this population.

  11. The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine; Kutyifa, Valentina; Ruwald, Martin H;

    2015-01-01

    AIMS: Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group. METHODS AND RESULTS...

  12. Hemodynamics, inflammation, vascular remodeling, and the development and rupture of intracranial aneurysms: a review

    Directory of Open Access Journals (Sweden)

    Francesco Signorelli

    2015-06-01

    Full Text Available The central nervous system is an immunologically active environment where several components of the immune and inflammatory response interact among them and with the constituents of nervous tissue and vasculature in a critically orchestrated manner, influencing physiologic and pathologic processes. In particular, inflammation takes a central role in the pathogenesis of intracranial aneurysms (IAs. The common pathway for aneurysm formation involves endothelial dysfunction and injury, a mounting inflammatory response, vascular smooth muscle cells (VSMCs phenotypic modulation, extracellular matrix remodeling, and subsequent cell death and vessel wall degeneration. We conducted a literature review (1980-2014 by Medline and EMBASE databases using the searching terms "IA" and "cerebral aneurysm" and further search was performed to link the search terms with the following key words: inflammation, hemodynamic(s, remodeling, macrophages, neutrophils, lymphocytes, complement, VSMCs, mast cells, cytokines, and inflammatory biomarkers. The aim of this review was to summarize the most recent and pertinent evidences regarding the articulated processes of aneurysms formation, growth, and rupture. Knowledge of these processes may guide the diagnosis and treatment of these vascular malformations, the most common cause of subarachnoid hemorrhage, which prognosis remains dismal.

  13. Pharmacotherapy in the cardiac catheterization laboratory: evolution and recent developments.

    Science.gov (United States)

    Thind, Guramrinder S; Parida, Raunak; Gupta, Nishant

    2014-01-01

    Many recent innovations have been made in developing new antiplatelet and anticoagulant drugs in the last few years, with a total of nine new antithrombotic drugs approved by the Food and Drug Administration after the year 2000. This has revolutionized the medical therapy given to manage acute coronary syndrome and support cardiac catheterization. The concept of dual antiplatelet therapy has been emphasized, and clopidogrel has emerged as the most-popular second antiplatelet drug after aspirin. Newer P2Y12 inhibitors like prasugrel and ticagrelor have been extensively studied and compared to clopidogrel. The role of glycoprotein (Gp) IIb/IIIa inhibitors is being redefined. Other alternatives to unfractionated heparin have become available, of which enoxaparin and bivalirudin have been studied the most. Apart from these, many more drugs with novel therapeutic targets are being studied and are currently under development. In this review, current evidence on these drugs is presented and analyzed in a way that would facilitate decision making for the clinician. For this analysis, various high-impact clinical trials, pharmacological studies, meta-analyses, and reviews were accessed through the MEDLINE database. Adopting a unique interdisciplinary approach, an attempt has been made to integrate pharmacological and clinical evidence to better understand and appreciate the pros and cons of each of these classes of drugs. PMID:25364258

  14. The dynamic sclera: extracellular matrix remodeling in normal ocular growth and myopia development.

    Science.gov (United States)

    Harper, Angelica R; Summers, Jody A

    2015-04-01

    Myopia is a common ocular condition, characterized by excessive elongation of the ocular globe. The prevalence of myopia continues to increase, particularly among highly educated groups, now exceeding 80% in some groups. In parallel with the increased prevalence of myopia, are increases in associated blinding ocular conditions including glaucoma, retinal detachment and macular degeneration, making myopia a significant global health concern. The elongation of the eye is closely related to the biomechanical properties of the sclera, which in turn are largely dependent on the composition of the scleral extracellular matrix. Therefore an understanding of the cellular and extracellular events involved in the regulation of scleral growth and remodeling during childhood and young adulthood will provide future avenues for the treatment of myopia and its associated ocular complications. PMID:25819458

  15. 先心病心脏重构患者血清血管紧张素转化酶2水平研究%The Serum Levels of Angiotensin-converting Enzyme2 in Patients of Congenital Heart Disease with Cardiac Remodeling

    Institute of Scientific and Technical Information of China (English)

    郭玥; 吕宁; 尹小龙

    2013-01-01

    目的 观察先心病(congenital heart disease,CHD)伴心脏重构(Cardiac remodeling)患者血管紧张素转化酶2 (angiotensin-convertirg enzyrre 2,ACE2)含量和活性的变化,探讨它们与心脏重构的关系.方法 收集被确诊为先心病的患者104例, (其中无心脏重构组80例,合并心脏重构组24例),正常对照组33例.抽取受试者静脉血,应用酶联免疫吸附法(ELISA)检测血清ACE2酶含量,用比色法检测ACE2酶活性的水平,所得实验数据使用SPSS统计软件进行分析.结果 (1)正常对照组、先心病无心脏重构组、先心病心脏重构组ACE2酶含量测定值分别为(15.79± 5.03) U/L、(18.85±6.46) U/L、(14.80±4.58) U/L.正常对照组与先心病无心脏重构组比较,ACE2含量差异有统计学意义(P<0.05);正常对照组与先心病心脏重构组比较,ACE2含量无差异(P>0.05);先心病无心脏重构组与心脏重构组比较,ACE2含量差异有统计学意义(P<0.01); (2)正常对照组、先心病无心脏重构组、先心病心脏重构组ACE2酶活性测定值分别为(1.75±0.82) U/L、(1.85±0.62) U/L、(158±0.52) U/L,3组间比较差异无统计学意义(P>0.05).结论 (1)先心病无心脏重构患者血清中的ACE2酶含量显著升高; (2)先心病无心脏重构患者与心脏重构患者血清中ACE2酶活性无变化.%Objective To observe the Angiotensin-converting enzyme2 (ACE2) protein contents and activity in the serum of patients with Congenital Heart Disease (CHD) combined with cardiac remodeling (CR) , and investigate the correlation of those with cardiac remodeling. Methods 104 patients with Congenital Heart Disease and 33 normal control patients were collected. The patients with congenital heart disease were divided into 80 cases of non-cardiac remodeling group, and 24 cases of cardiac remodeling group. The serum levels of ACE2 protein were detected by enzyme-linked immunosorbent assay ( ELISA) , ACE2 activity was detected by colorimetric

  16. Trichloroethylene: a cardiac teratogen in developing chick embryos.

    Science.gov (United States)

    Loeber, C P; Hendrix, M J; Diez De Pinos, S; Goldberg, S J

    1988-12-01

    Prior studies have evaluated the teratogenicity of TCE, a contaminant of drinking water. However, none specifically examined effects of TCE on cardiogenesis. The purpose of this study was to determine if TCE is a cardiac teratogen in early embryogenesis in an avian model. Fertile White Leghorn chicken eggs were incubated under standard conditions. At stage 6, 12, 18, or 23, TCE, in concentrations of 5 to 25 microM (2 to 28 micrograms/g body weight) was injected into the air space of the egg (vol = 0.03 ml). Mineral oil and saline served as control solutions. For this double-blinded study, solutions were coded and remained so until all observations were made and recorded. Embryonic hearts (n = 1055) were examined at stage 29, 34, or 44. Gross examination was performed, followed by microdissection. Cardiac malformations were found in 7.3% of TCE-treated hearts, compared to 2.3% of saline controls (p less than 0.01), and 1.5% of mineral oil controls (p less than 0.001). No significant difference in incidence of malformations was found when comparing saline and mineral oil controls. Cardiac defects include septal defects, cor biloculare, conotruncal abnormalities, atrioventricular canal defects, and abnormal cardiac muscle. These data demonstrate that TCE is a cardiac teratogen in an avian model. PMID:3205631

  17. Pharmacotherapy in the cardiac catheterization laboratory: evolution and recent developments

    Directory of Open Access Journals (Sweden)

    Thind GS

    2014-10-01

    Full Text Available Guramrinder S Thind,1 Raunak Parida,1 Nishant Gupta2 1SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India; 2University of Texas at Houston, Houston, TX, USAAbstract: Many recent innovations have been made in developing new antiplatelet and ­anticoagulant drugs in the last few years, with a total of nine new antithrombotic drugs approved by the Food and Drug Administration after the year 2000. This has revolutionized the medical therapy given to manage acute coronary syndrome and support cardiac catheterization. The concept of dual antiplatelet therapy has been emphasized, and clopidogrel has emerged as the most-popular second antiplatelet drug after aspirin. Newer P2Y12 inhibitors like prasugrel and ticagrelor have been extensively studied and compared to clopidogrel. The role of glycoprotein (Gp IIb/IIIa inhibitors is being redefined. Other alternatives to unfractionated heparin have become available, of which enoxaparin and bivalirudin have been studied the most. Apart from these, many more drugs with novel therapeutic targets are being studied and are currently under development. In this review, current evidence on these drugs is presented and analyzed in a way that would facilitate decision making for the clinician. For this analysis, various high-impact clinical trials, pharmacological studies, meta-analyses, and reviews were accessed through the MEDLINE database. Adopting a unique interdisciplinary approach, an attempt has been made to integrate pharmacological and clinical evidence to better understand and appreciate the pros and cons of each of these classes of drugs. Keywords: acute coronary syndrome, anticoagulants, antiplatelets, percutaneous coronary intervention

  18. Accelerated cardiac remodeling in desmoplakin transgenic mice in response to endurance exercise is associated with perturbed Wnt/β-catenin signaling.

    Science.gov (United States)

    Martherus, Ruben; Jain, Rahul; Takagi, Ken; Mendsaikhan, Uzmee; Turdi, Subat; Osinska, Hanna; James, Jeanne F; Kramer, Kristen; Purevjav, Enkhsaikhan; Towbin, Jeffrey A

    2016-01-15

    Arrhythmogenic ventricular cardiomyopathy (AVC) is a frequent underlying cause for arrhythmias and sudden cardiac death especially during intense exercise. The mechanisms involved remain largely unknown. The purpose of this study was to investigate how chronic endurance exercise contributes to desmoplakin (DSP) mutation-induced AVC pathogenesis. Transgenic mice with overexpression of desmoplakin, wild-type (Tg-DSP(WT)), or the R2834H mutant (Tg-DSP(R2834H)) along with control nontransgenic (NTg) littermates were kept sedentary or exposed to a daily running regimen for 12 wk. Cardiac function and morphology were analyzed using echocardiography, electrocardiography, histology, immunohistochemistry, RNA, and protein analysis. At baseline, 4-wk-old mice from all groups displayed normal cardiac function. When subjected to exercise, all mice retained normal cardiac function and left ventricular morphology; however, Tg-DSP(R2834H) mutants displayed right ventricular (RV) dilation and wall thinning, unlike NTg and Tg-DSP(WT). The Tg-DSP(R2834H) hearts demonstrated focal fat infiltrations in RV and cytoplasmic aggregations consisting of desmoplakin, plakoglobin, and connexin 43. These aggregates coincided with disruption of the intercalated disks, intermediate filaments, and microtubules. Although Tg-DSP(R2834H) mice already displayed high levels of p-GSK3-β(Ser9) and p-AKT1(Ser473) under sedentary conditions, decrease of nuclear GSK3-β and AKT1 levels with reduced p-GSK3-β(Ser9), p-AKT1(Ser473), and p-AKT1(Ser308) and loss of nuclear junctional plakoglobin was apparent after exercise. In contrast, Tg-DSP(WT) showed upregulation of p-AKT1(Ser473), p-AKT1(Ser308), and p-GSK3-β(Ser9) in response to exercise. Our data suggest that endurance exercise accelerates AVC pathogenesis in Tg-DSP(R2834H) mice and this event is associated with perturbed AKT1 and GSK3-β signaling. Our study suggests a potential mechanism-based approach to exercise management in patients with AVC

  19. Atrial Electrical Remodeling and Sleep Disordered Breathing

    Directory of Open Access Journals (Sweden)

    Adrian Baranchuk; Diego Conde

    2013-08-01

    Full Text Available To the Editor: We read with interest the article from Bitter et al. (1 published in the last volume of JAFIB. This non-systematic review covers some of the most important physiopathological aspects of the link between sleep disordered breathing (SDB and atrial fibrillation (AFib. We do agree with the authors on the role of hypertension, endothelial dysfunction and inflammation. These topics were, to our understanding and perspective, very well covered by the authors on this review. However, despite that the authors mentioned atrial remodeling a couple of times during their review, we are not sure that this topic and specifically atrial electrical remodeling, was properly discussed and referenced. The pathophysiology linking SDB to AF is multifactorial and may involve repetitive hypoxemia, increased sympathetic drive, fluctuations in intrathoracic pressure and systemic inflammation (2. These physiologic changes may induce structural and electrical remodeling serving as a substrate to the development of AFib. An indirect marker for such electrical remodeling is the prolongation of atrial conduction time, represented by increased maximum P-wave duration in the surface ECG. In a prior study, we showed that an increased P-wave duration has been associated with SDB (3. Interatrial block (IAB, defined as a surface P-wave duration > 120 ms, was more prevalent in patients with moderate-severe SDB (34.7% SDB vs. 0% controls, p 25 were independent predictors of maximum P-wave duration (p=0.001 and p<0.001 respectively (3. Another non-invasive method to determine atrial electrical remodeling is the Signal-averaged P-wave (SAPW duration. The SAPW duration represents the average of all P-wave durations in a given number of consecutive heartbeats. We recently postulated that SAPW would be useful to identify atrial electrical remodeling in patients with severe SDB and that treatment with C-PAP for 4-6 weeks may induce reverse atrial electrical remodeling (4

  20. Development of decommissioning management system. 9. Remodeling to PC system and system verification by evaluation of real work

    International Nuclear Information System (INIS)

    When the plan of decommissioning such as nuclear fuel cycle facilities and small-scale research reactors is examined, it is necessary to select the technology and the process of the work procedure, and to optimize the index (such as the radiation dose, the cost, amount of the waste, the number of workers, and the term of works, etc.) concerning dismantling the facility. In our waste management section, Development of the decommissioning management system, which is called 'DECMAN', for the support of making the decommissioning plan is advanced. DECMAN automatically calculates the index by using the facility data and dismantling method. This paper describes the remodeling of program to the personal computer and the system verification by evaluation of real work (Dismantling of the liquor dissolver in the old JOYO Waste Treatment Facility (the old JWTF), the glove boxes in Deuterium Critical Assembly (DCA), and the incinerator in Waste Dismantling Facility (WDF)). The outline of remodeling and verification is as follows. (1) Additional function: 1) Equipment arrangement mapping, 2) Evaluation of the radiation dose by using the air dose rate, 3) I/O of data that uses EXCEL (software). (2) Comparison of work amount between calculation value and results value: The calculation value is 222.67man·hour against the result value 249.40 man·hour in the old JWTF evaluation. (3) Forecast of accompanying work is predictable to multiply a certain coefficient by the calculation value. (4) A new idea that expected the amount of the work was constructed by using the calculation value of DECMAN. (author)

  1. Bundled software development for concurrent cardiac performance modeling

    OpenAIRE

    Еремеев, Богдан Николаевич

    2014-01-01

    Tasks of timely identification and correction of cardiac disturbances are associated with searching for quantitative laws of changing hemodynamic and electrical parameters, as well as with the analysis of asynchronous concurrent processes and their interaction. To solve this problem, it was proposed to use specialized modeling complex with a combined model of the heart, which is a graphical-analytical model of the heart, where  certain graphical elements are described by local empirical model...

  2. Development of Bipotent Cardiac/Skeletal Myogenic Progenitors from MESP1+ Mesoderm

    Directory of Open Access Journals (Sweden)

    Sunny Sun-Kin Chan

    2016-01-01

    Full Text Available The branchiomeric skeletal muscles co-evolved with new chambers of the heart to enable predatory feeding in chordates. These co-evolved tissues develop from a common population in anterior splanchnic mesoderm, referred to as cardiopharyngeal mesoderm (CPM. The regulation and development of CPM are poorly understood. We describe an embryonic stem cell-based system in which MESP1 drives a PDGFRA+ population with dual cardiac and skeletal muscle differentiation potential, and gene expression resembling CPM. Using this system, we investigate the regulation of these bipotent progenitors, and find that cardiac specification is governed by an antagonistic TGFβ-BMP axis, while skeletal muscle specification is enhanced by Rho kinase inhibition. We define transcriptional signatures of the first committed CPM-derived cardiac and skeletal myogenic progenitors, and discover surface markers to distinguish cardiac (PODXL+ from the skeletal muscle (CDH4+ CPM derivatives. These tools open an accessible window on this developmentally and evolutionarily important population.

  3. Cardiac extracellular matrix proteomics: Challenges, techniques, and clinical implications.

    Science.gov (United States)

    Chang, Chia Wei; Dalgliesh, Ailsa J; López, Javier E; Griffiths, Leigh G

    2016-01-01

    Extracellular matrix (ECM) has emerged as a dynamic tissue component, providing not only structural support, but also functionally participating in a wide range of signaling events during development, injury, and disease remodeling. Investigation of dynamic changes in cardiac ECM proteome is challenging due to the relative insolubility of ECM proteins, which results from their macromolecular nature, extensive post-translational modification (PTM), and tendency to form protein complexes. Finally, the relative abundance of cellular and mitochondrial proteins in cardiac tissue further complicates cardiac ECM proteomic approaches. Recent developments of various techniques to enrich and analyze ECM proteins are playing a major role in overcoming these challenges. Application of cardiac ECM proteomics in disease tissues can further provide spatial and temporal information relevant to disease diagnosis, prognosis, treatment, and engineering of therapeutic candidates for cardiac repair and regeneration. PMID:26200932

  4. Prototype Development of an Electrical Impedance Based Simultaneous Respiratory and Cardiac Monitoring System for Gated Radiotherapy

    OpenAIRE

    Kohli, Kirpal; Liu, Jeff; Schellenberg, Devin; Karvat, Anand; Parameswaran, Ash; Grewal, Parvind; Thomas, Steven

    2014-01-01

    Background In radiotherapy, temporary translocations of the internal organs and tumor induced by respiratory and cardiac activities can undesirably lead to significantly lower radiation dose on the targeted tumor but more harmful radiation on surrounding healthy tissues. Respiratory and cardiac gated radiotherapy offers a potential solution for the treatment of tumors located in the upper thorax. The present study focuses on the design and development of simultaneous acquisition of respira...

  5. Retinol dehydrogenase, RDH1l, is essential for the heart development and cardiac performance in zebrafish

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; ZHANG Li-feng; GUI Yong-hao; SONG Hou-yan

    2013-01-01

    Background Retinoic acid (RA) is a potent signaling molecule that plays pleiotropic roles in patterning,morphogenesis,and organogenesis during embryonic development.The synthesis from retinol (vitamin A) to retinoic acid requires two sequential oxidative steps.The first step involves the oxidation of retinol to retinal through the action of retinol dehydrogenases.Retinol dehydrogenases1l (RDH1l) is a novel zebrafish retinol dehydrogenase.Herein we investigated the role of zebrafish RDH1l in heart development and cardiac performance in detail.Methods RDH1l specific morpholino was used to reduce the function of RDH1l in zebrafish.The gene expressions were observed by using whole mount in situ hybridization.Heart rates were observed and recorded under the microscope from 24 to 72 hours post fertilization (hpf).The cardiac performance was analyzed by measuring ventricular shortening fraction (VSF).Results The knock-down of RDH1l led to abnormal neural crest cells migration and reduced numbers of neural crest cells in RDH1l morphant embryos.The reduced numbers of cardiac neural crest cells also can be seen in RDH1l morphant embryos.Furthermore,the morpholino-mediated knock-down of RDH1l resulted in the abnormal heart loop.The left-right determining genes expression pattern was altered in RDH1l morphant embryos.The impaired cardiac performance was observed in RDH1l morphant embryos.Taken together,these data demonstrate that RDH1l is essential for the heart development and cardiac performance in zebrafish.Conclusions RDH1l plays a important role in the neural crest cells development,and then ultimately affects the heart loop and cardiac performance.These results show for the first time that an enzyme involved in the retinol to retinaldehyde conversion participate in the heart development and cardiac performance in zebrafish.

  6. Vitamin D and Cardiac Differentiation.

    Science.gov (United States)

    Kim, Irene M; Norris, Keith C; Artaza, Jorge N

    2016-01-01

    Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID:26827957

  7. Immunoregulation of bone remodelling

    Science.gov (United States)

    Singh, Ajai; Mehdi, Abbass A; Srivastava, Rajeshwer N; Verma, Nar Singh

    2012-01-01

    Remodeling, a continuous physiological process maintains the strength of the bones, which maintains a delicate balance between bone formation and resorption process. This review gives an insight to the complex interaction and correlation between the bone remodeling and the corresponding changes in host immunological environment and also summarises the most recent developments occuring in the understanding of this complex field. T cells, both directly and indirectly increase the expression of receptor activator of nuclear factor kB ligand (RANKL); a vital step in the activation of osteoclasts, thus positively regulates the osteoclastogenesis. Though various cytokines, chemikines, transcription factors and co-stimulatory molecules are shared by both skeletal and immune systems, but researches are being conducted to establish and analyse their role and / or control on this complex but vital process. The understanding of this part of research may open new horizons in the management of inflammatory and autoimmune diseases, resulting into bone loss and that of osteoporosis also. PMID:22837895

  8. Remodeling in the ischemic heart: the stepwise progression for heart

    Directory of Open Access Journals (Sweden)

    J.G. Mill

    2011-09-01

    Full Text Available Abstract Coronary artery disease is the leading cause of death in the developed world and in developing countries. Acute mortality from acute myocardial infarction (MI has decreased in the last decades. However, the incidence of heart failure (HF in patients with healed infarcted areas is increasing. Therefore, HF prevention is a major challenge to the health system in order to reduce healthcare costs and to provide a better quality of life. Animal models of ischemia and infarction have been essential in providing precise information regarding cardiac remodeling. Several of these changes are maladaptive, and they progressively lead to ventricular dilatation and predispose to the development of arrhythmias, HF and death. These events depend on cell death due to necrosis and apoptosis and on activation of the inflammatory response soon after MI. Systemic and local neurohumoral activation has also been associated with maladaptive cardiac remodeling, predisposing to HF. In this review, we provide a timely description of the cardiovascular alterations that occur after MI at the cellular, neurohumoral and electrical level and discuss the repercussions of these alterations on electrical, mechanical and structural dysfunction of the heart. We also identify several areas where insufficient knowledge limits the adoption of better strategies to prevent HF development in chronically infarcted individuals.

  9. Cell Cycle Regulation and Cytoskeletal Remodelling Are Critical Processes in the Nutritional Programming of Embryonic Development

    OpenAIRE

    Angelina Swali; Sarah McMullen; Helen Hayes; Lorraine Gambling; McArdle, Harry J.; Langley-Evans, Simon C

    2011-01-01

    Many mechanisms purport to explain how nutritional signals during early development are manifested as disease in the adult offspring. While these describe processes leading from nutritional insult to development of the actual pathology, the initial underlying cause of the programming effect remains elusive. To establish the primary drivers of programming, this study aimed to capture embryonic gene and protein changes in the whole embryo at the time of nutritional insult rather than downstream...

  10. cAMP Level Modulates Scleral Collagen Remodeling, a Critical Step in the Development of Myopia

    OpenAIRE

    Tao, Yijin; Pan, Miaozhen; Liu, Shufeng; Fang, Fang; Lu, Runxia; Lu, Chanyi; Zheng, Min; An, Jianhong; Xu, Hongjia; Zhao, Fuxin; Chen, Jiang-Fan; Qu, Jia; Zhou, Xiangtian

    2013-01-01

    The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP). We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and ...

  11. The morphological development of the locomotor and cardiac muscles of the migratory barnacle goose (Branta leucopsis)

    NARCIS (Netherlands)

    Bishop, CM; Butler, PJ; ElHaj, AJ; Egginton, S; Loonen, MJJE

    1996-01-01

    The masses of the locomotor and cardiac muscles of wild barnacle goose goslings, from a migratory population, were examined systematically during development and their values compared to those of pre-migratory geese. Pre-flight development was typified by approximately linear increases of body, leg,

  12. Berberine treatment prevents cardiac dysfunction and remodeling through activation of 5'-adenosine monophosphate-activated protein kinase in type 2 diabetic rats and in palmitate-induced hypertrophic H9c2 cells.

    Science.gov (United States)

    Chang, Wenguang; Zhang, Ming; Meng, Zhaojie; Yu, Yang; Yao, Fan; Hatch, Grant M; Chen, Li

    2015-12-15

    Diabetic cardiomyopathy is the major cause of death in type 2 diabetic patients. Berberine is an isoquinoline alkaloid extract from traditional chinese herbs and its hypoglycemic and hypolipidemic effects make it a promising drug for treatment of type 2 diabetes. We examined if berberine improved cardiac function and attenuated cardiac hypertrophy and fibrosis in high fat diet and streptozotocin induced-type 2 diabetic rats in vivo and reduced expression of hypertrophy markers in palmitate-induced hypertrophic H9c2 cells in vitro. Treatment of diabetic animals with berberine partially improved cardiac function and restored fasting blood insulin, fasting blood glucose, total cholesterol, and triglyceride levels to that of control. In addition, berberine treatment of diabetic animals increased cardiac 5'-adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (AKT) activation and reduced glycogen synthase kinase 3 beta (GSK3β) activation compared to control. Palmitate incubation of H9c2 cells resulted in cellular hypertrophy and decreased expression of alpha-myosin heavy chain (α-MHC) and increased expression of beta-myosin heavy chain (β-MHC) compared to controls. Berberine treatment of palmitate-incubated H9c2 cells reduced hypertrophy, increased α-MHC expression and decreased β-MHC expression. In addition, berberine treatment of palmitate-incubated H9c2 cells increased AMPK and AKT activation and reduced GSK3β activation. The presence of the AMPK inhibitor Compound C attenuated the effects of berberine. The results strongly indicate that berberine treatment may be protective against the development of diabetic cardiomyopathy. PMID:26522928

  13. Functional cooperation of spns2 and fibronectin in cardiac and lower jaw development

    Directory of Open Access Journals (Sweden)

    Yu Hisano

    2013-06-01

    The lipid mediator sphingosine-1-phosphate (S1P is a regulator of cardiac development in zebrafish, as disruption of its receptor s1pr2 or transporter spns2 causes migration defects in cardiac progenitors. To examine the genetic interaction of S1P signaling and the cell adhesion molecule fibronectin, we have established a fn;spns2 double mutant. Cardiac migration defects in fn;spns2 mutants were more severe than those in fn or spns2 mutants. We further found that the lower jaw morphology was disorganized in the fn;spns2 mutant, while it had a slightly shortened anterior–posterior distance in the ventral pharyngeal arch in fn and spns2 mutants relative to wild type. Knockdown of fn in the s1pr2 mutant, but not in the s1pr1 mutant, resulted in severe defects in cardiac migration and ventral pharyngeal arch arrangement. Further, in the background of the fn mutant, knockdown of endothelin receptor A (ednra, which was downregulated in the spns2 mutant, caused pharyngeal defects resembling those in the fn;spns2 mutant. These results strongly suggest that Spns2-S1PR2 signaling and fibronectin cooperatively regulate both cardiac and lower jaw development in zebrafish.

  14. Myocardial phospholipid remodeling under different types of load imposed during early postnatal development

    Czech Academy of Sciences Publication Activity Database

    Novák, F.; Kolář, František; Hamplová, B.; Mrnka, L.; Pelouch, Václav; Ošťádal, Bohuslav; Nováková, O.

    2009-01-01

    Roč. 58, Suppl.2 (2009), S13-S32. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : phospholipids * myocardium * postnatal development Subject RIV: CE - Biochemistry Impact factor: 1.430, year: 2009

  15. cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.

    Directory of Open Access Journals (Sweden)

    Yijin Tao

    Full Text Available The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP. We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs. Form-deprived myopia (FDM was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.

  16. Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure

    Directory of Open Access Journals (Sweden)

    Distefano Giuseppe

    2012-09-01

    Full Text Available Abstract It is well known that the natural history of chronic heart failure (CHF,regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of the heart induced by various neuro-humoral factors released by cardiac fibrocells in response to biomechanical stress connected to chronic haemodynamic overload. Typical features of myocardial remodeling are represented by cardiomyocytes hypertrophy and apoptosis, extracellular matrix alterations, mesenchymal fibrotic and phlogistic processes and by cardiac gene expression modifications with fetal genetic program reactivation. In the last years, increasing knowledge of subtle molecular and cellular mechanisms involved in myocardial remodeling has led to the discovery of some new potential therapeutic targets capable of inducing its regression. In this paper our attention is focused on the possible use of antiapoptotic and antifibrotic agents, and on the fascinating perspectives offered by the development of myocardial gene therapy and, in particular, by myocardial regenerative therapy.

  17. Thyroid hormone activates Wnt/β-catenin signaling involved in adult epithelial development during intestinal remodeling in Xenopus laevis.

    Science.gov (United States)

    Hasebe, Takashi; Fujimoto, Kenta; Kajita, Mitsuko; Ishizuya-Oka, Atsuko

    2016-08-01

    During amphibian intestinal remodeling, thyroid hormone (TH) induces some larval epithelial cells to dedifferentiate into adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian epithelium. To clarify molecular mechanisms underlying adult epithelial development, we here focus on TH response genes that are associated with the canonical Wnt pathway. Our quantitative reverse transcription plus polymerase chain reaction and immunohistochemical analyses indicate that all of the genes examined, including β-catenin, c-Myc and secreted frizzle-related protein 2 (SFRP2), are up-regulated in Xenopus laevis intestine during both natural and TH-induced metamorphosis. Moreover, immunoreactivity for nuclear β-catenin becomes detectable in adult stem cells from the start of their appearance and then increases in intensity in adult epithelial primordia derived from the stem cells, which actively proliferate and coexpress Wnt target genes c-Myc and LGR5. These expression profiles strongly suggest the involvement of the canonical Wnt pathway in the maintenance and/or proliferation of adult stem/progenitor cells. More importantly, by using organ cultures of the tadpole intestine, we have experimentally shown that the addition of exogenous SFRP2 protein to the culture medium promotes cell proliferation of the adult epithelial primordia, whereas inhibition of endogenous SFRP2 by its antibody suppresses their proliferation. The inhibition of SFRP2 suppresses larval epithelial changes in shape from simple columnar to stem-cell-like roundish cells, resulting in the failure of epithelial dedifferentiation. Thus, TH-up-regulated SFRP2 in the postembryonic intestine promotes adult stem cell development, possibly by acting as an agonist of both canonical and non-canonical Wnt signaling. PMID:27068920

  18. Crude oil exposures reveal roles for intracellular calcium cycling in haddock craniofacial and cardiac development

    Science.gov (United States)

    Sørhus, Elin; Incardona, John P.; Karlsen, Ørjan; Linbo, Tiffany; Sørensen, Lisbet; Nordtug, Trond; van der Meeren, Terje; Thorsen, Anders; Thorbjørnsen, Maja; Jentoft, Sissel; Edvardsen, Rolf B.; Meier, Sonnich

    2016-08-01

    Recent studies have shown that crude oil exposure affects cardiac development in fish by disrupting excitation-contraction (EC) coupling. We previously found that eggs of Atlantic haddock (Melanogrammus aeglefinus) bind dispersed oil droplets, potentially leading to more profound toxic effects from uptake of polycyclic aromatic hydrocarbons (PAHs). Using lower concentrations of dispersed crude oil (0.7–7 μg/L ∑PAH), here we exposed a broader range of developmental stages over both short and prolonged durations. We quantified effects on cardiac function and morphogenesis, characterized novel craniofacial defects, and examined the expression of genes encoding potential targets underlying cardiac and craniofacial defects. Because of oil droplet binding, a 24-hr exposure was sufficient to create severe cardiac and craniofacial abnormalities. The specific nature of the craniofacial abnormalities suggests that crude oil may target common craniofacial and cardiac precursor cells either directly or indirectly by affecting ion channels and intracellular calcium in particular. Furthermore, down-regulation of genes encoding specific components of the EC coupling machinery suggests that crude oil disrupts excitation-transcription coupling or normal feedback regulation of ion channels blocked by PAHs. These data support a unifying hypothesis whereby depletion of intracellular calcium pools by crude oil-derived PAHs disrupts several pathways critical for organogenesis in fish.

  19. Influence on left cardiac remodeling and left ventricular function in coronary heart disease by performing percutaneous transluminal coronary angioplasty and stent implantation and drug re-intervention therapy%冠心病PTCA+支架术及药物再干预对左心重构和左室功能的影响

    Institute of Scientific and Technical Information of China (English)

    赵文强; 王俊; 谢红珍; 吴艳君; 潘啸东

    2008-01-01

    Objective To study influence of percutaneous transluminal coronary angioplasty (PTCA) and stent implantation on left cardiac remodeling and left ventricular function and clinical effect of drug re-inter- vention in coronary heart disease. Methods 98 patients with coronary heart disease were divided into 4 groups one year after performing percutaneous coronary intervention (PCI), clinical and echocardiographic indexes of left cardiac remodeling and left ventricular function were examined by comparison of 4 groups of post-PCI versus pre-PCI, influences of different PCI strategy and different drug re-interventions on left cardiac remodeling and left cardiac function were analysed. Results NYHA cardiac function grade,6 minute's walk test,left atrial volume index( LAVI), left ventricular diastolic-end volume index (LVDEVI), eject fraction (EF), ventricular Wall movement loss fraction(WMLF) in 4 groups of post-PCI were better than those in pre-PCI(all P < 0.001). Those in 6 months group and 12 months group of post-PCI were also better than those in 1 week group of post-PCI(all P<0.01). LAVI, LVEDVI, EF and WMLF were significantly different among different groups of PCI strategy, and better by comparison of Group simvastatin and Group irbesartan versus group of routine drug, but little different by Group tirofiban versus group of routine drug in patients undergoing drug re-intervention of post-PCL Concluslan Left cardiac remodeling and left ventricular function in coronary heart disease have a significant improvement in post-PCIone year, suitable PCI strategy and drug re-intervention have further influence on bettering left cardiac remodeling and left ventricular function.%目的 研究PTCA+支架术对左心重构和左室功能的影响及药物再干预的效果.方法 对98例冠心病患者经皮冠状动脉介入治疗(PCI)术后1年内4组与术前左心重构、左室功能的临床与超声指标对比研究,对不同PCI策略和不同药物干预效应与

  20. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling

    OpenAIRE

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G.; Bezprozvanny, Ilya; Huber, Kimberly M.; Wu, Jiang I.

    2015-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nod...

  1. Computerized prediction of intensive care unit discharge after cardiac surgery: development and validation of a Gaussian processes model

    OpenAIRE

    Meyfroidt Geert; Güiza Fabian; Cottem Dominiek; De Becker Wilfried; Van Loon Kristien; Aerts Jean-Marie; Berckmans Daniël; Ramon Jan; Bruynooghe Maurice; Van den Berghe Greet

    2011-01-01

    Abstract Background The intensive care unit (ICU) length of stay (LOS) of patients undergoing cardiac surgery may vary considerably, and is often difficult to predict within the first hours after admission. The early clinical evolution of a cardiac surgery patient might be predictive for his LOS. The purpose of the present study was to develop a predictive model for ICU discharge after non-emergency cardiac surgery, by analyzing the first 4 hours of data in the computerized medical record of ...

  2. Developing Tools to Measure Quality in Congenital Catheterization and Interventions: The Congenital Cardiac Catheterization Project on Outcomes (C3PO)

    OpenAIRE

    Chaudhry-Waterman, Nadia; Coombs, Sandra; Porras, Diego; Holzer, Ralf; Bergersen, Lisa

    2014-01-01

    The broad range of relatively rare procedures performed in pediatric cardiac catheterization laboratories has made the standardization of care and risk assessment in the field statistically quite problematic. However, with the growing number of patients who undergo cardiac catheterization, it has become imperative that the cardiology community overcomes these challenges to study patient outcomes. The Congenital Cardiac Catheterization Project on Outcomes was able to develop benchmarks, tools ...

  3. Development and Validation of Predictive Models of Cardiac Mortality and Transplantation in Resynchronization Therapy

    Directory of Open Access Journals (Sweden)

    Eduardo Arrais Rocha

    2015-01-01

    Full Text Available Abstract Background: 30-40% of cardiac resynchronization therapy cases do not achieve favorable outcomes. Objective: This study aimed to develop predictive models for the combined endpoint of cardiac death and transplantation (Tx at different stages of cardiac resynchronization therapy (CRT. Methods: Prospective observational study of 116 patients aged 64.8 ± 11.1 years, 68.1% of whom had functional class (FC III and 31.9% had ambulatory class IV. Clinical, electrocardiographic and echocardiographic variables were assessed by using Cox regression and Kaplan-Meier curves. Results: The cardiac mortality/Tx rate was 16.3% during the follow-up period of 34.0 ± 17.9 months. Prior to implantation, right ventricular dysfunction (RVD, ejection fraction < 25% and use of high doses of diuretics (HDD increased the risk of cardiac death and Tx by 3.9-, 4.8-, and 5.9-fold, respectively. In the first year after CRT, RVD, HDD and hospitalization due to congestive heart failure increased the risk of death at hazard ratios of 3.5, 5.3, and 12.5, respectively. In the second year after CRT, RVD and FC III/IV were significant risk factors of mortality in the multivariate Cox model. The accuracy rates of the models were 84.6% at preimplantation, 93% in the first year after CRT, and 90.5% in the second year after CRT. The models were validated by bootstrapping. Conclusion: We developed predictive models of cardiac death and Tx at different stages of CRT based on the analysis of simple and easily obtainable clinical and echocardiographic variables. The models showed good accuracy and adjustment, were validated internally, and are useful in the selection, monitoring and counseling of patients indicated for CRT.

  4. Ontogenetic development of cardiac tolerance to oxygen deprivation – possible mechanisms

    Czech Academy of Sciences Publication Activity Database

    Ošťádal, Bohuslav; Ošťádalová, Ivana; Kolář, František; Charvátová, Zuzana; Netuka, I.

    2009-01-01

    Roč. 58, Suppl.2 (2009), S1-S12. ISSN 0862-8408 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : hypoxia/ ischemia * cardiac tolerance * ontogenetic development Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.430, year: 2009

  5. Development of the Health Incentive Program Questionnaire (HIP-Q) in a cardiac rehabilitation population

    OpenAIRE

    Mitchell, Marc S.; Goodman, Jack M; Alter, David A.; Oh, Paul I.; Guy E.J. Faulkner

    2015-01-01

    The purpose of this study was to develop a questionnaire to facilitate the design of acceptable financial health incentive programs. A multiphase psychometric questionnaire development method was used. Theoretical and literature reviews and three focus groups generated a pool of content areas and items. New items were developed to ensure adequate content coverage. Field testing was conducted with a convenience sample of cardiac rehabilitation (CR) patients (n = 59) to establish face and const...

  6. Cardiac Remodelling in Thermally Acclimated Fish

    OpenAIRE

    Fenna, Andrew

    2013-01-01

    Fish are subject to a variety of long and short term environmental and physical insults during their life; however they manage to adapt, ensuring physiological processes remain effective, enabling the animal to thrive in a wide range of conditions. One major environmental fluctuation that can occur rapidly or over a long period of time is temperature. Teleost fish, such as the rainbow trout (Oncorhynchus mykiss) are ectothermic, meaning their body temperature is regulated by environmental tem...

  7. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis

    Science.gov (United States)

    Jung, Joanna; Dyck, Jason R. B.; Lopaschuk, Gary D.; Agellon, Luis B.; Michalak, Marek

    2016-01-01

    Background Cardiac fibrosis attributed to excessive deposition of extracellular matrix proteins is a major cause of heart failure and death. Cardiac fibrosis is extremely difficult and challenging to treat in a clinical setting due to lack of understanding of molecular mechanisms leading to cardiac fibrosis and effective anti-fibrotic therapies. The objective in this study was to examine whether unfolded protein response (UPR) pathway mediates cardiac fibrosis and whether a pharmacological intervention to modulate UPR can prevent cardiac fibrosis and preserve heart function. Methodology/Principal Findings We demonstrate here that the mechanism leading to development of fibrosis in a mouse with increased expression of calreticulin, a model of heart failure, stems from impairment of endoplasmic reticulum (ER) homeostasis, transient activation of the unfolded protein response (UPR) pathway and stimulation of the TGFβ1/Smad2/3 signaling pathway. Remarkably, sustained pharmacologic inhibition of the UPR pathway by tauroursodeoxycholic acid (TUDCA) is sufficient to prevent cardiac fibrosis, and improved exercise tolerance. Conclusions We show that the mechanism leading to development of fibrosis in a mouse model of heart failure stems from transient activation of UPR pathway leading to persistent remodelling of cardiac tissue. Blocking the activation of the transiently activated UPR pathway by TUDCA prevented cardiac fibrosis, and improved prognosis. These findings offer a window for additional interventions that can preserve heart function. PMID:27441395

  8. Effect of simvastatin on cardiac function and left ventricular remodeling in patients with heart failure%辛伐他汀对心力衰竭患者心脏功能及左心室重构的影响

    Institute of Scientific and Technical Information of China (English)

    李国锋; 孙立伟; 黎笑冰

    2011-01-01

    Objectives To observing the effect of simvastatin on cardiac function and left ventricular remodeling in patients with heart failure. Methods Sixty one cases with non-ischemic heart failure were randomly divided into observation group (n=30) and control group (n=31 ) in The People's Hospital of Dongguan from Jan 2008 to Jul 2009. The two groups were given conventional therapy. Observation group was given simvastatin 20 mg/d in a course of 6 months. Heart function and biochemical changes of the two groups were observed and compared. Results After 6 months of treatment, the New York Heart Association (NYHA) classification [(2.0±0.4) grade vs. (2.5±0.4) grade, P<0.01 ]and left ventricular ejection fraction (LVEF)[58.7% ± 5.2% vs. 43.0% ± 5.7%, P<0.01 ]of observation group were improved significantly (P<0.01). NYHA classification of control group was improved [(2.1 ±0.4) grade vs. (2.4±0.4) grade, P<0.05]. LVEF of control group showed improved tendence, but had no significance (47.6% ± 5.3% vs. 40.9% ± 6.3%, P=0.052). Conclusions Patients with non-ischemic heart failure treated with simvastatin on the base of conventional treatment can significantly improve cardiac function and left ventricular remodeling, and it is safe and effective.%目的 观察小剂量辛伐他汀对心力衰竭患者心脏功能及左心室重构的影响.方法 选取2008年1月至2009年7月东莞市人民医院确诊为非缺血性心力衰竭的患者61例为研究对象.按电脑随机数字表法将入选对象分为观察组(n=30)与对照组(n=31),观察组在标准心力衰竭治疗基础上加服辛伐他汀(20 mg/d,治疗期6个月).比较两组治疗前后患者心脏功能、生化指标的变化.结果 经过6个月的治疗,观察组纽约心脏协会心功能分级[(2.0±0.4)级vs.(2.5±0.4)级,P<0.01]和左心室射血分数(58.7%±5.2% vs.43.0%±5.7%,P<0.01)显著改善,差异有统计学意义;对照组纽约心脏协会心功能

  9. Comparative Characterization of Cardiac Development Specific microRNAs: Fetal Regulators for Future

    OpenAIRE

    Rustagi, Yashika; Jaiswal, Hitesh K.; Rawal, Kamal; Kundu, Gopal C.; Rani, Vibha

    2015-01-01

    MicroRNAs (miRNAs) are small, conserved RNAs known to regulate several biological processes by influencing gene expression in eukaryotes. The implication of miRNAs as another player of regulatory layers during heart development and diseases has recently been explored. However, there is no study which elucidates the profiling of miRNAs during development of heart till date. Very limited miRNAs have been reported to date in cardiac context. In addition, integration of large scale experimental d...

  10. Changes in short-chain acyl-coA dehydrogenase during rat cardiac development and stress

    OpenAIRE

    Huang, Jinxian; Xu, Lipeng; Huang, Qiuju; Luo, Jiani; Liu, Peiqing; Chen, Shaorui; Yuan, Xi; Lu, Yao; Wang, Ping; Zhou, Sigui

    2015-01-01

    This study was designed to investigate the expression of short-chain acyl-CoA dehydrogenase (SCAD), a key enzyme of fatty acid β-oxidation, during rat heart development and the difference of SCAD between pathological and physiological cardiac hypertrophy. The expression of SCAD was lowest in the foetal and neonatal heart, which had time-dependent increase during normal heart development. In contrast, a significant decrease in SCAD expression was observed in different ages of spontaneously hyp...

  11. Development of a Customized Database Management System for the Cardiac Catheterization Laboratory

    OpenAIRE

    MILLER, MICHAEL R.

    1980-01-01

    A simple database management system has been developed for use by the Cardiac Catheterization Laboratory at University of Iowa Hospitals and Clinics. The system was developed with limited resources in a period of eight months. Major functions provided by the DBMS are data acquisition, report generation and selective retrieval by diagnosis. The modular design of the system provides for growth in the database without modification of existing programs. The project was divided into four stages: d...

  12. Development of aerobic and anaerobic metabolism in cardiac and skeletal muscles from harp and hooded seals.

    Science.gov (United States)

    Burns, J M; Skomp, N; Bishop, N; Lestyk, K; Hammill, M

    2010-03-01

    In diving animals, skeletal muscle adaptations to extend underwater time despite selective vasoconstriction include elevated myoglobin (Mb) concentrations, high acid buffering ability (beta) and high aerobic and anaerobic enzyme activities. However, because cardiac muscle is perfused during dives, it may rely less heavily on Mb, beta and anaerobic pathways to support contractile activity. In addition, because cardiac tissue must sustain contractile activity even before birth, it may be more physiologically mature at birth and/or develop faster than skeletal muscles. To test these hypotheses, we measured Mb levels, beta and the activities of citrate synthase (CS), beta-hydroxyacyl-CoA dehydrogenase (HOAD) and lactate dehydrogenase (LDH) in cardiac and skeletal muscle samples from 72 harp and hooded seals, ranging in age from fetuses to adults. Results indicate that in adults cardiac muscle had lower Mb levels (14.7%), beta (55.5%) and LDH activity (36.2%) but higher CS (459.6%) and HOAD (371.3%) activities (all Pseals had significantly lower [Mb] (44.7%) beta (80.7%) and LDH activity (89.5%) than adults (all Pseal hearts do not exhibit unique adaptations to the challenges of an aquatic existence. PMID:20154189

  13. Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.

    Science.gov (United States)

    Xavier-Neto, José; Sousa Costa, Ângela M; Figueira, Ana Carolina M; Caiaffa, Carlo Donato; Amaral, Fabio Neves do; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R; Castillo, Hozana Andrade

    2015-02-01

    Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development. PMID:25134739

  14. SIGNALLING THROUGH RETINOIC ACID RECEPTORS IN CARDIAC DEVELOPMENT: DOING THE RIGHT THINGS AT THE RIGHT TIMES

    Science.gov (United States)

    Xavier-Neto, José; Costa, Ângela M. Sousa; Figueira, Ana Carolina M.; Caiaffa, Carlo Donato; do Amaral, Fabio Neves; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R.; Castillo, Hozana Andrade

    2015-01-01

    Retinoic acid (RA) is a terpenoid that is synthesized from Vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinic and experimental data provide uncontested evidence for the pleiotropic roles of RA signalling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signalling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signalling is exquisitely regulated according to specific phases of cardiac development and that RA signalling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signalling by RA receptors (RARs) in early phases of heart development. PMID:25134739

  15. Pharmacotherapy in the cardiac catheterization laboratory: evolution and recent developments

    OpenAIRE

    Thind GS; Parida R; Gupta N

    2014-01-01

    Guramrinder S Thind,1 Raunak Parida,1 Nishant Gupta2 1SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India; 2University of Texas at Houston, Houston, TX, USAAbstract: Many recent innovations have been made in developing new antiplatelet and ­anticoagulant drugs in the last few years, with a total of nine new antithrombotic drugs approved by the Food and Drug Administration after the year 2000. This has revolutionized the medical therapy given to manage acute coronary sy...

  16. Ciona intestinalis as a model for cardiac development

    OpenAIRE

    Davidson, Brad

    2006-01-01

    The primitive chordate Ciona intestinalis has emerged as a significant model system for the study of heart development. The Ciona embryo employs a conserved heart gene network in the context of extremely low cell numbers and reduced genetic redundancy. Here, I review recent studies on the molecular genetics of Ciona cardiogenesis as well as classic work on heart anatomy and physiology. I also discuss the potential of employing Ciona to decipher a comprehensive chordate gene network and to det...

  17. Pre-ICU characteristics in cardiac surgery patients with CPB developing AKI

    OpenAIRE

    Mertens, K.; Pennemans, Valerie; Penders, Joris; Swennen, Quirine; Vander Laenen, M.; Vanelderen, P.; Boer, Willem

    2014-01-01

    Aims. AKI is common after cardiac surgery involving CPB. Lack of reliable early detection methods for post-op AKI limits timely therapeutic intervention. A number of new biomarkers for AKI await validation in this setting. Analysis of a database was performed to define baseline patient and biomarker characteristics in patients developing AKI. Methods. 259 patients were enrolled. Patients with severe pre-existing renal insufficiency were excluded (eGFR

  18. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    Directory of Open Access Journals (Sweden)

    Quan He

    2014-01-01

    Full Text Available Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.

  19. Mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes.

    Science.gov (United States)

    He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

    2014-01-01

    Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

  20. Cardiac electrical stunning is a common feature of cardiac arrhythmias.

    Science.gov (United States)

    Li, Guangping; Liu, Tong; Liu, Enzhao

    2006-01-01

    There are many published papers focused on the topic of atrial electrical remodeling, which defined as the shortening and dispersion of effective refractory period (ERP) in patients with paroxysmal or persistent tachyarrhythmias or in animals with long-term rapid atrial pacing. Heart failure could produce the electrical remodeling of sinus node, manifesting the prolongation of corrected sinus node recovery time and sinus cycle length. It might be attributed to decreased hyperpolarization-activated cyclic nucleotide expression of sinus node. Rapid atrial pacing for only 10-15 min, simulating transient atrial tachyarrhythmias, alters sinus node function in human. Termination of atrial flutter by ablation induces reversible changes in sinus node function. After atrial fibrillation (AF) ablation, there was a significant improvement of sinus node function, with an increase in the mean heart rate, maximal heart rate and heart rate range significantly. Reverse electrical remodeling of the ERP occurs at different rates in different regions of the atrium. Previous experiments showed that electrical remodeling of atrial myocardium could be induced by autonomic nervous transmitters and suggested that autonomic nerve activity was an important factor to promote AF episodes. We postulated that electrical remodeling and reverse electrical remodeling are common features of the heart, including atrium, ventricle, sinus node, and conductive system. Inappropriate very rapid or slow electrical depolarization may cause electrical remodeling of the heart, but appropriate rates of electrical depolarization and cessation of rapid stimulation may contribute to the reverse electrical remodeling. So, we forward that a concept defined as cardiac electrical stunning, including electrical remodeling and reverse electrical remodeling, should be a common characteristic and mechanism of cardiac arrhythmias. PMID:16759818

  1. Ah Receptor Signaling Controls the Expression of Cardiac Development and Homeostasis Genes.

    Science.gov (United States)

    Carreira, Vinicius S; Fan, Yunxia; Wang, Qing; Zhang, Xiang; Kurita, Hisaka; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-10-01

    Congenital heart disease (CHD) is the most common congenital abnormality and one of the leading causes of newborn death throughout the world. Despite much emerging scientific information, the precise etiology of this disease remains elusive. Here, we show that the aryl hydrocarbon receptor (AHR) regulates the expression of crucial cardiogenesis genes and that interference with endogenous AHR functions, either by gene ablation or by agonist exposure during early development, causes overlapping structural and functional cardiac abnormalities that lead to altered fetal heart physiology, including higher heart rates, right and left ventricle dilation, higher stroke volume, and reduced ejection fraction. With striking similarity between AHR knockout (Ahr(-/-)) and agonist-exposed wild type (Ahr(+/+)) embryos, in utero disruption of endogenous AHR functions converge into dysregulation of molecular mechanisms needed for attainment and maintenance of cardiac differentiation, including the pivotal signals regulated by the cardiogenic transcription factor NKH2.5, energy balance via oxidative phosphorylation and TCA cycle and global mitochondrial function and homeostasis. Our findings suggest that AHR signaling in the developing mammalian heart is central to the regulation of pathways crucial for cellular metabolism, cardiogenesis, and cardiac function, which are potential targets of environmental factors associated with CHD. PMID:26139165

  2. The role of Wnt regulation in heart development, cardiac repair and disease: A tissue engineering perspective.

    Science.gov (United States)

    Pahnke, Aric; Conant, Genna; Huyer, Locke Davenport; Zhao, Yimu; Feric, Nicole; Radisic, Milica

    2016-05-01

    Wingless-related integration site (Wnt) signaling has proven to be a fundamental mechanism in cardiovascular development as well as disease. Understanding its particular role in heart formation has helped to develop pluripotent stem cell differentiation protocols that produce relatively pure cardiomyocyte populations. The resultant cardiomyocytes have been used to generate heart tissue for pharmaceutical testing, and to study physiological and disease states. Such protocols in combination with induced pluripotent stem cell technology have yielded patient-derived cardiomyocytes that exhibit some of the hallmarks of cardiovascular disease and are therefore being used to model disease states. While FDA approval of new treatments typically requires animal experiments, the burgeoning field of tissue engineering could act as a replacement. This would necessitate the generation of reproducible three-dimensional cardiac tissues in a well-controlled environment, which exhibit native heart properties, such as cellular density, composition, extracellular matrix composition, and structure-function. Such tissues could also enable the further study of Wnt signaling. Furthermore, as Wnt signaling has been found to have a mechanistic role in cardiac pathophysiology, e.g. heart attack, hypertrophy, atherosclerosis, and aortic stenosis, its strategic manipulation could provide a means of generating reproducible and specific, physiological and pathological cardiac models. PMID:26626076

  3. Development and evaluation of a treadmill-based exercise tolerance test in cardiac rehabilitation.

    Science.gov (United States)

    Dunagan, Julie; Adams, Jenny; Cheng, Dunlei; Barton, Stephanie; Bigej-Cerqua, Janet; Mims, Lisa; Molden, Jennifer; Anderson, Valerie

    2013-07-01

    Cardiac rehabilitation exercise prescriptions should be based on exercise stress tests; however, limitations in performing stress tests in this setting typically force reliance on subjective measures like the Duke Activity Status Index (DASI). We developed and evaluated a treadmill-based exercise tolerance test (ETT) to provide objective physiologic measures without requiring additional equipment or insurance charges. The ETT is stopped when the patient's Borg scale rating of perceived exertion (RPE) reaches 15 or when any sign/symptom indicates risk of an adverse event. Outcomes of the study included reasons for stopping; maximum heart rate, systolic blood pressure, and rate pressure product; and adverse events. We tested equivalence to the DASI as requiring the 95% confidence interval for the mean difference between DASI and ETT metabolic equivalents (METs) to fall within the range (-1, 1). Among 502 consecutive cardiac rehabilitation patients, one suffered a panic attack; no other adverse events occurred. Most (80%) stopped because they reached an RPE of 15; the remaining 20% were stopped on indications that continuing risked an adverse event. Mean maximum systolic blood pressure, heart rate, and rate pressure product were significantly (P pressure products remained below 36,000. The mean difference between DASI and ETT METs was -0.8 (-0.98, -0.65), indicating equivalence at our threshold. In conclusion, the ETT can be performed within cardiac rehabilitation, providing a functional capacity assessment equivalent to the DASI and objective physiologic measures for developing exercise prescriptions and measuring progress. PMID:23814381

  4. Cardiac deletion of Smyd2 is dispensable for mouse heart development.

    Directory of Open Access Journals (Sweden)

    Florian Diehl

    Full Text Available Chromatin modifying enzymes play a critical role in cardiac differentiation. Previously, it has been shown that the targeted deletion of the histone methyltransferase, Smyd1, the founding member of the SET and MYND domain containing (Smyd family, interferes with cardiomyocyte maturation and proper formation of the right heart ventricle. The highly related paralogue, Smyd2 is a histone 3 lysine 4- and lysine 36-specific methyltransferase expressed in heart and brain. Here, we report that Smyd2 is differentially expressed during cardiac development with highest expression in the neonatal heart. To elucidate the functional role of Smyd2 in the heart, we generated conditional knockout (cKO mice harboring a cardiomyocyte-specific deletion of Smyd2 and performed histological, functional and molecular analyses. Unexpectedly, cardiac deletion of Smyd2 was dispensable for proper morphological and functional development of the murine heart and had no effect on global histone 3 lysine 4 or 36 methylation. However, we provide evidence for a potential role of Smyd2 in the transcriptional regulation of genes associated with translation and reveal that Smyd2, similar to Smyd3, interacts with RNA Polymerase II as well as to the RNA helicase, HELZ.

  5. Tomoregulin-1 prevents cardiac hypertrophy after pressure overload in mice by inhibiting TAK1-JNK pathways

    Directory of Open Access Journals (Sweden)

    Dan Bao

    2015-08-01

    Full Text Available Cardiac hypertrophy is associated with many forms of heart disease, and identifying important modifier genes involved in the pathogenesis of cardiac hypertrophy could lead to the development of new therapeutic strategies. Tomoregulin-1 is a growth factor that is primarily involved in embryonic development and adult central nervous system (CNS function, and it is expressed abnormally in a variety of CNS pathologies. Tomoregulin-1 is also expressed in the myocardium. However, the effects of tomoregulin-1 on the heart, particularly on cardiac hypertrophy, remains unknown. The aim of the study is to examine whether and by what mechanism tomoregulin-1 regulates the development of cardiac hypertrophy induced by pressure overload. In this study, we found that tomoregulin-1 was significantly upregulated in two cardiac hypertrophy models: cTnTR92Q transgenic mice and thoracic aorta constriction (TAC-induced cardiac hypertrophy mice. The transgenic overexpression of tomoregulin-1 increased the survival rate, improved the cardiac geometry and functional parameters of echocardiography, and decreased the degree of cardiac hypertrophy of the TAC mice, whereas knockdown of tomoregulin-1 expression resulted in an opposite phenotype and exacerbated phenotypes of cardiac hypertrophy induced by TAC. A possible mechanism by which tomoregulin-1 regulates the development of cardiac hypertrophy in TAC-induced cardiac hypertrophy is through inhibiting TGFβ non-canonical (TAK1-JNK pathways in the myocardium. Tomoregulin-1 plays a protective role in the modulation of adverse cardiac remodeling from pressure overload in mice. Tomoregulin-1 could be a therapeutic target to control the development of cardiac hypertrophy.

  6. Recipient-derived EDA fibronectin promotes cardiac allograft fibrosis.

    Science.gov (United States)

    Booth, Adam J; Wood, Sherri C; Cornett, Ashley M; Dreffs, Alyssa A; Lu, Guanyi; Muro, Andrés F; White, Eric S; Bishop, D Keith

    2012-03-01

    Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA(-/-)) and wild-type (WT) mice. While EDA(-/-) mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA(-/-) mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which enhance

  7. Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial

    DEFF Research Database (Denmark)

    Daubert, Claude; Gold, Michael R; Abraham, William T;

    2009-01-01

    dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left v...

  8. Biomimetic material strategies for cardiac tissue engineering

    International Nuclear Information System (INIS)

    Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.

  9. SU-E-J-129: Atlas Development for Cardiac Automatic Contouring Using Multi-Atlas Segmentation

    International Nuclear Information System (INIS)

    Purpose: To develop a set of atlases for automatic contouring of cardiac structures to determine heart radiation dose and the associated toxicity. Methods: Six thoracic cancer patients with both contrast and non-contrast CT images were acquired for this study. Eight radiation oncologists manually and independently delineated cardiac contours on the non-contrast CT by referring to the fused contrast CT and following the RTOG 1106 atlas contouring guideline. Fifteen regions of interest (ROIs) were delineated, including heart, four chambers, four coronary arteries, pulmonary artery and vein, inferior and superior vena cava, and ascending and descending aorta. Individual expert contours were fused using the simultaneous truth and performance level estimation (STAPLE) algorithm for each ROI and each patient. The fused contours became atlases for an in-house multi-atlas segmentation. Using leave-one-out test, we generated auto-segmented contours for each ROI and each patient. The auto-segmented contours were compared with the fused contours using the Dice similarity coefficient (DSC) and the mean surface distance (MSD). Results: Inter-observer variability was not obvious for heart, chambers, and aorta but was large for other structures that were not clearly distinguishable on CT image. The average DSC between individual expert contours and the fused contours were less than 50% for coronary arteries and pulmonary vein, and the average MSD were greater than 4.0 mm. The largest MSD of expert contours deviating from the fused contours was 2.5 cm. The mean DSC and MSD of auto-segmented contours were within one standard deviation of expert contouring variability except the right coronary artery. The coronary arteries, vena cava, and pulmonary vein had DSC<70% and MSD>3.0 mm. Conclusion: A set of cardiac atlases was created for cardiac automatic contouring, the accuracy of which was comparable to the variability in expert contouring. However, substantial modification may need

  10. Leptin as a mediator between obesity and cardiac dysfunction

    Directory of Open Access Journals (Sweden)

    Joanna Karbowska

    2012-05-01

    Full Text Available  Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and in­volved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue.These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

  11. Postmyocardial Infarct Remodeling and Heart Failure: Potential Contributions from Pro- and Antiaging Factors

    OpenAIRE

    Idikio, Halliday A.

    2011-01-01

    Myocardial infarction and adverse postinfarct remodeling in older persons lead to poor outcome and need greater understanding of the contributions of age-related factors on abnormal cardiac function and management. In this perspective, how normal aging processes could contribute to the events of post-myocardial infarction and remodeling is reviewed. Post-myocardial infarction and remodeling involve cardiomechanical factors and neurohormonal response. Many factors prevent or accelerate aging...

  12. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  13. Development of a New Cardiac and Torso Phantom for Verifying the Accuracy of Myocardial Perfusion SPECT

    International Nuclear Information System (INIS)

    Corrections of attenuation, scatter and resolution are important in order to improve the accuracy of single photon emission computed tomography (SPECT) image reconstruction. Especially, the heart movement by respiration and beating cause the errors in the corrections. Myocardial phantom is used to verify the correction methods, but there are many different parts in the current phantoms in actual human body. Therefore the results using a phantom are often considered apart from the clinical data. We developed a new phantom that implements the human body structure around the thorax more faithfully. The new phantom has the small mediastinum which can simulate the structure in which the lung adjoins anterior, lateral and apex of myocardium. The container was made of acrylic and water-equivalent material was used for mediastinum. In addition, solidified polyurethane foam in epoxy resin was used for lung. Five different sizes of myocardium were developed for the quantitative gated SPECT (QGS). The septa of all different cardiac phantoms were designed so that they can be located at the same position. The proposed phantom was attached with liver and gallbladder, the adjustment was respectively possible for the height of them. The volumes of five cardiac ventricles were 150.0, 137.3, 83.1, 42.7 and 38.6 ml respectively. The SPECT were performed for the new phantom, and the differences between the images were examined after the correction methods were applied. The three-dimensional tomography of myocardium was well reconstructed, and the subjective evaluations were done to show the difference among the various corrections. We developed the new cardiac and torso phantom, and the difference of various corrections was shown on SPECT images and QGS results.

  14. NDR Kinases Are Essential for Somitogenesis and Cardiac Looping during Mouse Embryonic Development.

    Directory of Open Access Journals (Sweden)

    Debora Schmitz-Rohmer

    Full Text Available Studies of mammalian tissue culture cells indicate that the conserved and distinct NDR isoforms, NDR1 and NDR2, play essential cell biological roles. However, mice lacking either Ndr1 or Ndr2 alone develop normally. Here, we studied the physiological consequences of inactivating both NDR1 and NDR2 in mice, showing that the lack of both Ndr1/Ndr2 (called Ndr1/2-double null mutants causes embryonic lethality. In support of compensatory roles for NDR1 and NDR2, total protein and activating phosphorylation levels of the remaining NDR isoform were elevated in mice lacking either Ndr1 or Ndr2. Mice retaining one single wild-type Ndr allele were viable and fertile. Ndr1/2-double null embryos displayed multiple phenotypes causing a developmental delay from embryonic day E8.5 onwards. While NDR kinases are not required for notochord formation, the somites of Ndr1/2-double null embryos were smaller, irregularly shaped and unevenly spaced along the anterior-posterior axis. Genes implicated in somitogenesis were down-regulated and the normally symmetric expression of Lunatic fringe, a component of the Notch pathway, showed a left-right bias in the last forming somite in 50% of all Ndr1/2-double null embryos. In addition, Ndr1/2-double null embryos developed a heart defect that manifests itself as pericardial edemas, obstructed heart tubes and arrest of cardiac looping. The resulting cardiac insufficiency is the likely cause of the lethality of Ndr1/2-double null embryos around E10. Taken together, we show that NDR kinases compensate for each other in vivo in mouse embryos, explaining why mice deficient for either Ndr1 or Ndr2 are viable. Ndr1/2-double null embryos show defects in somitogenesis and cardiac looping, which reveals their essential functions and shows that the NDR kinases are critically required during the early phase of organogenesis.

  15. Suppressor of IKKɛ is an essential negative regulator of pathological cardiac hypertrophy

    Science.gov (United States)

    Deng, Ke-Qiong; Wang, Aibing; Ji, Yan-Xiao; Zhang, Xiao-Jing; Fang, Jing; Zhang, Yan; Zhang, Peng; Jiang, Xi; Gao, Lu; Zhu, Xue-Yong; Zhao, Yichao; Gao, Lingchen; Yang, Qinglin; Zhu, Xue-Hai; Wei, Xiang; Pu, Jun; Li, Hongliang

    2016-01-01

    Although pathological cardiac hypertrophy represents a leading cause of morbidity and mortality worldwide, our understanding of the molecular mechanisms underlying this disease is still poor. Here, we demonstrate that suppressor of IKKɛ (SIKE), a negative regulator of the interferon pathway, attenuates pathological cardiac hypertrophy in rodents and non-human primates in a TANK-binding kinase 1 (TBK1)/AKT-dependent manner. Sike-deficient mice develop cardiac hypertrophy and heart failure, whereas Sike-overexpressing transgenic (Sike-TG) mice are protected from hypertrophic stimuli. Mechanistically, SIKE directly interacts with TBK1 to inhibit the TBK1-AKT signalling pathway, thereby achieving its anti-hypertrophic action. The suppression of cardiac remodelling by SIKE is further validated in rats and monkeys. Collectively, these findings identify SIKE as a negative regulator of cardiac remodelling in multiple animal species due to its inhibitory regulation of the TBK1/AKT axis, suggesting that SIKE may represent a therapeutic target for the treatment of cardiac hypertrophy and heart failure. PMID:27249321

  16. Kruppel-like factor 2 is required for normal mouse cardiac development.

    Directory of Open Access Journals (Sweden)

    Aditi R Chiplunkar

    Full Text Available Krüppel-like factor 2 (KLF2 is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5 in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By E10.5, traditional and endothelial-specific FVB/N KLF2-/- AV cushions are hypocellular, suggesting that the cells accumulating at the AV canal have a defect in endothelial to mesenchymal transformation (EMT. E10.5 FVB/N KLF2-/- hearts have reduced glycosaminoglycans in the cardiac jelly, correlating with the reduced EMT. However, the number of mesenchymal cells migrating from FVB/N KLF2-/- AV explants into a collagen matrix is reduced considerably compared to wild-type, suggesting that the EMT defect is not due solely to abnormal cardiac jelly. Echocardiography of E10.5 FVB/N KLF2-/- embryos indicates that they have abnormal heart function compared to wild-type. E10.5 C57BL/6 KLF2-/- hearts have largely normal AV cushions. However, E10.5 FVB/N and C57BL/6 KLF2-/- embryos have a delay in the formation of the atrial septum that is not observed in a defined mixed background. KLF2 ablation results in reduced Sox9, UDP-glucose dehydrogenase (Ugdh, Gata4 and Tbx5 mRNA in FVB/N AV canals. KLF2 binds to the Gata4, Tbx5 and Ugdh promoters in chromatin immunoprecipitation assays, indicating that KLF2 could directly regulate these genes. In conclusion, KLF2-/- heart phenotypes are genetic background-dependent. KLF2 plays a role in EMT through its regulation of important cardiovascular genes.

  17. Cardiac troponin T is necessary for normal development in the embryonic chick heart.

    Science.gov (United States)

    England, Jennifer; Pang, Kar Lai; Parnall, Matthew; Haig, Maria Isabel; Loughna, Siobhan

    2016-09-01

    The heart is the first functioning organ to develop during embryogenesis. The formation of the heart is a tightly regulated and complex process, and alterations to its development can result in congenital heart defects. Mutations in sarcomeric proteins, such as alpha myosin heavy chain and cardiac alpha actin, have now been associated with congenital heart defects in humans, often with atrial septal defects. However, cardiac troponin T (cTNT encoded by gene TNNT2) has not. Using gene-specific antisense oligonucleotides, we have investigated the role of cTNT in chick cardiogenesis. TNNT2 is expressed throughout heart development and in the postnatal heart. TNNT2-morpholino treatment resulted in abnormal atrial septal growth and a reduction in the number of trabeculae in the developing primitive ventricular chamber. External analysis revealed the development of diverticula from the ventricular myocardial wall which showed no evidence of fibrosis and still retained a myocardial phenotype. Sarcomeric assembly appeared normal in these treated hearts. In humans, congenital ventricular diverticulum is a rare condition, which has not yet been genetically associated. However, abnormal haemodynamics is known to cause structural defects in the heart. Further, structural defects, including atrial septal defects and congenital diverticula, have previously been associated with conduction anomalies. Therefore, to provide mechanistic insights into the effect that cTNT knockdown has on the developing heart, quantitative PCR was performed to determine the expression of the shear stress responsive gene NOS3 and the conduction gene TBX3. Both genes were differentially expressed compared to controls. Therefore, a reduction in cTNT in the developing heart results in abnormal atrial septal formation and aberrant ventricular morphogenesis. We hypothesize that alterations to the haemodynamics, indicated by differential NOS3 expression, causes these abnormalities in growth in cTNT knockdown

  18. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  19. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. PMID:26718971

  20. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 1D Simulation Study

    OpenAIRE

    Gómez García, Juan Francisco; Romero Pérez, Lucia; Ferrero De Loma-Osorio, José María; Trenor Gomis, Beatriz Ana

    2014-01-01

    Background: Heart failure is a final common pathway or descriptor for various cardiac pathologies. It is associated with sudden cardiac death, which is frequently caused by ventricular arrhythmias. Electrophysiological remodeling, intercellular uncoupling, fibrosis and autonomic imbalance have been identified as major arrhythmogenic factors in heart failure etiology and progression. Objective: In this study we investigate in silico the role of electrophysiological and structur...

  1. Development of a theoretical guide for nursing care in cardiac arrest

    Directory of Open Access Journals (Sweden)

    Aliandra Bittencourt da Silva

    2013-11-01

    Full Text Available This study aimed to identify the knowledge on cardiorespiratory arrest among nurses in a hospital of Vale do Paraíba, São Paulo, Brazil, and develop a theoretical guide for care of this emergency. We prepared an instrument of data collection based on relevant literature and the 2010 AHA Guidelines for CPR, from August to October 2012. The sample consisted of 41 nurses who deliver care activities in various units of the hospital. The study showed that professional participants said they were able to act in cardiopulmonary resuscitation, however, there were limitations of knowledge about the theme. Given the above, we developed a theoretical guide for cardiac arrest care based on scientific literature and covering questions submitted by nurses.

  2. Cardiac biomarkers in children with congenital heart disease

    Institute of Scientific and Technical Information of China (English)

    Masaya Sugimoto; Seiko Kuwata; Clara Kurishima; Jeong Hye Kim; Yoich Iwamoto; Hideaki Senzaki

    2015-01-01

    Background: Most congenital heart diseases (CHDs) have specific hemodynamics, including volume and pressure overload, as well as cyanosis and pulmonary hypertension, associated with anatomical abnormalities. Such hemodynamic abnormalities can cause activation of neurohormones, inflammatory cytokines, fibroblasts, and vascular endothelial cells, which in turn contribute to the development of pathologic conditions such as cardiac hypertrophy,fi brosis, and cardiac cell damages and death. Measuring biomarker levels facilitates the prediction of these pathological changes, and provides information about the stress placed on the myocardial cells, the severity of the damage, the responses of neurohumoral factors, and the remodeling of the ventricle. Compared to the ample information on cardiac biomarkers in adult heart diseases, data from children with CHD are still limited. Data sources: We reviewed cardiac biomarkers-specifi cally focusing on troponin as a biomarker of myocardial damage, amino-terminal procollagen type III peptide (PIIIP) as a biomarker of myocardialfi brosis and stromal remodeling, and B-type natriuretic peptide (BNP)/N-terminal proBNP as biomarkers of cardiac load and heart failure, by introducing relevant publications, including our own, on pediatric CHD patients as well as adults. Results: Levels of highly sensitive troponin I are elevated in patients with atrial septal defects (ASDs) and ventricular septal defects (VSDs). PIIIP levels are also elevated in patients with ASD, VSD, pulmonary stenosis, and Tetralogy of Fallot. Measurement of BNP and N-terminal proBNP levels shows good correlation with heart failure score in children. Conclusions: In the treatment of children with CHD requiring delicate care, it is vital to know the specifi c degree of myocardial damage and severity of heart failure. Cardiac biomarkers are useful tools for ascertaining the condition of CHDs with ease and are likely to be useful in determining the appropriate care of

  3. Electrophysiological and structural remodeling in heart failure modulate arrhythmogenesis. 2D simulation study.

    Directory of Open Access Journals (Sweden)

    Juan F Gomez

    Full Text Available Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure.In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiological and anatomical remodeling using computer simulations.The electrical activity of human transmural ventricular tissue (5 cm × 5 cm was simulated using the human ventricular action potential model Grandi et al. under control and heart failure conditions. The MacCannell et al. model was used to model fibroblast electrical activity, and their electrotonic interactions with myocytes. Selected degrees of diffuse fibrosis and variations in intercellular coupling were considered and the vulnerable window (VW for reentry was evaluated following cross-field stimulation.No reentry was observed in normal conditions or in the presence of HF ionic remodeling. However, defined amount of fibrosis and/or cellular uncoupling were sufficient to elicit reentrant activity. Under conditions where reentry was generated, HF electrophysiological remodeling did not alter the width of the VW. However, intermediate fibrosis and cellular uncoupling significantly widened the VW. In addition, biphasic behavior was observed, as very high fibrotic content or very low tissue conductivity hampered the development of reentry. Detailed phase analysis of reentry dynamics revealed an increase of phase singularities with progressive fibrotic components.Structural remodeling is a key factor in the genesis of vulnerability to reentry. A range of intermediate levels of fibrosis and intercellular uncoupling can combine to favor reentrant activity.

  4. Neural remodeling in retinal degeneration.

    Science.gov (United States)

    Marc, Robert E; Jones, Bryan W; Watt, Carl B; Strettoi, Enrica

    2003-09-01

    Mammalian retinal degenerations initiated by gene defects in rods, cones or the retinal pigmented epithelium (RPE) often trigger loss of the sensory retina, effectively leaving the neural retina deafferented. The neural retina responds to this challenge by remodeling, first by subtle changes in neuronal structure and later by large-scale reorganization. Retinal degenerations in the mammalian retina generally progress through three phases. Phase 1 initiates with expression of a primary insult, followed by phase 2 photoreceptor death that ablates the sensory retina via initial photoreceptor stress, phenotype deconstruction, irreversible stress and cell death, including bystander effects or loss of trophic support. The loss of cones heralds phase 3: a protracted period of global remodeling of the remnant neural retina. Remodeling resembles the responses of many CNS assemblies to deafferentation or trauma, and includes neuronal cell death, neuronal and glial migration, elaboration of new neurites and synapses, rewiring of retinal circuits, glial hypertrophy and the evolution of a fibrotic glial seal that isolates the remnant neural retina from the surviving RPE and choroid. In early phase 2, stressed photoreceptors sprout anomalous neurites that often reach the inner plexiform and ganglion cell layers. As death of rods and cones progresses, bipolar and horizontal cells are deafferented and retract most of their dendrites. Horizontal cells develop anomalous axonal processes and dendritic stalks that enter the inner plexiform layer. Dendrite truncation in rod bipolar cells is accompanied by revision of their macromolecular phenotype, including the loss of functioning mGluR6 transduction. After ablation of the sensory retina, Müller cells increase intermediate filament synthesis, forming a dense fibrotic layer in the remnant subretinal space. This layer invests the remnant retina and seals it from access via the choroidal route. Evidence of bipolar cell death begins in

  5. Cardiac Pacemakers

    International Nuclear Information System (INIS)

    A complete survey of physiological biophysical,clinical and engineering aspects of cardiac facing,including the history and an assessment of possible future developments.Among the topics studied are: pacemakers, energy search, heart stimulating with pacemakers ,mathematical aspects of the electric cardio stimulation chronic, pacemaker implants,proceeding,treatment and control

  6. Diagnostic tools assessing airway remodelling in asthma.

    Science.gov (United States)

    Manso, L; Reche, M; Padial, M A; Valbuena, T; Pascual, C

    2012-01-01

    Asthma is an inflammatory disease of the lower airways characterised by the presence of airway inflammation, reversible airflow obstruction and airway hyperresponsiveness and alterations on the normal structure of the airways, known as remodelling. Remodelling is characterised by the presence of metaplasia of mucous glands, thickening of the lamina reticularis, increased angiogenesis, subepithelial fibrosis and smooth muscle hypertrophy/hyperplasia. Several techniques are being optimised at present to achieve a suitable diagnosis for remodelling. Diagnostic tools could be divided into two groups, namely invasive and non-invasive methods. Invasive techniques bring us information about bronchial structural alterations, obtaining this information directly from pathological tissue, and permit measure histological modification placed in bronchi layers as well as inflammatory and fibrotic cell infiltration. Non-invasive techniques were developed to reduce invasive methods disadvantages and measure airway remodelling-related markers such as cytokines, inflammatory mediators and others. An exhaustive review of diagnostic tools used to analyse airway remodelling in asthma, including the most useful and usually employed methods, as well as the principal advantages and disadvantages of each of them, bring us concrete and summarised information about all techniques used to evaluate alterations on the structure of the airways. A deep knowledge of these diagnostic tools will make an early diagnosis of airway remodelling possible and, probably, early diagnosis will play an important role in the near future of asthma. PMID:22236733

  7. Walking with Gianluca Di Bella during the development of clinical cardiac imaging

    OpenAIRE

    2010-01-01

    Cardiac magnetic resonance imaging (MRI) for the diagnosis and management of many cardiac diseases has been established in clinical practice. It provides anatomic and functional information and is the most precise technique for quantification of ventricular volume, function and mass. Among cardiac MRI sequences used in clinical practice, delayed contrast enhancement is an accurate and reliable method used in the diagnosis of ischemic and nonischemic cardiomyopathies. In addition, new technolo...

  8. Design, development, and evaluation of focused ultrasound arrays for transesophageal cardiac ablations

    Science.gov (United States)

    Lee, Hotaik

    The ultimate purpose of this dissertation is the evaluation of the feasibility of transesophageal cardiac surgery in arrhythmia treatment, using therapeutic ultrasound energy without the requirement for surgical incisions or blood contact. Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting over 2.2 million Americans. One effective treatment is cardiac ablation, which shows a high rate of success in treating paroxysmal AF. As a prevailing modality for this treatment, catheter ablation using radiofrequency has been effective, but there is measurable morbidity and significant costs and time associated with this invasive procedure for permanent or persistent AF. To address these issues, a transesophageal ultrasound applicator for noninvasive cardiac ablations has been designed, developed and evaluated in this dissertation. Focused ultrasound for thermal ablation has gained interest for decades due to its noninvasive characteristics. Since the esophagus is close to the posterior of the left atrium, its position makes it attractive for the incision-less surgery of the selected area of the heart using ultrasound. The overall goal of this study is to bring an applicator as closely as possible to the heart in order to effectively deliver ultrasound energy, and create electrically isolating lesions in myocardial tissue, replicating the currently used Maze procedure. The Maze procedure is a surgical operation that treats AF by creating a grid of incisions resulting in non-conductive scar tissue in the atria. The initial design of an ultrasound applicator capable of creating atrial lesions from the esophagus, involved evaluating sound pressure fields within layers of the esophagus and myocardium. Based on the multiple factors of the simulation results of transducer arrays, current transesophageal medical devices, and the throat anatomy, a focused ultrasound transducer that can be inserted into the esophagus has been designed and tested. In this study, a

  9. Balancing radiation risks and benefits of cardiac imaging: challenges for developed countries

    International Nuclear Information System (INIS)

    Full text: Cardiovascular disease remains the leading cause of death in the US, EU, Canada, Australia, and New Zealand, although coronary disease mortality has decreased due to improvements in prevention, diagnosis, and treatment. In many developed countries, most cardiologists now perform procedures involving radiopharmaceuticals, CT, or fluoroscopy. Their increased utilization, while contributing to improved care for patients with known or suspected heart disease, has been accompanied by a sharp increase in collective doses from medical radiation. E.g., an estimated ∼ 10% (∼ 0.6 mSv/person/y) of the collective dose to the US population is now attributed to nuclear stress tests. Radiation risk from any modality is highly dependent on patient age and gender. Cardiologists, like most non-radiologists, have had limited training in the safe use of radiation and are generally unaware of such facts. While one encouraging sign has been the development of appropriateness criteria for various cardiac imaging modalities, much work remains to advance radiological protection for the tens of millions of patients each year who receive cardiac imaging studies. Here we address current efforts to balance benefits of cardiac imaging with radiation risks, dose-reduction strategies, and future desiderata. General themes are improvements in technology, education, clinical standards, and reimbursement policies for these examinations. The vast majority of nuclear cardiology studies are performed using SPECT, and the radiopharmaceuticals used most widely are 99mTc sestamibi and tetrofosmin, and 201Tl. Effective doses are considerably higher for standard injected activities of 201Tl than for 99mTc agents, and the highest doses, ∼ 24 mSv, are associated with dual isotope (rest 201Tl, stress 99mTc) protocols. E.g., in the US, 1/4 of nuclear stress tests are still performed using dual isotope protocols, a practice fostered by current structuring of reimbursement. Although most stress

  10. Development and clinical study of mobile 12-lead electrocardiography based on cloud computing for cardiac emergency.

    Science.gov (United States)

    Fujita, Hideo; Uchimura, Yuji; Waki, Kayo; Omae, Koji; Takeuchi, Ichiro; Ohe, Kazuhiko

    2013-01-01

    To improve emergency services for accurate diagnosis of cardiac emergency, we developed a low-cost new mobile electrocardiography system "Cloud Cardiology®" based upon cloud computing for prehospital diagnosis. This comprises a compact 12-lead ECG unit equipped with Bluetooth and Android Smartphone with an application for transmission. Cloud server enables us to share ECG simultaneously inside and outside the hospital. We evaluated the clinical effectiveness by conducting a clinical trial with historical comparison to evaluate this system in a rapid response car in the real emergency service settings. We found that this system has an ability to shorten the onset to balloon time of patients with acute myocardial infarction, resulting in better clinical outcome. Here we propose that cloud-computing based simultaneous data sharing could be powerful solution for emergency service for cardiology, along with its significant clinical outcome. PMID:23920851

  11. Changes in the microvascular network during cardiac growth, development, and aging.

    Science.gov (United States)

    Rakusan, K; Cicutti, N; Flanagan, M F

    1994-01-01

    Quantitative changes in the terminal vascular bed of the mammalian heart were assessed during postnatal development and aging. The most striking feature is a considerable formation of new capillaries in the early postnatal period, accompanied by a moderate formation of new arterioles. On the other hand, coronary arterioles seem to disappear at a higher rate than capillaries in the senescent heart. We proposed a three-dimensional structural model of tissue capillary supply, defined as capillary domain area times capillary segment length. This so called capillary supply unit increases as a function of age and body growth. It is very similar in size and shape (length to width ratio) to cardiac myocytes. PMID:7849763

  12. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Directory of Open Access Journals (Sweden)

    Andoni Lancha

    Full Text Available Osteopontin (OPN is a multifunctional extracellular matrix (ECM protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT and liver in wild type (WT mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  13. Right and left ventricular cardiac function in a developed world population with human immunodeficiency virus studied with radionuclide ventriculography

    DEFF Research Database (Denmark)

    Lebech, Anne-Mette; Gerstoft, Jan; Hesse, Birger; Petersen, Claus Leth; Kjaer, Andreas

    2004-01-01

    -associated morbidity and mortality rates. Accordingly, the prevalence of HIV-associated cardiac dysfunction may also have changed. The aim of the study was to establish the prevalence of right- and left-sided cardiac dysfunction in a Danish HIV population, most of whom were undergoing HAART, with radionuclide...... endothelin-1 (ET-1) were measured. Thirty age- and sex-matched healthy volunteer subjects were included to establish reference values of radionuclide measurements of left and right ventricular ejection fraction and of left ventricular volume. RESULTS: Of 95 patients with HIV, 1 (1%) had a reduced left....... No correlations were found between reduced cardiac function and levels of the 3 peptides measured. CONCLUSIONS: No major dysfunction of the left ventricle is present in a developed world HIV population. However, a small but significant part of this population has modestly reduced right-sided systolic...

  14. The development of a new cardiac auscultation test: How do screening and diagnostic skills differ?

    DEFF Research Database (Denmark)

    Nielsen, Tommy; Mølgaard, Henning; Ringsted, Charlotte Vibeke;

    2010-01-01

    BACKGROUND: Newly qualified doctors are expected to be able to conduct a cardiac auscultation unassisted, but studies show conflicting results regarding cardiac auscultation skills. METHODS: A two-part test instrument was designed containing innovative recordings of heart sounds from patients...

  15. Cardiomyopathy induced by artificial cardiac pacing: myth or reality sustained by evidence?

    Directory of Open Access Journals (Sweden)

    Andrés Di Leoni Ferrari

    2014-09-01

    Full Text Available Implantable cardiac pacing systems are a safe and effective treatment for symptomatic irreversible bradycardia. Under the proper indications, cardiac pacing might bring significant clinical benefit. Evidences from literature state that the action of the artificial pacing system, mainly when the ventricular lead is located at the apex of the right ventricle, produces negative effects to cardiac structure (remodeling, dilatation and function (dissinchrony. Patients with previously compromised left ventricular function would benefit the least with conventional right ventricle apical pacing, and are exposed to the risk of developing higher incidence of morbidity and mortality for heart failure. However, after almost 6 decades of cardiac pacing, just a reduced portion of patients in general would develop these alterations. In this context, there are not completely clear some issues related to cardiac pacing and the development of this cardiomyopathy. Causality relationships among QRS widening with a left bundle branch block morphology, contractility alterations within the left ventricle, and certain substrates or clinical (previous systolic dysfunction, structural heart disease, time from implant or electrical conditions (QRS duration, percentage of ventricular stimulation are still subjecte of debate. This review analyses contemporary data regarding this new entity, and discusses alternatives of how to use cardiac pacing in this context, emphasizing cardiac resynchronization therapy.

  16. Association between cardiac biomarkers and the development of ESRD in patients with type 2 diabetes mellitus, anemia, and CKD

    DEFF Research Database (Denmark)

    Desai, Akshay S; Toto, Robert; Jarolim, Petr;

    2011-01-01

    In patients with chronic kidney disease (CKD), as in other populations, elevations in cardiac biomarker levels predict increased risk of cardiovascular events. We examined the value of troponin T (TnT) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in assessing the risk of developing e...

  17. A mHealth cardiac rehabilitation exercise intervention: findings from content development studies

    Directory of Open Access Journals (Sweden)

    Pfaeffli Leila

    2012-05-01

    Full Text Available Abstract Background Involving stakeholders and consumers throughout the content and study design ensures interventions are engaging and relevant for end-users. The aim of this paper is to present the content development process for a mHealth (mobile phone and internet-based cardiac rehabilitation (CR exercise intervention. Methods An innovative mHealth intervention was developed with patient input using the following steps: conceptualization, formative research, pre-testing, and pilot testing. Conceptualization, including theoretical and technical aspects, was undertaken by experts. For the formative component, focus groups and interviews with cardiac patients were conducted to discuss their perceptions of a mHealth CR program. A general inductive thematic approach identified common themes. A preliminary library of text and video messages were then developed. Participants were recruited from CR education sessions to pre-test and provide feedback on the content using an online survey. Common responses were extracted and compiled. An iterative process was used to refine content prior to pilot testing and conduct of a randomized controlled trial. Results 38 CR patients and 3 CR nurses participated in the formative research and 20 CR patients participated in the content pre-testing. Participants perceived the mHealth program as an effective approach to inform and motivate patients to exercise. For the qualitative study, 100% (n = 41 of participants thought it to be a good idea, and 11% of participants felt it might not be useful for them, but would be for others. Of the 20 participants who completed the online survey, 17 out of 20 (85% stated they would sign up to a program where they could receive information by video messages on a website, and 12 out of 20 (60% showed interest in a texting program. Some older CR patients viewed technology as a potential barrier as they were unfamiliar with text messaging or did not have mobile phones. Steps to

  18. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult.

    Directory of Open Access Journals (Sweden)

    Vinicius S Carreira

    Full Text Available The Developmental Origins of Health and Disease (DOHaD Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR, either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease.

  19. Anti‐Remodeling and Anti‐Fibrotic Effects of the Neuregulin‐1β Glial Growth Factor 2 in a Large Animal Model of Heart Failure

    Science.gov (United States)

    Galindo, Cristi L.; Kasasbeh, Ehab; Murphy, Abigail; Ryzhov, Sergey; Lenihan, Sean; Ahmad, Farhaan A.; Williams, Philip; Nunnally, Amy; Adcock, Jamie; Song, Yanna; Harrell, Frank E.; Tran, Truc‐Linh; Parry, Tom J.; Iaci, Jen; Ganguly, Anindita; Feoktistov, Igor; Stephenson, Matthew K.; Caggiano, Anthony O.; Sawyer, Douglas B.; Cleator, John H.

    2014-01-01

    Background Neuregulin‐1β (NRG‐1β) is a growth factor critical for cardiac development and repair with therapeutic potential for heart failure. We previously showed that the glial growth factor 2 (GGF2) isoform of NRG‐1β improves cardiac function in rodents after myocardial infarction (MI), but its efficacy in a large animal model of cardiac injury has not been examined. We therefore sought to examine the effects of GGF2 on ventricular remodeling, cardiac function, and global transcription in post‐MI swine, as well as potential mechanisms for anti‐remodeling effects. Methods and Results MI was induced in anesthetized swine (n=23) by intracoronary balloon occlusion. At 1 week post‐MI, survivors (n=13) received GGF2 treatment (intravenous, biweekly for 4 weeks; n=8) or were untreated (n=5). At 5 weeks post‐MI, fractional shortening was higher (32.8% versus 25.3%, P=0.019), and left ventricular (LV) end‐diastolic dimension lower (4.5 versus 5.3 cm, P=0.003) in GGF2‐treated animals. Treatment altered expression of 528 genes, as measured by microarrays, including collagens, basal lamina components, and matricellular proteins. GGF2‐treated pigs exhibited improvements in LV cardiomyocyte mitochondria and intercalated disk structures and showed less fibrosis, altered matrix structure, and fewer myofibroblasts (myoFbs), based on trichrome staining, electron microscopy, and immunostaining. In vitro experiments with isolated murine and rat cardiac fibroblasts demonstrate that NRG‐1β reduces myoFbs, and suppresses TGFβ‐induced phospho‐SMAD3 as well as αSMA expression. Conclusions These results suggest that GGF2/NRG‐1β prevents adverse remodeling after injury in part via anti‐fibrotic effects in the heart. PMID:25341890

  20. Overexpression of junctophilin-2 does not enhance baseline function but attenuates heart failure development after cardiac stress.

    Science.gov (United States)

    Guo, Ang; Zhang, Xiaoying; Iyer, Venkat Ramesh; Chen, Biyi; Zhang, Caimei; Kutschke, William J; Weiss, Robert M; Franzini-Armstrong, Clara; Song, Long-Sheng

    2014-08-19

    Heart failure is accompanied by a loss of the orderly disposition of transverse (T)-tubules and a decrease of their associations with the junctional sarcoplasmic reticulum (jSR). Junctophilin-2 (JP2) is a structural protein responsible for jSR/T-tubule docking. Animal models of cardiac stresses demonstrate that down-regulation of JP2 contributes to T-tubule disorganization, loss of excitation-contraction coupling, and heart failure development. Our objective was to determine whether JP2 overexpression attenuates stress-induced T-tubule disorganization and protects against heart failure progression. We therefore generated transgenic mice with cardiac-specific JP2 overexpression (JP2-OE). Baseline cardiac function and Ca(2+) handling properties were similar between JP2-OE and control mice. However, JP2-OE mice displayed a significant increase in the junctional coupling area between T-tubules and the SR and an elevated expression of the Na(+)/Ca(2+) exchanger, although other excitation-contraction coupling protein levels were not significantly changed. Despite similar cardiac function at baseline, overexpression of JP2 provided significantly protective benefits after pressure overload. This was accompanied by a decreased percentage of surviving mice that developed heart failure, as well as preservation of T-tubule network integrity in both the left and right ventricles. Taken together, these data suggest that strategies to maintain JP2 levels can prevent the progression from hypertrophy to heart failure. PMID:25092313

  1. A novel approach for assessing cardiac fibrosis using label-free second harmonic generation.

    Science.gov (United States)

    Martin, Tamara P; Norris, Greg; McConnell, Gail; Currie, Susan

    2013-12-01

    To determine whether second harmonic generation (SHG) can be used as a novel and improved label-free technique for detection of collagen deposition in the heart. To verify whether SHG will allow accurate quantification of altered collagen deposition in diseased hearts following hypertrophic remodelling. Minimally invasive transverse aortic banding (MTAB) of mouse hearts was used to generate a reproducible model of cardiac hypertrophy. Physiological and functional assessment of hypertrophic development was performed using echocardiography and post-mortem analysis of remodelled hearts. Cardiac fibroblasts were isolated from sham-operated and hypertrophied hearts and proliferation rates compared. Multi-photon laser scanning microscopy was used to capture both two-photon excited autofluorescence (TPEF) and SHG images simultaneously in two channels. TPEF images were subtracted from SHG images and the resulting signal intensities from ventricular tissue sections were calculated. Traditional picrosirius red staining was used to verify the suitability of the SHG application. MTAB surgery induced significant hypertrophic remodelling and increased cardiac fibroblast proliferation. A significant increase in the density of collagen fibres between hypertrophic and control tissues (p < 0.05) was evident using SHG. Similar increases and patterns of staining were observed using parallel traditional picrosirius red staining of collagen. Label-free SHG microscopy provides a new alternative method for quantifying collagen deposition in fibrotic hearts. PMID:23921804

  2. Development and Implementation of Discrete Polymeric Microstructural Cues for Applications in Cardiac Tissue Engineering

    Science.gov (United States)

    Pinney, James Richardson

    Chronic fibrosis caused by acute myocardial infarction (MI) leads to increased morbidity and mortality due to cardiac dysfunction. Despite care in the acute setting of MI, subsequent development of scar tissue and a lack of treatments for this maladaptive response lead to a poor prognosis. This has increased burdens on the cost of healthcare due to chronic disability. Here a novel therapeutic strategy that aims to mitigate myocardial fibrosis by utilizing injectable polymeric microstructural cues to attenuate the fibrotic response and improve functional outcomes is presented. Additionally, applications of integrated chemical functionalizations into discrete, micro-scale polymer structures are discussed in the realm of tissue engineering in order to impart enhancements in in vivo localization, three-dimensional manipulation and drug delivery. Polymeric microstructures, termed "microrods" and "microcubes", were fabricated using photolithographic techniques and studied in three-dimensional culture models of the fibrotic environment and by direct injection into the infarct zone of adult Sprague-Dawley rats. In vitro gene expression and functional and histological results were analyzed, showing a dose-dependent down-regulation fibrotic indicators and improvement in cardiac function. Furthermore, iron oxide nanoparticles and functionalized fluorocarbons were incorporated into the polymeric microdevices to promote in situ visualization by magnetic resonance imaging as well as to facilitate the manipulation and alignment of microstructural cues in a tissue-realistic environment. Lastly, successful encapsulation of native MGF peptide within microrods is demonstrated with release over two weeks as a proof of concept in the ability to locally deliver myogenic or supportive pharmacotherapeutics to the injured myocardium. This work demonstrates the efficacy and versatility of discrete microtopographical cues to attenuate the fibrotic response after MI and suggests a novel

  3. 二尖瓣环位移对肥厚性重构患者左室收缩功能的评估作用%Evaluation of left ventricular systolic dysfunction by mitral annular displacement in patients with cardiac hypertrophy and remodeling

    Institute of Scientific and Technical Information of China (English)

    吴卫华; 黄艳; 陆静; 马兰; 魏松霞; 谢晓奕; 刘奇志; 王雷; 杨玲

    2011-01-01

    目的 应用超声二维斑点追踪显像技术测定二尖瓣环位移(MAD),探讨其在评估肥厚性重构所致的早期左室收缩功能减退方面的临床应用价值.方法 选择86例左室射血分数(LVEF)正常(>50%)的各类心肌肥厚(左室壁厚度≥12 mm)患者作为研究对象.采用Philips Sonos iE33超声仪进行检查,先通过M型超声计算出相对室壁厚度(RWT),然后取心尖四腔观分别采集二维和实时三维全容积(RT3D)图像.应用QLAB 6.2在机量化分析软件分别获取MAD相关参数(包括二尖瓣环中点位移和左室长轴缩短率)和经RT3D图像测得左室射血分数(RT3D-LVEF);计算三维心肌重构指标,包括左室舒末容积指数(LVEDVI)和左室质量指数(LVMI).将心肌肥厚患者中RWT<0.45且LVMI在正常范围内的患者归入肥厚正常几何构型组(HNG组),其余归入肥厚重构组(HR组);以46名年龄相匹配的健康志愿者作为正常对照组.结果 HNG组、HR组和正常对照组的RT3D-LVEF均在正常范围内,两两比较差异均无统计学意义(P>0.05).HR组的MAD各值和LVEDVI均显著低于HNG组和正常对照组,差异均有统计学意义(P<0.01或P<0.05);HNG组与正常对照组MAD相关参数值和LVEDVI比较差异均无统计学意义(P>0.05).Bland-Altman分析显示MAD各值的可重复性较高.结论 在心肌肥厚性重构患者中,与LVEF比较,MAD能更早地反映患者的左室收缩功能减退情况.%Objective To investigate the value of mitral annular displacement (MAD) by two-dimensional speckle tracking in evaluating left ventricular systolic dysfunction in patients with cardiac hypertrophy and remodeling.Methods Eightysix patients with cardiac hypertrophy ( left ventricular wall thickness ≥ 12 mm) and normal left ventricular ejection fraction (LVEF) ( > 50% ) were selected.Philips Sonos iE33 ultrasound device was used for examinations.Relative wall thickness (IRWT) was calculated by M mode ultrasound, and two

  4. A fly's view of neuronal remodeling.

    Science.gov (United States)

    Yaniv, Shiri P; Schuldiner, Oren

    2016-09-01

    Developmental neuronal remodeling is a crucial step in sculpting the final and mature brain connectivity in both vertebrates and invertebrates. Remodeling includes degenerative events, such as neurite pruning, that may be followed by regeneration to form novel connections during normal development. Drosophila provides an excellent model to study both steps of remodeling since its nervous system undergoes massive and stereotypic remodeling during metamorphosis. Although pruning has been widely studied, our knowledge of the molecular and cellular mechanisms is far from complete. Our understanding of the processes underlying regrowth is even more fragmentary. In this review, we discuss recent progress by focusing on three groups of neurons that undergo stereotypic pruning and regrowth during metamorphosis, the mushroom body γ neurons, the dendritic arborization neurons and the crustacean cardioactive peptide peptidergic neurons. By comparing and contrasting the mechanisms involved in remodeling of these three neuronal types, we highlight the common themes and differences as well as raise key questions for future investigation in the field. WIREs Dev Biol 2016, 5:618-635. doi: 10.1002/wdev.241 For further resources related to this article, please visit the WIREs website. PMID:27351747

  5. Evolving Cardiac Conduction Phenotypes in Developing Zebrafish Larvae: Implications to Drug Sensitivity

    OpenAIRE

    Yu, Fei; Huang, Jie; Adlerz, Katrina; Jadvar, Hossein; Hamdan, Mohamed H.; Chi, Neil; Chen, Jau-Nian; Hsiai, Tzung K.

    2010-01-01

    Cardiac arrhythmias include problems with impulse formation and/or conduction abnormalities. Zebrafish (Danio rerio) is an emerging model system for studying the cardiac conduction system. However, real-time recording of the electrocardiogram remains a challenge. In the present study, we assessed the feasibility of recording electrical cardiogram (ECG) signals from the zebrafish larvae using the micropipette electrodes, and demonstrated the dynamic changes in ECG signals and their sensitivity...

  6. Restenosis and remodeling

    International Nuclear Information System (INIS)

    Percutaneous Transluminal Coronary Angioplasty (PTCA) remains limited by restenosis that occurs in 30 to 50% of patients with coronary artery disease. During the last decade, numerous agents have been used to prevent restenosis. Despite positive results in animal models, no pharmacological therapy has been found to significantly decrease the risk of restenosis in humans. These discrepancies between animal models and clinical situation were probably related to an incomplete understanding of the mechanism of restenosis. Neointimal thickening occurs in response to experimental arterial injury with a balloon catheter. Neointimal formation involves different steps: smooth muscle cell activation, proliferation and migration, and the production of extracellular matrix. The factors that control neointimal hyperplasia include growth factors humoral factors and mechanical factors. Arterial remodeling also plays a major role in the restenosis process. Studies performed in animal and human subjects have established the potentials for 'constrictive remodeling' to reduce the post-angioplasty vessel area, thereby indirectly narrowing the vessel lumen and thus contributing to restenosis. The reduction of restenosis rate in patients with intracoronary stent implantation has been attributed to the preventive effect of stent itself for this negative remodeling. In addition to these mechanism for restenosis, intraluminal or intra-plaque thrombus formation, reendothelialization and apoptosis theories have been introduced and confirmed at least in part

  7. EGFR-Ras-Raf Signaling in Epidermal Stem Cells: Roles in Hair Follicle Development, Regeneration, Tissue Remodeling and Epidermal Cancers

    OpenAIRE

    Manuela Baccarini; Christian Rupp; Eszter Doma

    2013-01-01

    The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research mainly focuses on its role in cutaneous tumor initiation and maintenance, much less is known about Ras signaling in the epidermal stem cells, which are the main targets of skin carcinogenesis. In this review,...

  8. Towards the Automated Analysis and Database Development of Defibrillator Data from Cardiac Arrest

    Directory of Open Access Journals (Sweden)

    Trygve Eftestøl

    2014-01-01

    Full Text Available Background. During resuscitation of cardiac arrest victims a variety of information in electronic format is recorded as part of the documentation of the patient care contact and in order to be provided for case review for quality improvement. Such review requires considerable effort and resources. There is also the problem of interobserver effects. Objective. We show that it is possible to efficiently analyze resuscitation episodes automatically using a minimal set of the available information. Methods and Results. A minimal set of variables is defined which describe therapeutic events (compression sequences and defibrillations and corresponding patient response events (annotated rhythm transitions. From this a state sequence representation of the resuscitation episode is constructed and an algorithm is developed for reasoning with this representation and extract review variables automatically. As a case study, the method is applied to the data abstraction process used in the King County EMS. The automatically generated variables are compared to the original ones with accuracies ≥90% for 18 variables and ≥85% for the remaining four variables. Conclusions. It is possible to use the information present in the CPR process data recorded by the AED along with rhythm and chest compression annotations to automate the episode review.

  9. Development of a scalable suspension culture for cardiac differentiation from human pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Vincent C. Chen

    2015-09-01

    Full Text Available To meet the need of a large quantity of hPSC-derived cardiomyocytes (CM for pre-clinical and clinical studies, a robust and scalable differentiation system for CM production is essential. With a human pluripotent stem cells (hPSC aggregate suspension culture system we established previously, we developed a matrix-free, scalable, and GMP-compliant process for directing hPSC differentiation to CM in suspension culture by modulating Wnt pathways with small molecules. By optimizing critical process parameters including: cell aggregate size, small molecule concentrations, induction timing, and agitation rate, we were able to consistently differentiate hPSCs to >90% CM purity with an average yield of 1.5 to 2 × 109 CM/L at scales up to 1 L spinner flasks. CM generated from the suspension culture displayed typical genetic, morphological, and electrophysiological cardiac cell characteristics. This suspension culture system allows seamless transition from hPSC expansion to CM differentiation in a continuous suspension culture. It not only provides a cost and labor effective scalable process for large scale CM production, but also provides a bioreactor prototype for automation of cell manufacturing, which will accelerate the advance of hPSC research towards therapeutic applications.

  10. Intra-coronary administration of soluble receptor for advanced glycation end-products attenuates cardiac remodeling with decreased myocardial transforming growth factor-β1 expression and fibrosis in minipigs with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    LU Lin; SHEN Wei-feng; ZHANG Qi; XU Yan; ZHU Zheng-bin; GENG Liang; WANG Ling-jie; JIN Cao; CHEN Qiu-jing; Ann Marie Schmidt

    2010-01-01

    Background The cardioprotective effects of soluble receptor for advanced glycation end-products (sRAGE) have not been evaluated in large animals and the underlying mechanisms are not fully understood. This study aimed to evaluate the effects of intra-coronary administration of sRAGE on left ventricular function and myocardial remodeling in a porcine model of ischemia-reperfusion (I/R) injury. Methods Ten male minipigs with I/R injury were randomly allocated to receive intra-coronary administration of sRAGE (sRAGE group, n=5) or saline (control group, n=5). Echocardiography was performed before and 2 months after infarction. Myocardial expression of transforming growth factor (TGF)-β1was determined by immunohistochemistry and fibrosis was evaluated by Sirius red staining. Results As compared with the baseline values in the control animals, left ventricular end-diastolic volume (from (19.5 5.1) to (32.3 5.6) ml, P <0.05) and end-systolic volume (from (8.3 3.2) to (15.2 4.1) ml, P <0.05) were significantly increased, whereas ejection fraction was decreased (from (61.6 13.3)% to (50.2 11.9)%, P<0.05). No obvious change in these parameters was observed in the sRAGE group. Myocardial expression of TGF-β1 was significantly elevated in the infarct and non-infarct regions in the control group, as compared with sRAGE group (both P<0.01). Fibrotic lesions were consistently more prominent in the infarct region of the myocardium in the control animals (P<0.05). Conclusion Intra-coronary sRAGE administration attenuates RAGE-mediated myocardial fibrosis and I/R injury through a TGF-β1-dependent mechanism, suggesting a clinical potential in treating RAGE/ligand-associated cardiovascular diseases.

  11. Biomechanical Remodeling of the Diabetic Gastrointestinal Tract

    DEFF Research Database (Denmark)

    Zhao, Jingbo; Liao, Donghua; Yang, Jian;

    2010-01-01

    several years, several studies demonstrated that experimental diabetes induces GI morphological and biomechanical remodeling. Following the development of diabetes, the GI wall becomes thicker and the stiffness of the GI wall increases in a time-dependent manner. It is well known that mechanosensitive...... the biomechanical environment of the mechanosensitive nerve endings, therefore, the structure as well as the tension, stress and strain distribution in the GI wall is important for the sensory and motor function. Biomechanical remodeling of diabetic GI tract including alterations of residual strain and increase...

  12. EGFR-Ras-Raf Signaling in Epidermal Stem Cells: Roles in Hair Follicle Development, Regeneration, Tissue Remodeling and Epidermal Cancers

    Directory of Open Access Journals (Sweden)

    Manuela Baccarini

    2013-09-01

    Full Text Available The mammalian skin is the largest organ of the body and its outermost layer, the epidermis, undergoes dynamic lifetime renewal through the activity of somatic stem cell populations. The EGFR-Ras-Raf pathway has a well-described role in skin development and tumor formation. While research mainly focuses on its role in cutaneous tumor initiation and maintenance, much less is known about Ras signaling in the epidermal stem cells, which are the main targets of skin carcinogenesis. In this review, we briefly discuss the properties of the epidermal stem cells and review the role of EGFR-Ras-Raf signaling in keratinocyte stem cells during homeostatic and pathological conditions.

  13. A case of Hodgkin`s disease presenting a cardiac tamponade during treatment developed a pancytopenia after cessation of chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Ohta, Shigeru; Iwami, Mika; Narita, Tsutomu; Higashino, Katsumi; Suzuki, Atsushi; Taga, Takashi; Shimada, Morimi [Shiga Univ. of Medical Science, Otsu (Japan)

    1998-10-01

    There had been many reports about cardiac complications of patients with Hodgkin`s disease (HD) after cessation of treatment in Europe and the United States. However, cases of HD accompanied with these complications were extremely rare in Japan. We report a case with HD that developed a cardiac tamponade during the clinical course of chemotherapy and showed a pancytopenia after cessation of chemotherapy. The case was a 14 year-old boy with HD (nodular sclerosis) of anterior upper mediastinum origin. He received modified MOPP therapy and irradiation to the semimantle field and to the mediastinum. The total dose of radiation was 36.3 Gy. He suddenly developed a chest pain, chest discomfort, and dyspnea during the sixth course of chemotherapy. He was diagnosed to have a cardiac tamponade by thoracentesis. The symptoms were improved by continuous transcutaneous drainage. The invasion of HD into the effusion was not detected by cytology, and the chemotherapy was completed after one course. However, he gradually developed a macrocytic anemia and finally developed a pancytopenia. The bone marrow specimen revealed a hypoplasia without evidence of pathological cells. The karyotype of marrow derived cells was normal. With oxymetholone administration, the pancytopenia has improved in four months. He has now been doing well for five years after the cessation of therapy. (author)

  14. Connexin Remodeling Contributes to Atrial Fibrillation

    OpenAIRE

    Michelle M Jennings; J Kevin Donahue

    2013-01-01

    Atrial fibrillation significantly contributes to mortality and morbidity through increased risk of stroke, heart failure and myocardial infarcts. Investigations of mechanisms responsible for the development and maintenance of atrial fibrillation have highlighted the importance of gap junctional remodeling. Connexins 40 and 43, the major atrial gap junctional proteins, undergo considerable alterations in expression and localization in atrial fibrillation, creating an environment conducive to s...

  15. 胰岛素对大鼠心肌梗死后心室重构和心脏功能的影响及其机制%Effects of insulin on ventricular remodeling and cardiac functions after myocardial infarction and its underlying mechanism

    Institute of Scientific and Technical Information of China (English)

    韦广洪; 付锋; 马斌; 薛洋; 李嘉; 张利华

    2013-01-01

    目的:探讨胰岛素对大鼠心肌梗死(MI)后心室重构和心脏功能的影响及其机制.方法:80只成年雄性Sprague-Dawley大鼠行冠状动脉左前降支(LAD)结扎制备MI模型,随机分为5组:即假手术(Sham)组(n=20)、生理盐水对照(MI+ NS)组(n=20)、胰岛素治疗(MI+ Ins)组(n=20)、肿瘤坏死因子α(TNF-α)拮抗剂益赛普治疗(MI+ En)组(n=10)及Ins+ En治疗(MI+ Ins+ En)组(n=10).用ELISA法检测各组大鼠在MI后1周和4周时,心肌及血清TNF-α的水平.超声心动图测定各组大鼠左室射血分数(EF)、缩短分数(FS)和左心室舒张末内径(LVEDD)、左心室收缩末内径(LVESD)、经右颈总动脉插管测定血压(BP)、左室舒张压(LVDP)和最大左室舒张压/收缩压变化速率(±LVdp/dtmax).结果:大鼠MI后心肌中TNF-α增加,Ins治疗可明显降低大鼠心肌中TNF-α的含量(P<0.05,n=6).Ins治疗组大鼠EF、FS、LVDP和±LVdp/dtmax均明显高于对照组(P <0.05,n=10),LVESD明显低于对照组(P<0.05,n=10).与单独En治疗组相比,Ins+ En治疗组大鼠EF、FS、LVDP和±LVdp/dtmax明显升高、LVESD明显降低(P <0.05,n=10).结论:Ins可抑制MI后心室的扩张,改善心脏功能,但其机制不依赖于抑制心肌TNF-α的产生.%AIM: To investigate the effect of insulin treatment on ventricular remodeling and cardiac functions after myocardial infarction (MI) and the underlying mechanism. METHODS: MI models were established by ligation of the left anterior descending coronary artery (LAD). Eighty male adult Sprague Dawley rats were randomly divided into five groups: sham (n = 20) , MI + saline ( n = 20) , MI + insulin (n = 20) , MI + etanercept ( n = 10) , and MI + etanercept + insulin ( n = 10 ) . Serum and myocardial tumor necrosis factor-α (TNF-α) were measured at 1 week and 4 weeks after MI. Left ventricular (LV) fractional shortening ( FS) , ejection fraction ( EF) , LV end-diastolic diameter ( LVEDD) and end-systolic diameter (LVESD) were measured

  16. HEART FAILURE WITH LOW CARDIAC OUTPUT AND RISK OF DEVELOPMENT OF LESIONS IN THE CEREBRAL WHITE MATTER

    OpenAIRE

    2005-01-01

    Aim: Diminished cardiac output can lead to the development of white matter lesions. White matter lesions are related to cognitive impairment, stroke risk and vascular death, yet the precise aetiology is uncertain. Methods: In this study we recruited 130 patients attending our medicine and neurology outpatient department, and divided them into those with a history of heart failure (n:24), atrial fibrillation (n:26), and those with atherosclerotic risk factors (n:80). The patients without low o...

  17. Recent developments in using mechanistic cardiac modelling for drug safety evaluation.

    Science.gov (United States)

    Davies, Mark R; Wang, Ken; Mirams, Gary R; Caruso, Antonello; Noble, Denis; Walz, Antje; Lavé, Thierry; Schuler, Franz; Singer, Thomas; Polonchuk, Liudmila

    2016-06-01

    On the tenth anniversary of two key International Conference on Harmonisation (ICH) guidelines relating to cardiac proarrhythmic safety, an initiative aims to consider the implementation of a new paradigm that combines in vitro and in silico technologies to improve risk assessment. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative (co-sponsored by the Cardiac Safety Research Consortium, Health and Environmental Sciences Institute, Safety Pharmacology Society and FDA) is a bold and welcome step in using computational tools for regulatory decision making. This review compares and contrasts the state-of-the-art tools from empirical to mechanistic models of cardiac electrophysiology, and how they can and should be used in combination with experimental tests for compound decision making. PMID:26891981

  18. Myocardial reverse remodeling: how far can we rewind?

    Science.gov (United States)

    Rodrigues, Patrícia G; Leite-Moreira, Adelino F; Falcão-Pires, Inês

    2016-06-01

    Heart failure (HF) is a systemic disease that can be divided into HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). HFpEF accounts for over 50% of all HF patients and is typically associated with high prevalence of several comorbidities, including hypertension, diabetes mellitus, pulmonary hypertension, obesity, and atrial fibrillation. Myocardial remodeling occurs both in HFrEF and HFpEF and it involves changes in cardiac structure, myocardial composition, and myocyte deformation and multiple biochemical and molecular alterations that impact heart function and its reserve capacity. Understanding the features of myocardial remodeling has become a major objective for limiting or reversing its progression, the latter known as reverse remodeling (RR). Research on HFrEF RR process is broader and has delivered effective therapeutic strategies, which have been employed for some decades. However, the RR process in HFpEF is less clear partly due to the lack of information on HFpEF pathophysiology and to the long list of failed standard HF therapeutics strategies in these patient's outcomes. Nevertheless, new proteins, protein-protein interactions, and signaling pathways are being explored as potential new targets for HFpEF remodeling and RR. Here, we review recent translational and clinical research in HFpEF myocardial remodeling to provide an overview on the most important features of RR, comparing HFpEF with HFrEF conditions. PMID:26993225

  19. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease

    Directory of Open Access Journals (Sweden)

    Mario Notari

    2015-01-01

    Full Text Available miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options.

  20. Update on the Pathogenic Implications and Clinical Potential of microRNAs in Cardiac Disease.

    Science.gov (United States)

    Notari, Mario; Pulecio, Julián; Raya, Ángel

    2015-01-01

    miRNAs, a unique class of endogenous noncoding RNAs, are highly conserved across species, repress gene translation upon binding to mRNA, and thereby influence many biological processes. As such, they have been recently recognized as regulators of virtually all aspects of cardiac biology, from the development and cell lineage specification of different cell populations within the heart to the survival of cardiomyocytes under stress conditions. Various miRNAs have been recently established as powerful mediators of distinctive aspects in many cardiac disorders. For instance, acute myocardial infarction induces cardiac tissue necrosis and apoptosis but also initiates a pathological remodelling response of the left ventricle that includes hypertrophic growth of cardiomyocytes and fibrotic deposition of extracellular matrix components. In this regard, recent findings place various miRNAs as unquestionable contributing factors in the pathogenesis of cardiac disorders, thus begging the question of whether miRNA modulation could become a novel strategy for clinical intervention. In the present review, we aim to expose the latest mechanistic concepts regarding miRNA function within the context of CVD and analyse the reported roles of specific miRNAs in the different stages of left ventricular remodelling as well as their potential use as a new class of disease-modifying clinical options. PMID:26221581

  1. The role of cardiac magnetic resonance imaging following acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Dennis T.L.; Richardson, James D.; Puri, Rishi; Nelson, Adam J.; Teo, Karen S.L.; Worthley, Matthew I. [Royal Adelaide Hospital, Cardiovascular Research Centre, Adelaide (Australia); University of Adelaide, Department of Medicine, Adelaide (Australia); Bertaso, Angela G. [Royal Adelaide Hospital, Cardiovascular Research Centre, Adelaide (Australia); Worthley, Stephen G. [Royal Adelaide Hospital, Cardiovascular Research Centre, Adelaide (Australia); University of Adelaide, Department of Medicine, Adelaide (Australia); Cardiovascular Investigational Unit, Adelaide, SA (Australia)

    2012-08-15

    Advances in the management of myocardial infarction have resulted in substantial reductions in morbidity and mortality. However, after acute treatment a number of diagnostic and prognostic questions often remain to be answered, whereby cardiac imaging plays an essential role. For example, some patients will sustain early mechanical complications after infarction, while others may develop significant ventricular dysfunction. Furthermore, many individuals harbour a significant burden of residual coronary disease for which clarification of functional ischaemic status and/or viability of the suspected myocardial territory is required. Cardiac magnetic resonance (CMR) imaging is well positioned to fulfil these requirements given its unparalleled capability in evaluating cardiac function, stress ischaemia testing and myocardial tissue characterisation. This review will focus on the utility of CMR in resolving diagnostic uncertainty, evaluating early complications following myocardial infarction, assessing inducible ischaemia, myocardial viability, ventricular remodelling and the emerging role of CMR-derived measures as endpoints in clinical trials. (orig.)

  2. Recipient–derived EDA fibronectin promotes cardiac allograft fibrosis

    Science.gov (United States)

    Booth, Adam J; Wood, Sherri C; Cornett, Ashley M; Dreffs, Alyssa A; Lu, Guanyi; Muro, Andrés F; White, Eric S; Bishop, D Keith

    2014-01-01

    Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long-term allograft survival. While initiating elements of anti-allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A-containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN-deficient (EDA−/−) and wild-type (WT) mice. While EDA−/− mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA−/− mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra-graft expression of pro-fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T-helper lineages. Conditions supporting regulatory T-cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient-derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft-protective, may drive production of ECM molecules which

  3. Longstanding hyperthyroidism is associated with normal or enhanced intrinsic cardiomyocyte function despite decline in global cardiac function.

    Directory of Open Access Journals (Sweden)

    Nathan Y Weltman

    Full Text Available Thyroid hormones (THs play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH. LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function.

  4. Fermitins, the orthologs of mammalian Kindlins, regulate the development of a functional cardiac syncytium in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    James H Catterson

    Full Text Available The vertebrate Kindlins are an evolutionarily conserved family of proteins critical for integrin signalling and cell adhesion. Kindlin-2 (KIND2 is associated with intercalated discs in mice, suggesting a role in cardiac syncytium development; however, deficiency of Kind2 leads to embryonic lethality. Morpholino knock-down of Kind2 in zebrafish has a pleiotropic effect on development that includes the heart. It therefore remains unclear whether cardiomyocyte Kind2 expression is required for cardiomyocyte junction formation and the development of normal cardiac function. To address this question, the expression of Fermitin 1 and Fermitin 2 (Fit1, Fit2, the two Drosophila orthologs of Kind2, was silenced in Drosophila cardiomyocytes. Heart development was assessed in adult flies by immunological methods and videomicroscopy. Silencing both Fit1 and Fit2 led to a severe cardiomyopathy characterised by the failure of cardiomyocytes to develop as a functional syncytium and loss of synchrony between cardiomyocytes. A null allele of Fit1 was generated but this had no impact on the heart. Similarly, the silencing of Fit2 failed to affect heart function. In contrast, the silencing of Fit2 in the cardiomyocytes of Fit1 null flies disrupted syncytium development, leading to severe cardiomyopathy. The data definitively demonstrate a role for Fermitins in the development of a functional cardiac syncytium in Drosophila. The findings also show that the Fermitins can functionally compensate for each other in order to control syncytium development. These findings support the concept that abnormalities in cardiomyocyte KIND2 expression or function may contribute to cardiomyopathies in humans.

  5. Embryonic Lethality Due to Arrested Cardiac Development in Psip1/Hdgfrp2 Double-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Hao Wang

    Full Text Available Hepatoma-derived growth factor (HDGF related protein 2 (HRP2 and lens epithelium-derived growth factor (LEDGF/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E 13.5. Histological examination revealed ventricular septal defect (VSD associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s, RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality

  6. A exposição crônica à fumaça do cigarro resulta em remodelação cardíaca e prejuízo da função ventricular em ratos Chronic cigarette smoke exposure results in cardiac remodeling and impaired ventricular function in rats

    Directory of Open Access Journals (Sweden)

    Édson Castardeli

    2005-04-01

    Full Text Available OBJETIVO: Determinar as alterações cardíacas estruturais e funcionais causadas pela exposição à fumaça do cigarro em ratos. MÉTODOS: Os animais foram aleatoriamente distribuídos em dois grupos: fumante (F, composto por 10 animais, expostos à fumaça do cigarro, na taxa de 40 cigarros/dia e controle (C, constituído por 10 animais não submetidos à exposição. Após 4 meses, os animais foram submetidos a estudo morfológico e funcional por meio do ecocardiograma. As variáveis estudadas foram analisadas pelo teste t ou pelo teste de Mann-Whitney. RESULTADOS: Os ratos fumantes apresentaram maior átrio esquerdo (F=4,2± 0,7mm; C=3,5±0,6mm; pOBJECTIVE: To determine the cardiac structural and functional alterations caused by cigarette smoke exposure in rats. METHODS: The animals were randomly distributed into the following 2 groups: 1 smokers (S, comprising 10 animals exposed to cigarette smoke at a rate of 40 cigarettes/day; and 2 control (C, comprising 10 animals not exposed to cigarette smoke. After 4 months, the animals underwent morphological and functional study with echocardiography. The variables studied were analyzed by use of the t test or the Mann-Whitney test. RESULTS: The smoking rats had a greater left atrium (S=4.2±0.7mm; C=3.5±0.6mm; P<0.05, and greater left ventricular diastolic (S=7.9±0.7mm; C=7.2±0.5mm; P<0.05 and systolic (S=4.1±0.5; C=3.4±0.5; P<0.05 diameters. The left ventricular mass index was greater in the smoking animals (S=1.5mg/kg±0.2; C=1.3mg/kg±0.2; P<0.05, and the ejection fraction (S=0.85±0.03; C=0.89±0.03; P<0.05 and the shortening fraction (S=47.8%±3.7; C=52.7%±4.6; P<0.05 were greater in the control group. No differences were observed in the diastolic transmitral flow variables (E wave, A wave, and E/A ratio. CONCLUSION: Chronic cigarette smoke exposure results in cardiac remodeling with a decrease in ventricular functional capacity.

  7. No-Regrets Remodeling, 2nd Edition

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-12-01

    No-Regrets Remodeling, sponsored by Oak Ridge National Laboratory, is an informative publication that walks homeowners and/or remodelers through various home remodeling projects. In addition to remodeling information, the publication provides instruction on how to incorporate energy efficiency into the remodeling process. The goal of the publication is to improve homeowner satisfaction after completing a remodeling project and to provide the homeowner with a home that saves energy and is comfortable and healthy.

  8. Epigenetic and lncRNA regulation of cardiac pathophysiology.

    Science.gov (United States)

    Chang, Ching-Pin; Han, Pei

    2016-07-01

    Our developmental studies provide an insight into the pathogenesis of heart failure in adults. These studies reveal a mechanistic link between fetal cardiomyocytes and pathologically stressed adult cardiomyocytes at the level of chromatin regulation. In embryos, chromatin-regulating factors within the cardiomyocytes respond to developmental signals to program cardiac gene expression to promote cell proliferation and inhibit premature cell differentiation. In the neonatal period, the activity of these developmental chromatin regulators is quickly turned off in cardiomyocytes, coinciding with the cessation of cell proliferation and advance in cell differentiation toward adult maturity. When the mature hearts are pathologically stressed, those chromatin regulators essential for cardiomyocyte development in embryos are reactivated, triggering gene reprogramming to a fetal-like state and pathological cardiac hypertrophy. Furthermore, in the study of chromatin regulation and cardiac gene expression, we identified a long noncoding RNA that interacts with chromatin remodeling factor to regulate the cardiac response to environmental changes. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26969820

  9. Prenatal programming: adverse cardiac programming by gestational testosterone excess.

    Science.gov (United States)

    Vyas, Arpita K; Hoang, Vanessa; Padmanabhan, Vasantha; Gilbreath, Ebony; Mietelka, Kristy A

    2016-01-01

    Adverse events during the prenatal and early postnatal period of life are associated with development of cardiovascular disease in adulthood. Prenatal exposure to excess testosterone (T) in sheep induces adverse reproductive and metabolic programming leading to polycystic ovarian syndrome, insulin resistance and hypertension in the female offspring. We hypothesized that prenatal T excess disrupts insulin signaling in the cardiac left ventricle leading to adverse cardiac programming. Left ventricular tissues were obtained from 2-year-old female sheep treated prenatally with T or oil (control) from days 30-90 of gestation. Molecular markers of insulin signaling and cardiac hypertrophy were analyzed. Prenatal T excess increased the gene expression of molecular markers involved in insulin signaling and those associated with cardiac hypertrophy and stress including insulin receptor substrate-1 (IRS-1), phosphatidyl inositol-3 kinase (PI3K), Mammalian target of rapamycin complex 1 (mTORC1), nuclear factor of activated T cells -c3 (NFATc3), and brain natriuretic peptide (BNP) compared to controls. Furthermore, prenatal T excess increased the phosphorylation of PI3K, AKT and mTOR. Myocardial disarray (multifocal) and increase in cardiomyocyte diameter was evident on histological investigation in T-treated females. These findings support adverse left ventricular remodeling by prenatal T excess. PMID:27328820

  10. An integrated electromechanical-growth heart model for simulating cardiac therapies.

    Science.gov (United States)

    Lee, Lik Chuan; Sundnes, Joakim; Genet, Martin; Wenk, Jonathan F; Wall, Samuel T

    2016-08-01

    An emerging class of models has been developed in recent years to predict cardiac growth and remodeling (G&R). We recently developed a cardiac G&R constitutive model that predicts remodeling in response to elevated hemodynamics loading, and a subsequent reversal of the remodeling process when the loading is reduced. Here, we describe the integration of this G&R model to an existing strongly coupled electromechanical model of the heart. A separation of timescale between growth deformation and elastic deformation was invoked in this integrated electromechanical-growth heart model. To test our model, we applied the G&R scheme to simulate the effects of myocardial infarction in a realistic left ventricular (LV) geometry using the finite element method. We also simulate the effects of a novel therapy that is based on alteration of the infarct mechanical properties. We show that our proposed model is able to predict key features that are consistent with experiments. Specifically, we show that the presence of a non-contractile infarct leads to a dilation of the left ventricle that results in a rightward shift of the pressure volume loop. Our model also predicts that G&R is attenuated by a reduction in LV dilation when the infarct stiffness is increased. PMID:26376641

  11. Serum myoglobin after cardiac catheterisation.

    OpenAIRE

    McComb, J. M.; McMaster, E A

    1982-01-01

    Study of 80 consecutive patients undergoing elective diagnostic cardiac catheterisation showed that after the procedure 25 (31%) developed myoglobinaemia. This was attributed to complications of the catheterisation in two. The remaining 23 had received premedication by intramuscular injection. In patients without intramuscular injections myoglobinaemia did not occur after uncomplicated cardiac catheterisation. The study did not support the proposition that cardiac catheterisation results in m...

  12. Biomaterials for cardiac regeneration

    CERN Document Server

    Ruel, Marc

    2015-01-01

    This book offers readers a comprehensive biomaterials-based approach to achieving clinically successful, functionally integrated vasculogenesis and myogenesis in the heart. Coverage is multidisciplinary, including the role of extracellular matrices in cardiac development, whole-heart tissue engineering, imaging the mechanisms and effects of biomaterial-based cardiac regeneration, and autologous bioengineered heart valves. Bringing current knowledge together into a single volume, this book provides a compendium to students and new researchers in the field and constitutes a platform to allow for future developments and collaborative approaches in biomaterials-based regenerative medicine, even beyond cardiac applications. This book also: Provides a valuable overview of the engineering of biomaterials for cardiac regeneration, including coverage of combined biomaterials and stem cells, as well as extracellular matrices Presents readers with multidisciplinary coverage of biomaterials for cardiac repair, including ...

  13. Assembly of the Cardiac Intercalated Disk during Pre- and Postnatal Development of the Human Heart

    Science.gov (United States)

    Vreeker, Arnold; van Stuijvenberg, Leonie; Hund, Thomas J.; Mohler, Peter J.; Nikkels, Peter G. J.; van Veen, Toon A. B.

    2014-01-01

    Background In cardiac muscle, the intercalated disk (ID) at the longitudinal cell-edges of cardiomyocytes provides as a macromolecular infrastructure that integrates mechanical and electrical coupling within the heart. Pathophysiological disturbance in composition of this complex is well known to trigger cardiac arrhythmias and pump failure. The mechanisms underlying assembly of this important cellular domain in human heart is currently unknown. Methods We collected 18 specimens from individuals that died from non-cardiovascular causes. Age of the specimens ranged from a gestational age of 15 weeks through 11 years postnatal. Immunohistochemical labeling was performed against proteins comprising desmosomes, adherens junctions, the cardiac sodium channel and gap junctions to visualize spatiotemporal alterations in subcellular location of the proteins. Results Changes in spatiotemporal localization of the adherens junction proteins (N-cadherin and ZO-1) and desmosomal proteins (plakoglobin, desmoplakin and plakophilin-2) were identical in all subsequent ages studied. After an initial period of diffuse and lateral labelling, all proteins were fully localized in the ID at approximately 1 year after birth. Nav1.5 that composes the cardiac sodium channel and the gap junction protein Cx43 follow a similar pattern but their arrival in the ID is detected at (much) later stages (two years for Nav1.5 and seven years for Cx43, respectively). Conclusion Our data on developmental maturation of the ID in human heart indicate that generation of the mechanical junctions at the ID precedes that of the electrical junctions with a significant difference in time. In addition arrival of the electrical junctions (Nav1.5 and Cx43) is not uniform since sodium channels localize much earlier than gap junction channels. PMID:24733085

  14. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    Science.gov (United States)

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  15. Methods of estimating the state of the mechanisms of regulation of cardiac activity for girls 9-10 years of age during physical training aimed at developing endurance

    OpenAIRE

    Samokih I.I.

    2012-01-01

    Are considered indicators of regulation of cardiac activity proposed D.N. Davidenko et al. (1984). It is established age-related indicators in girls from 9 to 10 years. It is shown that in the process of double-entry physical training with the implementation of priority endurance exercise significantly improves the efficiency of regulation of cardiac activity for girls. The expediency of the lessons of physical culture directed on the priority of development endurance to improve the physical ...

  16. Physiological and pathological cardiac hypertrophy.

    Science.gov (United States)

    Shimizu, Ippei; Minamino, Tohru

    2016-08-01

    The heart must continuously pump blood to supply the body with oxygen and nutrients. To maintain the high energy consumption required by this role, the heart is equipped with multiple complex biological systems that allow adaptation to changes of systemic demand. The processes of growth (hypertrophy), angiogenesis, and metabolic plasticity are critically involved in maintenance of cardiac homeostasis. Cardiac hypertrophy is classified as physiological when it is associated with normal cardiac function or as pathological when associated with cardiac dysfunction. Physiological hypertrophy of the heart occurs in response to normal growth of children or during pregnancy, as well as in athletes. In contrast, pathological hypertrophy is induced by factors such as prolonged and abnormal hemodynamic stress, due to hypertension, myocardial infarction etc. Pathological hypertrophy is associated with fibrosis, capillary rarefaction, increased production of pro-inflammatory cytokines, and cellular dysfunction (impairment of signaling, suppression of autophagy, and abnormal cardiomyocyte/non-cardiomyocyte interactions), as well as undesirable epigenetic changes, with these complex responses leading to maladaptive cardiac remodeling and heart failure. This review describes the key molecules and cellular responses involved in physiological/pathological cardiac hypertrophy. PMID:27262674

  17. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  18. Implantable Defibrillators Improve Survival in Patients With Mildly Symptomatic Heart Failure Receiving Cardiac Resynchronization Therapy

    DEFF Research Database (Denmark)

    Gold, Michael R; Daubert, Jean-Claude; Abraham, William T;

    2013-01-01

    Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular remodeling in selected populations with heart failure. These benefits have been noted with both CRT-pacemakers as well as those devices with defibrillator backup (CRT...

  19. Computerized prediction of intensive care unit discharge after cardiac surgery: development and validation of a Gaussian processes model

    Directory of Open Access Journals (Sweden)

    Meyfroidt Geert

    2011-10-01

    Full Text Available Abstract Background The intensive care unit (ICU length of stay (LOS of patients undergoing cardiac surgery may vary considerably, and is often difficult to predict within the first hours after admission. The early clinical evolution of a cardiac surgery patient might be predictive for his LOS. The purpose of the present study was to develop a predictive model for ICU discharge after non-emergency cardiac surgery, by analyzing the first 4 hours of data in the computerized medical record of these patients with Gaussian processes (GP, a machine learning technique. Methods Non-interventional study. Predictive modeling, separate development (n = 461 and validation (n = 499 cohort. GP models were developed to predict the probability of ICU discharge the day after surgery (classification task, and to predict the day of ICU discharge as a discrete variable (regression task. GP predictions were compared with predictions by EuroSCORE, nurses and physicians. The classification task was evaluated using aROC for discrimination, and Brier Score, Brier Score Scaled, and Hosmer-Lemeshow test for calibration. The regression task was evaluated by comparing median actual and predicted discharge, loss penalty function (LPF ((actual-predicted/actual and calculating root mean squared relative errors (RMSRE. Results Median (P25-P75 ICU length of stay was 3 (2-5 days. For classification, the GP model showed an aROC of 0.758 which was significantly higher than the predictions by nurses, but not better than EuroSCORE and physicians. The GP had the best calibration, with a Brier Score of 0.179 and Hosmer-Lemeshow p-value of 0.382. For regression, GP had the highest proportion of patients with a correctly predicted day of discharge (40%, which was significantly better than the EuroSCORE (p Conclusions A GP model that uses PDMS data of the first 4 hours after admission in the ICU of scheduled adult cardiac surgery patients was able to predict discharge from the ICU as a

  20. Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, H.J.; Ouyang, W.; Liu, J.H.; Sun, Y.G.; Hu, R.; Huang, L.H.; Xian, J.L. [Southern Medical University, Department of Nuclear Medicine, Zhujiang Hospital, Guangzhou, China, Department of Nuclear Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou (China); Jing, C.F.; Zhou, M.J. [Sun Yat-Sen University, South China Sea Marine Biotechnology, National Engineering Research Center, Guangzhou, China, National Engineering Research Center, South China Sea Marine Biotechnology, Sun Yat-Sen University, Guangzhou (China)

    2014-04-11

    Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

  1. Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

    International Nuclear Information System (INIS)

    Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy

  2. An overview of cardiac morphogenesis.

    Science.gov (United States)

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-11-01

    Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling. PMID:24138816

  3. Changes in microRNAs expression are involved in age-related atrial structural remodeling and atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    XU Guo-jun; GAN Tian-yi; TANG Bao-peng; CHEN Zu-heng; Mahemuti Ailiman; ZHOU Xian-hui; JIANG Tao

    2013-01-01

    Background Small noncoding microRNAs regulate gene expression in cardiac development and disease and have been implicated in the aging process and in the regulation of extracellular matrix proteins.However,their role in age-related cardiac remodeling and atrial fibrillation (AF) was not well understood.The present study was designed to decipher molecular mechanisms underlying age-related atrial structural remodeling and AF.Methods Three groups of dogs were studied:adult and aged dogs in sinus rhythm and with persistent AF induced by rapid atrial pacing.The expressions of microRNAs were measured by quantitative real-time polymerase chain reaction.Pathohistological and ultrastructural changes were tested by light and electron microscopy.Apoptosis index of myocytes was detected by TUNEL.Results Samples of atrial tissue showed the abnormal pathohistological and ultrastructural changes,the accelerated fibrosis,and apoptosis with aging and/or in AF dogs.Compared to the adult group,the expressions of microRNAs-21 and -29 were significantly increased,whereas the expressions of microRNAs-1 and-133 showed obvious downregulation tendency in the aged group.Compared to the aged group,the expressions of microRNAs-1,-21,and-29 was significantly increased in the old group in AF; contrastingly,the expressions of microRNA-133 showed obvious downregulation tendency.Conclusion These multiple aberrantly expressed microRNAs may be responsible for modulating the transition from adaptation to pathological atrial remodeling with aging and/or in AF.

  4. The effects of cytoskeletal disruption and mechanical load on cardiac conduction

    OpenAIRE

    Wright, Adam Thomas

    2010-01-01

    Myocardial disease is often associated with altered cardiac conduction and increased incidence of arrhythmia. Underlying mechanisms responsible for changes in conduction include altered calcium handling, myocardial remodeling, and mechanically induced changes in electrophysiology. The goal of this work was to utilize optical mapping experimental techniques and genetically modified mouse models to investigate two of these mechanisms: myocardial remodeling associated with disruption of the cyto...

  5. Collagen scaffold remodeling by human mesenchymal stem cells

    OpenAIRE

    Han, SJ; Chan, BP

    2011-01-01

    Type I collagen has been widely used as scaffold for tissue engineering because of its excellent biocompatibility and negligible immunogenicity. We previously have developed a collagen microencapsulation technology entrapping many cells including human mesenchymal stem cells (hMSCs) in microspheres made of nanofibrous collagen meshwork. Nevertheless, little is understood about how stem cells interact with and remodel the collagen meshwork. This study aims to investigate collagen remodeling by...

  6. MicroRNA与心血管重构%MicroRNA and cardiovascular remodeling

    Institute of Scientific and Technical Information of China (English)

    邓璧

    2013-01-01

    MicroRNA is a short (18-25 nuucleotides) and single-stranded non-coding RNA which is involved in almost all pathological and physiological process of diseases.Cardiovascular remodeling is the pathological basis of development of multiple cardiovascular diseases,in which microRNA plays an important role.In cardiac diseases,microRNAs affect myocardial cell hypertrophy,apoptosis,and interstitial fibrosis through a variety of mechanisms.In vascular remodeling diseases,microRNAs regulate proliferation and secretion of vascular smooth muscle cells through multiple signaling pathways.%MicroRNA为短小(18~25个核苷酸组成)单链非编码RNAs,几乎参与所有疾病的病理生理过程.心血管重构是多种心血管疾病发生与发展的病理基础,而microRNA在心血管重构中起重要调控作用.在心肌性疾病中,microRNA通过多种机制影响心肌细胞肥大、凋亡和间质纤维化;在血管重构性疾病中,不同microRNA通过多条信号通路调节血管平滑肌细胞增殖和分泌.

  7. Differences in coronary artery disease by CT angiography between patients developing unstable angina pectoris vs. major adverse cardiac events

    International Nuclear Information System (INIS)

    Highlights: • Patients developing UAP had overall more atherosclerosis as patients without any events. • Patients developing MACE had only more mixed plaque as those developing UAP. • Different atherosclerotic plaque components by CTA carry different prognostic value. - Abstract: Objective: CT angiography (CTA) has prognostic value in patients. But it is unknown whether differences in atherosclerosis by CTA predict the development of unstable angina pectoris (UAP) vs. major adverse cardiac events (MACE). Methods: We followed patients undergoing CTA as part of their acute chest pain work-up. Primary outcome was the development of UAP or MACE (cardiac death, myocardial infarction, revascularization) during a minimum follow-up of 12-months. CTAs were assessed for extent and composition of coronary plaque and stenosis. Ordinal regression with a 3-level outcome (no events, UAP, MACE) was applied. Results: Among 315 patients, 22 developed UAP and 31 MACE. While UAP patients had higher atherosclerosis burden with respect to all assessed features compared to patients with no events (p ≤ 0.02), only mixed plaque extent was significantly different between UAP and MACE patients (p = 0.02). The odds ratio was 4.55 for being in a higher disease-level comparing patients with low extent to those with no mixed plaque, and 3.02 comparing patients with high to those with low. These findings remained after adjustments for potential confounders. Conclusion: The extent of mixed coronary plaque is different between patients who develop UAP vs. MACE, supporting the hypothesis that it is a more culprit morphology

  8. Differences in coronary artery disease by CT angiography between patients developing unstable angina pectoris vs. major adverse cardiac events

    Energy Technology Data Exchange (ETDEWEB)

    Schlett, Christopher L. [Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg (Germany); Nance, John W. Jr. [Heart and Vascular Center, Medical University of South Carolina, Charleston, SC (United States); The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Hospital, Baltimore, MD (United States); Schoepf, U. Joseph, E-mail: schoepf@musc.edu [Heart and Vascular Center, Medical University of South Carolina, Charleston, SC (United States); O’Brien, Terrence X. [Heart and Vascular Center, Medical University of South Carolina, Charleston, SC (United States); The Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC (United States); Ebersberger, Ullrich [Heart and Vascular Center, Medical University of South Carolina, Charleston, SC (United States); Department of Cardiology and Intensive Care Medicine, Heart Centre Munich-Bogenhausen, Munich (Germany); Headden, Gary F. [Heart and Vascular Center, Medical University of South Carolina, Charleston, SC (United States); Hoffmann, Udo [Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Bamberg, Fabian [Cardiac MR PET CT Program, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States); Department of Radiology, University of Munich, Grosshadern Campus, and Munich Heart Alliance, Munich (Germany); Department of Radiology, University of Tuebingen (Germany)

    2014-07-15

    Highlights: • Patients developing UAP had overall more atherosclerosis as patients without any events. • Patients developing MACE had only more mixed plaque as those developing UAP. • Different atherosclerotic plaque components by CTA carry different prognostic value. - Abstract: Objective: CT angiography (CTA) has prognostic value in patients. But it is unknown whether differences in atherosclerosis by CTA predict the development of unstable angina pectoris (UAP) vs. major adverse cardiac events (MACE). Methods: We followed patients undergoing CTA as part of their acute chest pain work-up. Primary outcome was the development of UAP or MACE (cardiac death, myocardial infarction, revascularization) during a minimum follow-up of 12-months. CTAs were assessed for extent and composition of coronary plaque and stenosis. Ordinal regression with a 3-level outcome (no events, UAP, MACE) was applied. Results: Among 315 patients, 22 developed UAP and 31 MACE. While UAP patients had higher atherosclerosis burden with respect to all assessed features compared to patients with no events (p ≤ 0.02), only mixed plaque extent was significantly different between UAP and MACE patients (p = 0.02). The odds ratio was 4.55 for being in a higher disease-level comparing patients with low extent to those with no mixed plaque, and 3.02 comparing patients with high to those with low. These findings remained after adjustments for potential confounders. Conclusion: The extent of mixed coronary plaque is different between patients who develop UAP vs. MACE, supporting the hypothesis that it is a more culprit morphology.

  9. Effects of Perindopril on Left Ventricular Remodeling and Osteopontin Expression in Rats With Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction. Methods In this study male adult SD rats were randomly divided into 3groups: sham-operation group, MI-saline group and MI-perindopril group. Left anterior descending artery was ligated to generate myocardial infarction. Perindopril (2 mg/kg body weight/day) was administered from the next day of MI.Four weeks later, left ventricular diameter (LVEDD and LVESD) and left ventricular ejection fraction was estimated with echocardiography, LVSP, LVEDP and ± dp/dtmax was detected with hemodynamic measurement, cardiomyocyte diameter and interstitial fibrosis infiltration were evaluated with histological methods, and myocardium osteopontin protein expression level was detected with western blot. Results ①Compared with the sham-operation group, all rats with MI developed significant systolic and diastolic dysfunction, as was indicated by decreased LVEF, LVSP and ± dp/dtmax, as well as increased LVEDP. ②Rats with MI showed significantly dilated left ventricles and higher ventricular weight / body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. ③Perindopril treatment partly prevented cardiac dysfunction and left ventricular remodeling as indicated by the parameters mentioned above. ④No osteopontin protein was detected in myocardium of sham-operation rats. In rats with MI, high level osteopontin protein expression was significantly inhibited by perindopril treatment. Conclusions In rats with MI, perindopril treatment significantly prevented left ventricular remodeling and myocardium osteopontin protein expression.

  10. Regulation of Connective Tissue Growth Factor and Cardiac Fibrosis by an SRF/MicroRNA-133a Axis.

    Directory of Open Access Journals (Sweden)

    Aude Angelini

    Full Text Available Myocardial fibrosis contributes to the remodeling of heart and the loss of cardiac function leading to heart failure. SRF is a transcription factor implicated in the regulation of a large variety of genes involved in cardiac structure and function. To investigate the impact of an SRF overexpression in heart, we developed a new cardiac-specific and tamoxifen-inducible SRF overexpression mouse model by the Cre/loxP strategy. Here, we report that a high level overexpression of SRF leads to severe modifications of cardiac cytoarchitecture affecting the balance between cardiomyocytes and cardiac fibroblasts and also a profound alteration of cardiac gene expression program. The drastic development of fibrosis was characterized by intense sirius red staining and associated with an increased expression of genes encoding extracellular matrix proteins such as fibronectin, procollagen type 1α1 and type 3α1 and especially connective tissue growth factor (CTGF. Furthermore miR-133a, one of the most predominant cardiac miRNAs, is strongly downregulated when SRF is overexpressed. By comparison a low level overexpression of SRF has minor impact on these different processes. Investigation with miR-133a, antimiR-133a and AdSRF-VP16 experiments in H9c2 cardiac cells demonstrated that: 1-miR-133a acts as a repressor of SRF and CTGF expression; 2-a simultaneous overexpression of SRF by AdSRF-VP16 and inhibition of miR-133a by a specific antimiR increase CTGF expression; 3-miR-133a overexpression can block the upregulation of CTGF induced by AdSRF-VP16. Taken together, these findings reveal a key role of the SRF/CTGF/miR-133a axis in the regulation of cardiac fibrosis.

  11. Cardiac MR: recent technical developments%心脏磁共振技术新进展

    Institute of Scientific and Technical Information of China (English)

    赵世华

    2014-01-01

    近年来,除了常规的心脏磁共振成像(cardiac magnetic resonance imaging,CMR)技术(包括解剖成像、功能电影成像及对比剂延迟强化)以外,涌现了许多新的CMR诊断技术,如定量成像技术(quantitative imaging)及非对比剂增强CMR(non-contrast imaging).前者包括弛豫特性定量(T1、T2mapping)、血流定量(4Dflow)及弥散张量成像(diffusion tensor imaging,DTI)等;后者包括非对比剂增强全心磁共振冠脉成像(whole heart MR coronary angiography,WH-MRCA)及血氧水平依赖(blood oxygenation level dependent,BOLD)的CMR等.

  12. Development of a mobile HIS/PACS workstation to assist critical cardiac patients in an intensive care unit

    Science.gov (United States)

    Gutierrez, Marco A.; Cestari, Idagene A.; Hamamoto, Gina; Bacht, Simão; Rebelo, Marina S.; Silva, João E. M. M.; Lage, Silvia G.

    2008-03-01

    The current study describes the experience in the implementation of a mobile HIS/PACS workstation to assist critical cardiac patients in an Intensive Care Unit (ICU). Recently, mobile devices connected to a WiFi network were incorporated to the Hospital information System, providing the same functionalities of common desktop counterpart. However, the use of commercially devices like PDAs and Pocket PCs presented a series of problems that are more emphasized in the ICUs 1) low autonomy of the batteries, which need constant recharges; 2) low robustness of the devices; 3) insufficient display area to show medical images and vital signals; 4) data entry remains a major problem and imposes an extra time consumption to the staff; 5) high cost when fully equipped with WiFi connection, optical reader to access bar codes and memory. To address theses problems we developed a mobile workstation (MedKart) that provides access the HIS and PACS systems, with all resources and an ergonomic and practical design to be used by physicians and nurses inside the ICU. The system fulfills the requirements to assist, in the point-of-care, critical cardiac patients in Intensive Care Units.

  13. Role of inflammation in the development of cardiac autonomic disfunction in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    D. S. Novikova

    2008-01-01

    Full Text Available Objective. To evaluate role of inflammation in pathogenesis of cardiac autonomic dysfunction assessed by heart rate variability (HRV analyses, in patients (pts with systemic lupus erythematosus (SLE. Material and methods. 75 female pts with SLE aged before 55 years were included. Control group consisted of 32 healthy women of comparable age. Clinical symptoms, activity degree and main cardiovascular risk factors were assessed. Common carotid duplex scanning with measurement of intima-media thickness, echocardiography, 24 h ECG ambulatory recording with determination of time domain parameters, evaluation of serum inflammation markers level (CRP, IL-6, TNFa were performed. Results. HRV time domain parameters adjusted by McanNN - SDNNn%, SDNNin%, rMSSDn%, pNN50% in women with SLE were lower than in healthy control. HRV parameters inversely correlated with inflammation markers in SLE (p<0,05. SLE pts were divided into 4 groups: 1 (n=12 - pts with low HRV parameters and high level of IL-6; 2 (n=13 - low HRV and normal IL-6; 3 (n=6 - normal HRV and high IL-6; 4 (n=44 - normal HRV and IL-6. SLEDA1 2K, left atrium size, levels of markers of inflammation in group 1 were higher, then in group 4 (p<0,05. Hypertension, dyslipidemia, smoking and subclinical atherosclerosis of carotid arteries were more frequent in group 2 compared to group 4 (p<0,05. Conclusion. These results suggest important role of autoimmune inflammation in pathogenesis of cardiac autonomic dysfunction in SLE pts with high disease activity and traditional cardiovascular risk factor, atherosclerotic changes - in low SLE activity. HRV, traditional cardiovascular risk factors and inflammatory markers combined measurement can help to identify subjects at risk of cardiovascular mortality among SLE pts.

  14. Protective effect of prostacyclin against pre-cardiac edema caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin and a thromboxane receptor agonist in developing zebrafish.

    Science.gov (United States)

    Nijoukubo, Daisuke; Tanaka, Yasuaki; Okuno, Yuki; Yin, Guojun; Kitazawa, Takio; Peterson, Richard E; Kubota, Akira; Teraoka, Hiroki

    2016-08-01

    The role of prostaglandin pathways has been suggested in some toxicological responses to dioxins. Cyclooxygenase type 2b (COX2b), thromboxane synthase, and the thromboxane receptor (TP) pathway have been implicated in mediating 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced pre-cardiac edema in developing zebrafish at 55 h post fertilization (hpf). Pre-cardiac edema refers to edema located in a small cavity between the heart and body wall of zebrafish eleutheroembryos. In the present study, we assessed the role of prostacyclin, which counteracts some biological effects of thromboxane, in TCDD-induced pre-cardiac edema. Pre-cardiac edema induced by TCDD exposure (0.5 and 1 ppb) beginning at 24 hpf was markedly inhibited by exposure to beraprost (5 and 10 μM), a prostacyclin receptor (IP) agonist, beginning at 33 hpf. The preventive effect of beraprost was reduced by exposure to CAY10441 (10 μM), an IP antagonist starting at 33 hpf. Knockdowns of the IP receptor (IP-KD) with two different morpholinos caused edema by themselves and enhanced pre-cardiac edema caused by the low concentration of TCDD (0.5 ppb). On the other hand, short exposure beginning at 48 hpf to U46619 (7.5-30 μM), a thromboxane receptor agonist caused pre-cardiac edema, which was inhibited by exposure beginning at 48 hpf to both ICI-192,605 (24 μM), a TP antagonist, and beraprost. Expression of prostacyclin synthase was increased from fertilization, plateaued by 48 hpf, and was maintained until at least 96 hpf. Overall, the results demonstrate a preventive effect of prostacyclin on TCDD-induced pre-cardiac edema in developing zebrafish. PMID:27174823

  15. Metabolic remodeling associated with subchronic doxorubicin cardiomyopathy

    International Nuclear Information System (INIS)

    Doxorubicin (Adriamycin®) is a potent and broad-spectrum antineoplastic agent, the clinical utility of which is restricted by a cumulative and progressive cardiomyopathy that develops with repeated dosing. Fundamental to the cardiac failure is an interference with mitochondrial respiration and inhibition of oxidative phosphorylation. Global gene expression arrays in cardiac tissue indicate that inhibition of mitochondrial oxidative phosphorylation by doxorubicin (DOX) is accompanied by a decreased expression of genes related to aerobic fatty acid oxidation and a corresponding increase in expression of genes involved in anaerobic glycolysis, possibly as an alternate source for ATP production. The aim of this investigation was to determine whether this is also manifest at the metabonomic level as a switch in metabolic flux in cardiac tissue, and whether this can be averted by co-administering the cardioprotective drug, dexrazoxane (DZR). 13C-isotopomer analysis of isolated perfused hearts from male Sprague-Dawley rats receiving 6 weekly s.c. injections of 2 mg/kg DOX demonstrated a shift from the preferential oxidation of fatty acids to enhanced oxidation of glucose and lactate plus pyruvate, indicative of a compensatory shift towards increased pyruvate dehydrogenase activity. Substrate-selective isotopomer analysis combined with western blots indicate an inhibition of long-chain fatty acid oxidation and not MCAD activity or fatty acyl-carnitine transport. Co-administering DZR averted many treatment-related changes in cardiac substrate metabolism, consistent with DZR being an effective cardioprotective agent against DOX-induced cardiomyopathy. This switch in substrate metabolism resembles that described for other models of cardiac failure; accordingly, this change in metabolic flux may represent a general compensatory response of cardiac tissue to imbalances in bioenergetic demand and supply, and not a characteristic unique to DOX-induced cardiac failure itself.

  16. Validation, optimisation, and application data in support of the development of a targeted selected ion monitoring assay for degraded cardiac troponin T.

    Science.gov (United States)

    Streng, Alexander S; de Boer, Douwe; Bouwman, Freek G; Mariman, Edwin C M; Scholten, Arjen; van Dieijen-Visser, Marja P; Wodzig, Will K W H

    2016-06-01

    Cardiac troponin T (cTnT) fragmentation in human serum was investigated using a newly developed targeted selected ion monitoring assay, as described in the accompanying article: "Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T" [1]. This article presents data describing aspects of the validation and optimisation of this assay. The data consists of several figures, an excel file containing the results of a sequence identity search, and a description of the raw mass spectrometry (MS) data files, deposited in the ProteomeXchange repository with id PRIDE: PXD003187. PMID:26977445

  17. High Methionine Diet Poses Cardiac Threat: A Molecular Insight.

    Science.gov (United States)

    Chaturvedi, Pankaj; Kamat, Pradip K; Kalani, Anuradha; Familtseva, Anastasia; Tyagi, Suresh C

    2016-07-01

    High methionine diet (HMD) for example red meat which includes lamb, beef, pork can pose cardiac threat and vascular dysfunction but the mechanisms are unclear. We hypothesize that a diet rich in methionine can malfunction the cardiovascular system in three ways: (1) by augmenting oxidative stress; (2) by inflammatory manifestations; and (3) by matrix/vascular remodeling. To test this hypothesis we used four groups of mice: (1) WT; (2) WT + methionine; (3) CBS(+/-) ; (4) CBS(+/-) +methionine. We observed high oxidative stress in mice fed with methionine which was even higher in CBS(+/-) and CBS(+/-) +methionine. Higher oxidative stress was indicated by high levels of SOD-1 in methionine fed mouse hearts whereas IL-1β, IL-6, TNFα, and TLR4 showed high inflammatory manifestations. The upregulated levels of eNOS/iNOS and upregulated levels of MMP2/MMP9 along with high collagen deposition indicated vascular and matrix remodeling in methionine fed mouse. We evaluated the cardiac function which was dysregulated in the mice fed with HMD. These mice had decreased ejection fraction and left ventricular dysfunction which subsequently leads to adverse cardiac remodeling. In conclusion, our study clearly shows that HMD poses a cardiac threat by increasing oxidative stress, inflammatory manifestations, matrix/vascular remodeling, and decreased cardiac function. J. Cell. Physiol. 231: 1554-1561, 2016. © 2015 Wiley Periodicals, Inc. PMID:26565991

  18. Developing a visualized patient-centered, flow-based and objective-oriented care path of cardiac catheterization examination.

    Science.gov (United States)

    Kuo, Ming Chuan; Chang, Polun

    2009-01-01

    It has been known that visualization is a user-preferred and more meaningful interface of information systems. To reduce the anxiety and uncertainty of patients, we transformed the sophisticated process of cardiac catheterization into visualized information. The Microsoft Visio 2003 and Excel 2003 with the VBA automation tool were used to design a process flow of Cardiac Catheterization. The results show the technical feasibility and potentials helpful for patient to realize the nursing process of cardiac catheterization. PMID:19593031

  19. The developing role of fetal magnetic resonance imaging in the diagnosis of congenital cardiac anomalies: A systematic review

    Directory of Open Access Journals (Sweden)

    Rohit S Loomba

    2011-01-01

    Full Text Available Advances in the fetal magnetic resonance imaging (MRI over the last few years have resulted in the exploring the use of fetal MRI to detect congenital cardiac anomalies. Early detection of congenital cardiac anomalies can help more appropriately manage the infant′s delivery and neonatal management. MRI offers anatomical and functional studies and is a safe adjunct that can help more fully understand a fetus′ cardiac anatomy. It is important for the obstetricians and pediatric cardiologists to be aware of the recent advancements in fetal MRI and it`s potential utility in diagnosing congenital cardiac anomalies.

  20. The developing role of fetal magnetic resonance imaging in the diagnosis of congenital cardiac anomalies: A systematic review

    International Nuclear Information System (INIS)

    Advances in the fetal magnetic resonance imaging (MRI) over the last few years have resulted in the exploring the use of fetal MRI to detect congenital cardiac anomalies. Early detection of congenital cardiac anomalies can help more appropriately manage the infant's delivery and neonatal management. MRI offers anatomical and functional studies and is a safe adjunct that can help more fully understand a fetus' cardiac anatomy. It is important for the obstetricians and pediatric cardiologists to be aware of the recent advancements in fetal MRI and it's potential utility in diagnosing congenital cardiac anomalies

  1. Development of a Comprehensive Sequencing Assay for Inherited Cardiac Condition Genes.

    Science.gov (United States)

    Pua, Chee Jian; Bhalshankar, Jaydutt; Miao, Kui; Walsh, Roddy; John, Shibu; Lim, Shi Qi; Chow, Kingsley; Buchan, Rachel; Soh, Bee Yong; Lio, Pei Min; Lim, Jaclyn; Schafer, Sebastian; Lim, Jing Quan; Tan, Patrick; Whiffin, Nicola; Barton, Paul J; Ware, James S; Cook, Stuart A

    2016-02-01

    Inherited cardiac conditions (ICCs) are characterised by marked genetic and allelic heterogeneity and require extensive sequencing for genetic characterisation. We iteratively optimised a targeted gene capture panel for ICCs that includes disease-causing, putatively pathogenic, research and phenocopy genes (n = 174 genes). We achieved high coverage of the target region on both MiSeq (>99.8 % at ≥20× read depth, n = 12) and NextSeq (>99.9 % at ≥20×, n = 48) platforms with 100 % sensitivity and precision for single nucleotide variants and indels across the protein-coding target on the MiSeq. In the final assay, 40 out of 43 established ICC genes informative in clinical practice achieved complete coverage (100 % at ≥20×). By comparison, whole exome sequencing (WES; ∼80×), deep WES (∼500×) and whole genome sequencing (WGS; ∼70×) had poorer performance (88.1, 99.2 and 99.3 % respectively at ≥20×) across the ICC target. The assay described here delivers highly accurate and affordable sequencing of ICC genes, complemented by accessible cloud-based computation and informatics. See Editorial in this issue (DOI: 10.1007/s12265-015-9667-8 ). PMID:26888179

  2. Selection and collection of multi parameter physiological data for cardiac rhythm diagnostic algorithm development

    International Nuclear Information System (INIS)

    Automated diagnostic algorithms are used in implantable cardioverter-defibrillators (ICD's) to detect abnormal heart rhythms. Algorithms misdiagnose and improved specificity is needed to prevent inappropriate therapy. Knowledge engineering (KE) and artificial intelligence (AI) could improve this. A pilot study of KE was performed with artificial neural network (ANN) as AI system. A case note review analysed arrhythmic events stored in patients ICD memory. 13.2% patients received inappropriate therapy. The best ICD algorithm had sensitivity 1.00, specificity 0.69 (p<0.001 different to gold standard). A subset of data was used to train and test an ANN. A feed-forward, back-propagation network with 7 inputs, a 4 node hidden layer and 1 output had sensitivity 1.00, specificity 0.71 (p<0.001). A prospective study was performed using KE to list arrhythmias, factors and indicators for which measurable parameters were evaluated and results reviewed by a domain expert. Waveforms from electrodes in the heart and thoracic bio-impedance; temperature and motion data were collected from 65 patients during cardiac electrophysiological studies. 5 incomplete datasets were due to technical failures. We concluded that KE successfully guided selection of parameters and ANN produced a usable system and that complex data collection carries greater risk of technical failure, leading to data loss.

  3. Selection and collection of multi parameter physiological data for cardiac rhythm diagnostic algorithm development

    Energy Technology Data Exchange (ETDEWEB)

    Bostock, J.; Weller, P. [School of Informatics, City University London, London EC1V 0HB (United Kingdom); Cooklin, M., E-mail: jbostock1@msn.co [Cardiovascular Directorate, Guy' s and St. Thomas' NHS Foundation Trust, London, SE1 7EH (United Kingdom)

    2010-07-01

    Automated diagnostic algorithms are used in implantable cardioverter-defibrillators (ICD's) to detect abnormal heart rhythms. Algorithms misdiagnose and improved specificity is needed to prevent inappropriate therapy. Knowledge engineering (KE) and artificial intelligence (AI) could improve this. A pilot study of KE was performed with artificial neural network (ANN) as AI system. A case note review analysed arrhythmic events stored in patients ICD memory. 13.2% patients received inappropriate therapy. The best ICD algorithm had sensitivity 1.00, specificity 0.69 (p<0.001 different to gold standard). A subset of data was used to train and test an ANN. A feed-forward, back-propagation network with 7 inputs, a 4 node hidden layer and 1 output had sensitivity 1.00, specificity 0.71 (p<0.001). A prospective study was performed using KE to list arrhythmias, factors and indicators for which measurable parameters were evaluated and results reviewed by a domain expert. Waveforms from electrodes in the heart and thoracic bio-impedance; temperature and motion data were collected from 65 patients during cardiac electrophysiological studies. 5 incomplete datasets were due to technical failures. We concluded that KE successfully guided selection of parameters and ANN produced a usable system and that complex data collection carries greater risk of technical failure, leading to data loss.

  4. Indeterminacy of Spatiotemporal Cardiac Alternans

    CERN Document Server

    Zhao, Xiaopeng

    2007-01-01

    Cardiac alternans, a beat-to-beat alternation in action potential duration (at the cellular level) or in ECG morphology (at the whole heart level), is a marker of ventricular fibrillation, a fatal heart rhythm that kills hundreds of thousands of people in the US each year. Investigating cardiac alternans may lead to a better understanding of the mechanisms of cardiac arrhythmias and eventually better algorithms for the prediction and prevention of such dreadful diseases. In paced cardiac tissue, alternans develops under increasingly shorter pacing period. Existing experimental and theoretical studies adopt the assumption that alternans in homogeneous cardiac tissue is exclusively determined by the pacing period. In contrast, we find that, when calcium-driven alternans develops in cardiac fibers, it may take different spatiotemporal patterns depending on the pacing history. Because there coexist multiple alternans solutions for a given pacing period, the alternans pattern on a fiber becomes unpredictable. Usin...

  5. Common threads in cardiac fibrosis, infarct scar formation, and wound healing

    Directory of Open Access Journals (Sweden)

    Czubryt Michael P

    2012-11-01

    Full Text Available Abstract Wound healing, cardiac fibrosis, and infarct scar development, while possessing distinct features, share a number of key functional similarities, including extracellular matrix synthesis and remodeling by fibroblasts and myofibroblasts. Understanding the underlying mechanisms that are common to these processes may suggest novel therapeutic approaches for pathologic situations such as fibrosis, or defective wound healing such as hypertrophic scarring or keloid formation. This manuscript will briefly review the major steps of wound healing, and will contrast this process with how cardiac infarct scar formation or interstitial fibrosis occurs. The feasibility of targeting common pro-fibrotic growth factor signaling pathways will be discussed. Finally, the potential exploitation of novel regulators of wound healing and fibrosis (ski and scleraxis, will be examined.

  6. Methods of estimating the state of the mechanisms of regulation of cardiac activity for girls 9-10 years of age during physical training aimed at developing endurance

    Directory of Open Access Journals (Sweden)

    Samokih I.I.

    2012-02-01

    Full Text Available Are considered indicators of regulation of cardiac activity proposed D.N. Davidenko et al. (1984. It is established age-related indicators in girls from 9 to 10 years. It is shown that in the process of double-entry physical training with the implementation of priority endurance exercise significantly improves the efficiency of regulation of cardiac activity for girls. The expediency of the lessons of physical culture directed on the priority of development endurance to improve the physical health of school girls of primary school.

  7. Upregulation of MicroRNA-214 Contributes to the Development of Vascular Remodeling in Hypoxia-induced Pulmonary Hypertension Via Targeting CCNL2

    Science.gov (United States)

    Liu, HaiTao; Tao, Yin; Chen, Mai; Yu, Jin; Li, Wei-Jie; Tao, Ling; Li, Yan; Li, Fei

    2016-01-01

    Hypoxia-induced pulmonary hypertension (PH), which is characterized by vascular remodeling of blood vessels, is a significant complication of chronic obstructive pulmonary disease (COPD). In this study, we screened 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs) harvested from COPD patients with PH (n = 18) and normal controls (n = 15) and found that the expression of miR-214 was differentially expressed between these two groups. Additionally, cyclin L2 (CCNL2) was validated as a target of miR-214 in PASMCs using a luciferase assay. Based on real-time PCR, immunohistochemistry and western blot, the expression of CCNL2 was substantially downregulated in PASMCs from COPD patients with PH compared with those from normal controls. Moreover, the relationship between miRNA and mRNA expression was confirmed using real-time PCR and western blot in PASMCs transfected with miR-214 mimics. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing cell apoptosis, and this effect was mediated by the downregulation of CCNL2. Exposure of PASMCs to hypoxia significantly increased the expression of miR-214, decreased the expression of CCNL2, and promoted cell proliferation. However, these effects were significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated CCNL2 expression. PMID:27381447

  8. Simulated Microgravity and Recovery-Induced Remodeling of the Left and Right Ventricle

    Science.gov (United States)

    Zhong, Guohui; Li, Yuheng; Li, Hongxing; Sun, Weijia; Cao, Dengchao; Li, Jianwei; Zhao, Dingsheng; Song, Jinping; Jin, Xiaoyan; Song, Hailin; Yuan, Xinxin; Wu, Xiaorui; Li, Qi; Xu, Qing; Kan, Guanghan; Cao, Hongqing; Ling, Shukuan; Li, Yingxian

    2016-01-01

    Physiological adaptations to microgravity involve alterations in cardiovascular systems. These adaptations result in cardiac remodeling and orthostatic hypotension. However, the response of the left ventricle (LV) and right ventricle (RV) following hindlimb unloading (HU) and hindlimb reloading (HR) is not clear and the underlying mechanism remains to be understood. In this study, three groups of mice were subjected to HU by tail suspension for 28 days. Following this, two groups were allowed to recover for 7 or 14 days. The control group was treated equally, with the exception of tail suspension. Echocardiography was performed to detect the structure and function changes of heart. Compared with the control, the HU group of mice showed reduced LV-EF (ejection fraction), and LV-FS (fractional shortening). However, mice that were allowed to recover for 7 days after HU (HR-7d) showed increased LVIDs (systolic LV internal diameter) and LV Vols (systolic LV volume). Mice that recovered for 14 days (HR-14d) returned to the normal state. In comparison, RV-EF and RV-FS didn't recover to the normal conditions till being reloaded for 14 days. Compared with the control, RVIDd (diastolic RV internal diameter), and RV Vold (diastolic RV volume) were reduced in HU group and recovered to the normal conditions in HR-7d and HR-14d groups, in which groups RVIDs (systolic RV internal diameter) and RV Vols (systolic RV volume) were increased. Histological analysis and cardiac remodeling gene expression results indicated that HU induces left and right ventricular remodeling. Western blot demonstrated that the phosphorylation of HDAC4 and ERK1/2 and the ratio of LC3-II / LC3-I, were increased following HU and recovered following HR in both LV and RV, and the phosphorylation of AMPK was inhibited in both LV and RV following HU, but only restored in LV following HR for 14 days. These results indicate that simulated microgravity leads to cardiac remodeling, and the remodeling changes can

  9. Development of an automated processing method to detect still timing of cardiac motion for coronary magnetic resonance angiography

    Science.gov (United States)

    Asou, Hiroya; Ichikawa, Katsuhiro; Imada, Naoyuki; Masuda, Takanori; Satou, Tomoyasu

    2011-03-01

    Whole-heart coronary magnetic resonance angiography (WH-MRA) is useful noninvasive examination. Its signal acquisition is performed during very short still timing in each cardiac motion cycle, and therefore the adequate still timing selection is important to obtain the better image quality. However, since the current available selection method is only manual one using visual comparison of cine MRI images with different phases, the selected timings are often incorrect and their reproducibility is not sufficient. We developed an automated selection method to detect the best still timing for the WH-MRA and compared the automated method with conventional manual one. Cine MRI images were used for the analysis. In order to extract the high-speed cardiac cine image, each phase directional pixel set at each pixel position in all cine images were processed by a high-pass filtering using the Fourie transform. After this process, the cine images with low speed timing became dark, and the optimal timing could be determined by a threshold processing. We took ten volunteers' WH-MRA with the manually and automatically selected timings, and visually assessed image quality of each image on a 5-point scale (1=excellent, 2=very good, 3=good, 4=fair, 5=poor). The mean scores of the manual and automatic methods for right coronary arteries (RCA), LDA left anterior descending arteries (LAD) and LCX left circumflex arteries (LCX) were 4.2+/-0.38, 4.1+/-0.44, 3.9+/-0.52 and 4.1+/-0.42, 4.1+/-0.24, 3.2+/-0.35 respectively. The score were increased by our method in the RCA and LCX, and the LCX was significant (pcardiac phase more accurately than or equally to the conventional manual method.

  10. Remodeling of alveolar septa after murine pneumonectomy.

    Science.gov (United States)

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  11. Inhibition of CaMKII does not attenuate cardiac hypertrophy in mice with dysfunctional ryanodine receptor.

    Directory of Open Access Journals (Sweden)

    Asima Chakraborty

    Full Text Available In cardiac muscle, the release of calcium ions from the sarcoplasmic reticulum through ryanodine receptor ion channels (RyR2s leads to muscle contraction. RyR2 is negatively regulated by calmodulin (CaM and by phosphorylation of Ca2+/CaM-dependent protein kinase II (CaMKII. Substitution of three amino acid residues in the CaM binding domain of RyR2 (RyR2-W3587A/L3591D/F3603A, RyR2ADA impairs inhibition of RyR2 by CaM and results in cardiac hypertrophy and early death of mice carrying the RyR2ADA mutation. To test the cellular function of CaMKII in cardiac hypertrophy, mutant mice were crossed with mice expressing the CaMKII inhibitory AC3-I peptide or the control AC3-C peptide in the myocardium. Inhibition of CaMKII by AC3-I modestly reduced CaMKII-dependent phosphorylation of RyR2 at Ser-2815 and markedly reduced CaMKII-dependent phosphorylation of SERCA2a regulatory subunit phospholamban at Thr-17. However the average life span and heart-to-body weight ratio of Ryr2ADA/ADA mice expressing the inhibitory peptide were not altered compared to control mice. In Ryr2ADA/ADA homozygous mice, AC3-I did not alter cardiac morphology, enhance cardiac function, improve sarcoplasmic reticulum Ca2+ handling, or suppress the expression of genes implicated in cardiac remodeling. The results suggest that CaMKII was not required for the rapid development of cardiac hypertrophy in Ryr2ADA/ADA mice.

  12. A cardiac-specific health-related quality of life module for young adults with congenital heart disease: development and validation

    NARCIS (Netherlands)

    Kamphuis, M.; Zwinderman, K.A.H.; Vogels, T.; Vliegen, H.W.; Kamphuis, R.P.; Ottenkamp, J.; Verloove-Vanhorick, S.P.; Bruil, J.

    2004-01-01

    This study represents the development and validation of a cardiac-specific module of the generic health-related quality of life (HRQoL) instrument, the TAAQOL (TNO/AZL Adult Quality Of Life), for young adults with congenital heart disease (CHD). Items were selected based on literature, an explorativ

  13. Cardiac rehabilitation

    Science.gov (United States)

    ... attack or other heart problem. You might consider cardiac rehab if you have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery Heart transplant Procedures such as angioplasty and stenting In some ...

  14. Cardiac Rehabilitation

    Science.gov (United States)

    Cardiac rehabilitation (rehab) is a medically supervised program to help people who have A heart attack Angioplasty or coronary artery bypass grafting for coronary heart disease A heart valve repair or replacement A ...

  15. Assessment of cardiac sympathetic nerve integrity with positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Raffel, David M. E-mail: raffel@umich.edu; Wieland, Donald M

    2001-07-01

    The autonomic nervous system plays a critical role in the regulation of cardiac function. Abnormalities of cardiac innervation have been implicated in the pathophysiology of many heart diseases, including sudden cardiac death and congestive heart failure. In an effort to provide clinicians with the ability to regionally map cardiac innervation, several radiotracers for imaging cardiac sympathetic neurons have been developed. This paper reviews the development of neuronal imaging agents and discusses their emerging role in the noninvasive assessment of cardiac sympathetic innervation.

  16. Cardiac sarcoidosis

    OpenAIRE

    Costello BT; Nadel J.; Taylor AJ

    2016-01-01

    Benedict T Costello,1,2 James Nadel,3 Andrew J Taylor,1,21Department of Cardiovascular Medicine, The Alfred Hospital, 2Baker IDI Heart and Diabetes Research Institute, Melbourne, VIC, 3School of Medicine, University of Notre Dame, Sydney, NSW, Australia Abstract: Cardiac sarcoidosis is a rare but life-threatening condition, requiring a high degree of clinical suspicion and low threshold for investigation to make the diagnosis. The cardiac manifestations include heart failure, conducting syst...

  17. Asystole to cross-clamp period predicts development of biliary complications in liver transplantation using donation after cardiac death donors.

    Science.gov (United States)

    Taner, C Burcin; Bulatao, Ilynn G; Perry, Dana K; Sibulesky, Lena; Willingham, Darrin L; Kramer, David J; Nguyen, Justin H

    2012-08-01

    This study sought to determine the procurement factors that lead to development of intrahepatic bile duct strictures (ITBS) and overall biliary complications in recipients of donation after cardiac death (DCD) liver grafts. Detailed information for different time points during procurement (withdrawal of support; SBP mandatory wait period; asystole; incision; aortic cross clamp) and their association with the development of ITBS and overall biliary complications were examined using logistic regression. Two hundred and fifteen liver transplants using DCD donors were performed between 1998 and 2010 at Mayo Clinic Florida. Of all the time periods during procurement, only asystole-cross clamp period was significantly different between patients with ITBS versus no ITBS (P = 0.048) and between the patients who had overall biliary complications versus no biliary complications (P = 0.047). On multivariate analysis, only asystole-cross clamp period was significant predictor for development of ITBS (P = 0.015) and development of overall biliary complications (P = 0.029). Hemodynamic changes in the agonal period did not emerge as risk factors. The results of the study raise the possibility of utilizing asystole-cross-clamp period in place of or in conjunction with donor warm ischemia time in determining viability or quality of liver grafts. PMID:22703372

  18. Postmyocardial Infarct Remodeling and Heart Failure: Potential Contributions from Pro- and Antiaging Factors

    Directory of Open Access Journals (Sweden)

    Halliday A. Idikio

    2011-01-01

    Full Text Available Myocardial infarction and adverse postinfarct remodeling in older persons lead to poor outcome and need greater understanding of the contributions of age-related factors on abnormal cardiac function and management. In this perspective, how normal aging processes could contribute to the events of post-myocardial infarction and remodeling is reviewed. Post-myocardial infarction and remodeling involve cardiomechanical factors and neurohormonal response. Many factors prevent or accelerate aging including immunosenescence, recruitment and regeneration of stem cells, telomere shortening, oxidative damage, antiaging hormones klotho and melatonin, nutrition, and Sirtiun protein family, and these factors could affect post-MI remodeling and heart failure. Interest in stem cell repair of myocardial infarcts to mitigate post-MI remodeling needs more information on aging of stem cells, and potential effects on stem cell use in infarct repair. Integrating genomics and proteomics methods may help find clinically novel therapy in the management of post-MI remodeling and heart failure in aged individuals.

  19. A Metabolite-Sensitive, Thermodynamically Constrained Model of Cardiac Cross-Bridge Cycling: Implications for Force Development during Ischemia

    KAUST Repository

    Tran, Kenneth

    2010-01-01

    We present a metabolically regulated model of cardiac active force generation with which we investigate the effects of ischemia on maximum force production. Our model, based on a model of cross-bridge kinetics that was developed by others, reproduces many of the observed effects of MgATP, MgADP, Pi, and H(+) on force development while retaining the force/length/Ca(2+) properties of the original model. We introduce three new parameters to account for the competitive binding of H(+) to the Ca(2+) binding site on troponin C and the binding of MgADP within the cross-bridge cycle. These parameters, along with the Pi and H(+) regulatory steps within the cross-bridge cycle, were constrained using data from the literature and validated using a range of metabolic and sinusoidal length perturbation protocols. The placement of the MgADP binding step between two strongly-bound and force-generating states leads to the emergence of an unexpected effect on the force-MgADP curve, where the trend of the relationship (positive or negative) depends on the concentrations of the other metabolites and [H(+)]. The model is used to investigate the sensitivity of maximum force production to changes in metabolite concentrations during the development of ischemia.

  20. Cardiac image modelling: Breadth and depth in heart disease.

    Science.gov (United States)

    Suinesiaputra, Avan; McCulloch, Andrew D; Nash, Martyn P; Pontre, Beau; Young, Alistair A

    2016-10-01

    With the advent of large-scale imaging studies and big health data, and the corresponding growth in analytics, machine learning and computational image analysis methods, there are now exciting opportunities for deepening our understanding of the mechanisms and characteristics of heart disease. Two emerging fields are computational analysis of cardiac remodelling (shape and motion changes due to disease) and computational analysis of physiology and mechanics to estimate biophysical properties from non-invasive imaging. Many large cohort studies now underway around the world have been specifically designed based on non-invasive imaging technologies in order to gain new information about the development of heart disease from asymptomatic to clinical manifestations. These give an unprecedented breadth to the quantification of population variation and disease development. Also, for the individual patient, it is now possible to determine biophysical properties of myocardial tissue in health and disease by interpreting detailed imaging data using computational modelling. For these population and patient-specific computational modelling methods to develop further, we need open benchmarks for algorithm comparison and validation, open sharing of data and algorithms, and demonstration of clinical efficacy in patient management and care. The combination of population and patient-specific modelling will give new insights into the mechanisms of cardiac disease, in particular the development of heart failure, congenital heart disease, myocardial infarction, contractile dysfunction and diastolic dysfunction. PMID:27349830

  1. Chronic hypoxia inhibits MMP-2 activation and cellular invasion in human cardiac myofibroblasts

    OpenAIRE

    Riches, Kirsten; Morley, Michael E.; Turner, Neil A; O'Regan, David J; Ball, Stephen G; Peers, Chris; Porter, Karen E

    2009-01-01

    Cardiac myofibroblasts are pivotal to adaptive remodelling after myocardial infarction (MI). These normally quiescent cells invade and proliferate as a wound healing response, facilitated by activation of matrix metalloproteinases, particularly MMP-2. Following MI these reparative events occur under chronically hypoxic conditions yet the mechanisms by which hypoxia might modulate MMP-2 activation and cardiac myofibroblast invasion have not been investigated. Human cardiac myofibroblasts cultu...

  2. Maternal cardiac adaptations to a physical exercise program during pregnancy

    OpenAIRE

    Perales, María; Santos-Lozano, Alejandro; Sanchís-Gomar, Fabián; Luaces, María; Pareja Galeano, Helios; Garatachea, Nuria; Barakat, Rubén; Lucía Mulas, Alejandro

    2016-01-01

    INTRODUCTION: Scarce evidence exists regarding the effects of regular pregnancy exercise on maternal cardiovascular health. We aimed to study, using a randomized controlled trial design, the effects of pregnancy exercise on: echocardiographic indicators of hemodynamics, cardiac remodeling and left ventricular function, and cardiovascular disease (CVD) risk factors. METHODS: 241 healthy pregnant women were assigned to a control (standard care) or intervention (exercise) group (initi...

  3. Efficient computational simulation of actin stress fiber remodeling.

    Science.gov (United States)

    Ristori, T; Obbink-Huizer, C; Oomens, C W J; Baaijens, F P T; Loerakker, S

    2016-09-01

    Understanding collagen and stress fiber remodeling is essential for the development of engineered tissues with good functionality. These processes are complex, highly interrelated, and occur over different time scales. As a result, excessive computational costs are required to computationally predict the final organization of these fibers in response to dynamic mechanical conditions. In this study, an analytical approximation of a stress fiber remodeling evolution law was derived. A comparison of the developed technique with the direct numerical integration of the evolution law showed relatively small differences in results, and the proposed method is one to two orders of magnitude faster. PMID:26823159

  4. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Haipeng; Zhang, Xin [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Cui, Yuqian [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Zhou, Heng [Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan (China); Xu, Dachun [Department of Cardiology, Shanghai Tenth People' s Hospital of Tongji University, Shanghai (China); Shan, Tichao; Zhang, Fan [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Guo, Yuan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo, E-mail: chen919085@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wu, Dawei, E-mail: wdwu55@163.com [Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan (China); Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan (China)

    2015-09-01

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  5. Taxifolin protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload

    International Nuclear Information System (INIS)

    Cardiac hypertrophy is a key pathophysiological component to biomechanical stress, which has been considered to be an independent and predictive risk factor for adverse cardiovascular events. Taxifolin (TAX) is a typical plant flavonoid, which has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether TAX can influence the development of cardiac hypertrophy. In vitro studies, we found that TAX concentration-dependently inhibited angiotensin II (Ang II) induced hypertrophy and protein synthesis in cardiac myocytes. Then we established a mouse model by transverse aortic constriction (TAC) to further confirm our findings. It was demonstrated that TAX prevented pressure overload induced cardiac hypertrophy in mice, as assessed by ventricular mass/body weight, echocardiographic parameters, myocyte cross-sectional area, and the expression of ANP, BNP and β-MHC. The excess production of reactive oxygen species (ROS) played critical role in the development of cardiac hypertrophy. TAX arrested oxidative stress and decreased the expression of 4-HNE induced by pressure overload. Moreover, TAX negatively modulated TAC-induced phosphorylation of ERK1/2 and JNK1/2. Further studies showed that TAX significantly attenuated left ventricular fibrosis and collagen synthesis through abrogating the phosphorylation of Smad2 and Smad2/3 nuclear translocation. These results demonstrated that TAX could inhibit cardiac hypertrophy and attenuate ventricular fibrosis after pressure overload. These beneficial effects were at least through the inhibition of the excess production of ROS, ERK1/2, JNK1/2 and Smad signaling pathways. Therefore, TAX might be a potential candidate for the treatment of cardiac hypertrophy and fibrosis. - Highlights: • We focus on the protective effect of taxifolin on cardiac remodeling. • Taxifolin inhibited cardiac hypertrophy and attenuated ventricular fibrosis. • Taxifolin

  6. PARP inhibition and postinfarction myocardial remodeling.

    Science.gov (United States)

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  7. Effect of melatonin, captopril, spironolactone and simvastatin on blood pressure and left ventricular remodelling in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Šimko, F.; Pecháňová, Olga; Pelouch, Václav; Krajčírovičová, K.; Müllerová, M.; Bednárová, K.; Adamcová, M.; Paulis, L.

    2009-01-01

    Roč. 27, Suppl.6 (2009), S5-S10. ISSN 0263-6352 R&D Projects: GA ČR GA305/09/0336 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac hypertrophy * fibrosis * ventricular remodeling Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.988, year: 2009

  8. Left ventricular structure and remodeling in patients with COPD

    Science.gov (United States)

    Pelà, Giovanna; Li Calzi, Mauro; Pinelli, Silvana; Andreoli, Roberta; Sverzellati, Nicola; Bertorelli, Giuseppina; Goldoni, Matteo; Chetta, Alfredo

    2016-01-01

    Background Data on cardiac alterations such as left ventricular (LV) hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features. Methods Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score. Results Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT), suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42) predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81). Patients with COPD showed right ventricular to be functional but no structural changes. Conclusion Patients with COPD without evident cardiovascular disease exhibit significant changes in LV geometry, resulting in concentric remodeling. In all individuals, RWT was significantly and independently related to COPD. However, its prognostic role should be determined in future studies. PMID:27257378

  9. The Cardiac Ventricular 5-HT4 Receptor Is Functional in Late Foetal Development and Is Reactivated in Heart Failure

    OpenAIRE

    Brattelid, Trond; Qvigstad, Eirik; Moltzau, Lise R; Bekkevold, Silje V. S.; Sandnes, Dagny L; Birkeland, Jon Arne K.; Skomedal, Tor; Osnes, Jan-Bjørn; Sjaastad, Ivar; Levy, Finn Olav

    2012-01-01

    A positive inotropic responsiveness to serotonin, mediated by 5-HT4 and 5-HT2A receptors, appears in the ventricle of rats with post-infarction congestive heart failure (HF) and pressure overload-induced hypertrophy. A hallmark of HF is a transition towards a foetal genotype which correlates with loss of cardiac functions. Thus, we wanted to investigate whether the foetal and neonatal cardiac ventricle displays serotonin responsiveness. Wistar rat hearts were collected day 3 and 1 before expe...

  10. Predictors and long-term clinical outcomes of newly developed atrial fibrillation in patients with cardiac implantable electronic devices

    Science.gov (United States)

    Kim, Bum Sung; Chun, Kwang Jin; Hwang, Jin kyung; Park, Seung-Jung; Park, Kyoung-Min; Kim, June Soo; On, Young Keun

    2016-01-01

    Abstract Objective: To evaluate predictors and long-term prognosis of atrial fibrillation (AF) following cardiac implantable electronic device (CIED) implantation in patients without history of AF. Methods: From May 1994 to April 2014, 1825 patients with CIED were enrolled in a retrospective, single-center registry. A total of 880 patients from the registry without prior documented AF history were included in the final analysis and were placed into either non-detected AF (NDAF) group or CIED-detected AF group according to development of AF over a follow-up period of 7 years. AF development was defined as any paroxysmal atrial tachyarrhythmia (atrial rate ≥ 180 beats/min) lasting at least 5 minutes according to CIED records. Results: Overall, 122 (13.8%) of the 880 patients experienced new development of AF during follow-up period. According to multivariate analysis, the independent predictors for development of AF were prior heart failure (hazard ratio [HR], 2.40; 95% confidence interval [CI], 1.50–3.85; P HR, 2.33; 95% CI, 1.62–3.55; P HR, 2.01; 95% CI, 1.23–3.30; P = 0.005). In CDAF group, the risk of heart failure readmission (adjusted HR, 3.79; 95% CI, 1.99–7.22; P HR, 5.33; 95% CI, 1.58–17.97; P = 0.007) was higher than in nondetected AF group. Conclusion: In patients with CIED, prior history of heart failure, sinus node dysfunction, and LA volume index ≥38.5 mL/m2 were independent predictors of new AF cases. Newly developed AF was significantly associated with increased risk of HF and stroke readmission, according to long-term follow up. PMID:27428213

  11. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  12. Cardiac CT

    Energy Technology Data Exchange (ETDEWEB)

    Dewey, Marc [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie

    2011-07-01

    Computed tomography of the heart has become a highly accurate diagnostic modality that is attracting increasing attention. This extensively illustrated book aims to assist the reader in integrating cardiac CT into daily clinical practice, while also reviewing its current technical status and applications. Clear guidance is provided on the performance and interpretation of imaging using the latest technology, which offers greater coverage, better spatial resolution, and faster imaging. The specific features of scanners from all four main vendors, including those that have only recently become available, are presented. Among the wide range of applications and issues to be discussed are coronary artery bypass grafts, stents, plaques, and anomalies, cardiac valves, congenital and acquired heart disease, and radiation exposure. Upcoming clinical uses of cardiac CT, such as plaque imaging and functional assessment, are also explored. (orig.)

  13. Cardiac echinococcosis

    Directory of Open Access Journals (Sweden)

    Ivanović-Krstić Branislava A.

    2002-01-01

    Full Text Available Cardiac hydatid disease is rare. We report on an uncommon hydatid cyst localized in the right ventricular wall, right atrial wall tricuspid valve left atrium and pericard. A 33-year-old woman was treated for cough, fever and chest pain. Cardiac echocardiograpic examination revealed a round tumor (5.8 x 4 cm in the right ventricular free wall and two smaller cysts behind that tumor. There were cysts in right atrial wall and tricuspidal valve as well. Serologic tests for hydatidosis were positive. Computed tomography finding was consistent with diagnosis of hydatid cyst in lungs and right hylar part. Surgical treatment was rejected due to great risk of cardiac perforation. Medical treatment with albendazole was unsuccessful and the patient died due to systemic hydatid involvement of the lungs, liver and central nervous system.

  14. SIGNALLING THROUGH RETINOIC ACID RECEPTORS IN CARDIAC DEVELOPMENT: DOING THE RIGHT THINGS AT THE RIGHT TIMES

    OpenAIRE

    Xavier-Neto, José; Costa, Ângela M. Sousa; Figueira, Ana Carolina M.; Caiaffa, Carlo Donato; do Amaral, Fabio Neves; Peres, Lara Maldanis Cerqueira; da Silva, Bárbara Santos Pires; Santos, Luana Nunes; Moise, Alexander R.; Castillo, Hozana Andrade

    2014-01-01

    Retinoic acid (RA) is a terpenoid that is synthesized from Vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinic and experimental data provide uncontested evidence for the pleiotropic roles of RA signalling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of thes...

  15. Strategies for the improvement of cardiac care services in developing countries: what does the future hold?

    Science.gov (United States)

    Saxena, Anita

    2012-01-01

    Cardiovascular disease is the leading cause of death in developing countries. The atherosclerotic or degenerative diseases are not only on the rise, they are occurring at a younger age compared with those in developed nations. Some of these developing countries continue to have a high prevalence of rheumatic heart disease, with a large number of new cases with acute rheumatic fever. It appears that the prevalence of congenital heart disease has remained the same in both developing and developed countries, although the actual data are missing. Most of the developing countries have an increasing population due to high birth rate thereby the burden of all types of cardiovascular disease is increasing. Unfortunately, a majority of the patients with cardiovascular disease do not get appropriate and timely care. The health system in most of these countries is very heterogeneous and hospital based, often catering only to the urban population. Although private healthcare is available in some regions, it is unaffordable for the majority. The current situation needs urgent action for control of the impending cardiovascular disease epidemic and for improving the care of the affected population. The first aspect for improvement is generation of relevant data regarding the actual burden, risk factors, morbidity and mortality. Other strategies include policy interventions for the control of risk factors in the community, raising public awareness about the various cardiovascular diseases and building research capacity. The resources are not only limited, but are improperly utilized. PMID:22185444

  16. Cardiac sarcoidosis

    Science.gov (United States)

    Smedema, J.P.; Zondervan, P.E.; van Hagen, P.; ten Cate, F.J.; Bresser, P.; Doubell, A.F.; Pattynama, P.; Hoogsteden, H.C.; Balk, A.H.M.M.

    2002-01-01

    Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696121

  17. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Science.gov (United States)

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (Phospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.

  18. The Metal Chelators, Trientine and Citrate, Inhibit the Development of Cardiac Pathology in the Zucker Diabetic Rat

    Directory of Open Access Journals (Sweden)

    John W. Baynes

    2009-01-01

    Full Text Available Purpose. The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. Hypothesis. We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricular structure and function in type II diabetes. Methods. Animals (10 weeks old included lean control (LC, fa/+, untreated Zucker diabetic fatty (ZDF, fa/fa, and ZDF rats treated with either trientine (triethylenetetramine or citrate at 20 mg/d in drinking water, starting when rats were frankly diabetic. Cardiac functional assessment was determined using a Millar pressure/volume catheter placed in the left ventricle at 32 weeks of age. Results. End diastolic volume for the ZDF animals increased by 36% indicating LV dilatation (P<.05 and was accompanied by a 30% increase in the end diastolic pressure (P≤.05. Both trientine and citric acid prevented the increases in EDV and EDP (P<.05. Ejection fraction and myocardial relaxation were also significantly improved with chelator treatment. Conclusion. Dietary supplementation with trientine and citric acid significantly prevented structural and functional changes in the diabetic heart, supporting the merits of mild chelators for prevention of cardiovascular disease in diabetes.

  19. Synapse formation and remodeling

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Synapses are specialized structures that mediate information flow between neurons and target cells,and thus are the basis for neuronal system to execute various functions,including learning and memory.There are around 1011 neurons in the human brain,with each neuron receiving thousands of synaptic inputs,either excitatory or inhibitory.A synapse is an asymmetric structure that is composed of pre-synaptic axon terminals,synaptic cleft,and postsynaptic compartments.Synapse formation involves a number of cell adhesion molecules,extracellular factors,and intracellular signaling or structural proteins.After the establishment of synaptic connections,synapses undergo structural or functional changes,known as synaptic plasticity which is believed to be regulated by neuronal activity and a variety of secreted factors.This review summarizes recent progress in the field of synapse development,with particular emphasis on the work carried out in China during the past 10 years(1999-2009).

  20. Regulation of Cardiac Hypertrophy: the nuclear option

    OpenAIRE

    Kuster, Diederik

    2011-01-01

    textabstractCardiac hypertrophy is the response of the heart to an increased workload. After myocardial infarction (MI) the surviving muscle tissue has to work harder to maintain cardiac output. This sustained increase in workload leads to cardiac hypertrophy. Despite its apparent appropriateness, cardiac hypertrophy is an independent risk factor for the development of heart failure and is therefore called pathological hypertrophy. That hypertrophy is not bad per se, is illustrated by the hyp...

  1. Traumatic Tricuspid Regurgitation Following Cardiac Massage

    OpenAIRE

    Na, Sungwon; Nam, Sang Beom; Lee, Yong Kyung; Oh, Young Jun; Kwak, Young-Lan

    2007-01-01

    We report a 66-yr-old male patient who developed tricuspid regurgitation secondary to internal cardiac massage. After uneventful off-pump coronary artery bypass surgery, the subject experienced cardiac arrest in the intensive care unit. External cardiac massage was initiated and internal cardiac massage was performed eventually. A transesophageal echocardiography revealed avulsion of the anterior papillary muscle and chordae to the anterior leaflet after successful cardiopulmonary resuscitati...

  2. Blood-borne stem cells differentiate into vascular and cardiac lineages during normal development

    Czech Academy of Sciences Publication Activity Database

    Zhang, N.; Mustin, D.; Reardon, M. W.; Dealmeida, A.; Mozdziak, P.; Mrug, M.; Eisenberg, L. M.; Sedmera, David

    2006-01-01

    Roč. 15, 1 (2006), s. 17-28. ISSN 1547-3287 Grant ostatní: March of Dimes 5-FY02-269; NIH RR16434 Institutional research plan: CEZ:AV0Z50450515 Keywords : stem cells * embryonic development * circulation Subject RIV: EA - Cell Biology Impact factor: 3.076, year: 2006

  3. Development of a Squamous Cell Carcinoma of the Hand and Wrist After Cardiac Transplantation.

    Science.gov (United States)

    Carey, Sandra; Jackson, Warren T; Hitchcock, Michael A; Lima, Brian; Hall, Shelley

    2016-06-01

    Described are the findings in a 57-year-old man who developed a large carcinoma 2 years after heart transplantation. Mental anxiety or depression may have contributed to a delay in seeking medical care. The result was amputation of the right arm below the elbow. PMID:27084051

  4. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

    OpenAIRE

    Gomez, Juan F.; Cardona, Karen; Martinez, Laura; Saiz, Javier; Trenor, Beatriz

    2014-01-01

    Background Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established electrophysiolog...

  5. Arrhythmogenic remodelling of activation and repolarization in the failing human heart

    OpenAIRE

    Holzem, Katherine M.; Efimov, Igor R.

    2012-01-01

    Heart failure is a major cause of disability and death worldwide, and approximately half of heart failure-related deaths are sudden and presumably due to ventricular arrhythmias. Patients with heart failure have been shown to be at 6- to 9-fold increased risk of sudden cardiac death compared to the general population. (AHA. Heart Disease and Stroke Statistics—2003 Update. Heart and Stroke Facts. Dallas, TX: American Heart Association; 2002) Thus, electrophysiological remodelling associated wi...

  6. Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study

    OpenAIRE

    Gómez García, Juan Francisco; Saiz Rodríguez, Francisco Javier; Trenor Gomis, Beatriz Ana

    2014-01-01

    Background: Heart failure is operationally defined as the inability of the heart to maintain blood flow to meet the needs of the body and it is the final common pathway of various cardiac pathologies. Electrophysiological remodeling, intercellular uncoupling and a pro-fibrotic response have been identified as major arrhythmogenic factors in heart failure. Objective: In this study we investigate vulnerability to reentry under heart failure conditions by incorporating established ...

  7. Molecular pathogenesis of myocardial remodeling and new potential therapeutic targets in chronic heart failure

    OpenAIRE

    Distefano Giuseppe; Sciacca Pietro

    2012-01-01

    Abstract It is well known that the natural history of chronic heart failure (CHF),regardless of age and aetiology,is characterized by progressive cardiac dysfunction refractory to conventional cardiokinetic, diuretic and peripheral vasodilator therapy. Several previous studies, both in animals and humans, showed that the key pathogenetic element of CHF negative clinical evolution is constituted by myocardial remodeling. This is a complex pathologic process of ultrastructural rearrangement of ...

  8. Development of a sensitive immunosensor for the detection of cardiac Troponin T in cardiovascular disease

    OpenAIRE

    Pawula, Maria

    2014-01-01

    Cardiovascular disease (CVD) is currently globally the biggest cause of mortality, with rising figures, especially now in the developing world. Early and accurate diagnosis of CVD, (especially acute myocardial infarction (AMI) is important in being able to provide appropriate, timely and cost effective treatment, or to take preventative action. Biomarkers and biosensors are playing an increasingly important role in this diagnosis, especially those based on immunoassays. As technology improves...

  9. Problems encountered during the development and implantation of the Baylor-Rice orthotopic cardiac prosthesis

    International Nuclear Information System (INIS)

    The problems associated with the development of an artificial heart are enumerated. In a series of 24 calf implantations, several of the animals stood unassisted and reacted normally, but all eventually died with deteriorating circulatory and pulmonary systems. The problems caused by pump size and geometry represented the most important deterrents to long-term survival. A new prosthesis, though not yet tested in animals, is believed to minimize these problems. (auth)

  10. Cardiac expression patterns of endothelin-converting enzyme (ECE): Implications for conduction system development

    Czech Academy of Sciences Publication Activity Database

    Sedmera, David; Harris, B. S.; Grant, E.; Zhang, N.; Jourdan, J.; Kurková, D.; Gourdie, R. G.

    2008-01-01

    Roč. 237, - (2008), s. 1746-1753. ISSN 1058-8388 R&D Projects: GA ČR GA304/08/0615 Grant ostatní: AV ČR(CZ) Purkyně Fellowship Institutional research plan: CEZ:AV0Z50450515 Keywords : chick embryo * heart development * immunohistochemistry Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.018, year: 2008

  11. Histamine in regulation of bone remodeling processes

    Directory of Open Access Journals (Sweden)

    Marek Wiercigroch

    2013-08-01

    Full Text Available Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H1 receptor antagonists are widely used in the treatment of allergic conditions, H2 receptor antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist and H1 receptor agonist is used in the treatment of Ménière’s disease.Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results.Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts. Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and H2 receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed.

  12. [Histamine in regulation of bone remodeling processes].

    Science.gov (United States)

    Wiercigroch, Marek; Folwarczna, Joanna

    2013-01-01

    Bone remodeling is under autocrine, paracrine, endocrine and central nervous system control. One of the potential endogenous factors affecting bone remodeling is histamine, an endogenous amine which acts as a mediator of allergic reactions and neuromediator, and induces production of gastric acid. Histamine H₁ receptor antagonists are widely used in the treatment of allergic conditions, H₂ receptor antagonists in peptic ulcer disease, and betahistine (an H₃ receptor antagonist and H₁ receptor agonist) is used in the treatment of Ménière's disease. Excess histamine release in mastocytosis and allergic diseases may lead to development of osteoporosis. Clinical and population-based studies on the effects of histamine receptor antagonists on the skeletal system have not delivered unequivocal results. Expression of mRNA of histamine receptors has been discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has been demonstrated in osteoclast precursors. Histamine increases bone resorption both by direct effects on osteoclast precursors and osteoclasts, and indirectly, by increasing the expression of RANKL in osteoblasts. In in vivo studies, H₁ and H₂ receptor antagonists exerted protective effects on the bone tissue, although not in all experimental models. In the present article, in vitro and in vivo studies conducted so far, concerning the effects of histamine and drugs modifying its activity on the skeletal system, have been reviewed. PMID:24018454

  13. Optimizing preoperative expectations in cardiac surgery patients is moderated by level of disability: the successful development of a brief psychological intervention.

    Science.gov (United States)

    Laferton, Johannes A C; Auer, Charlotte J; Shedden-Mora, Meike C; Moosdorf, Rainer; Rief, Winfried

    2016-04-01

    Patients' expectations have shown to be a major psychological predictor of health outcome in cardiac surgery patients. However, it is unclear whether patients' expectations can be optimized prior to surgery. This study evaluates the development of a brief psychological intervention focusing on the optimization of expectations and its effect on change in patients' expectations prior to cardiac surgery. Ninety patients scheduled for coronary artery bypass graft were randomly assigned to (1) standard medical care, (2) additional expectation manipulation intervention (EMI), and (3) additional attention control group. Therapists' fidelity to intervention manuals and patients satisfaction with the intervention were assessed for both active intervention conditions. Patients' expectations about post-surgical disability, treatment control, personal control, and disease duration were assessed before and after the psychological intervention. Demographical, medical, and psychosocial characteristics and disability were assessed at baseline. Treatment fidelity and patient satisfaction was very high in both intervention conditions. Only patients receiving EMI developed higher personal control expectations and longer (more realistic) expectations of disease duration. The effect of intervention group on patients' disability expectations and patients' personal control expectations was moderated by patient's level of disability. EMI patients with low to moderate disability developed positive expectations whereas patients with high disability did not. This study shows the successful development of a short psychological intervention that was able to modify patients' expectations, especially in those with low to moderate disability. Given the robust association of expectations and surgery outcome, such an intervention might offer the opportunity to enhance patients' health following cardiac surgery. PMID:26042657

  14. Left ventricular structure and remodeling in patients with COPD

    Directory of Open Access Journals (Sweden)

    Pelà G

    2016-05-01

    Full Text Available Giovanna Pelà,1 Mauro Li Calzi,1 Silvana Pinelli,1 Roberta Andreoli,1 Nicola Sverzellati,2 Giuseppina Bertorelli,1 Matteo Goldoni,1 Alfredo Chetta11Department of Clinical and Experimental Medicine, 2Department of Surgery, University Medical School, University Hospital Parma, Parma, ItalyBackground: Data on cardiac alterations such as left ventricular (LV hypertrophy, diastolic dysfunction, and lower stroke volume in patients with COPD are discordant. In this study, we investigated whether early structural and functional cardiac changes occur in patients with COPD devoid of manifest cardiovascular disease, and we assessed their associations with clinical and functional features.Methods: Forty-nine patients with COPD belonging to all Global Initiative for Chronic Obstructive Lung Disease (GOLD classes were enrolled and compared with 36 controls. All subjects underwent clinical history assessment, lung function testing, blood pressure measurement, electrocardiography, and conventional and Doppler tissue echocardiography. Patients were also subjected to computed tomography to quantify emphysema score.Results: Patients with COPD had lower LV cavity associated with a marked increase in relative wall thickness (RWT, suggesting concentric remodeling without significant changes in LV mass. RWT was significantly associated with ratio of the forced expiratory volume in 1 second to the forced vital capacity and emphysema score and was the only cardiac parameter that – after multivariate analysis – significantly correlated with COPD conditions in all individuals. Receiver operating characteristic curve analysis showed that RWT (with a cutoff point of 0.42 predicted the severity of COPD with 83% specificity and 56% sensitivity (area under the curve =0.69, 95% confidence interval =0.59–0.81. Patients with COPD showed right ventricular to be functional but no structural changes.Conclusion: Patients with COPD without evident cardiovascular disease

  15. Cerebral Salt Wasting Syndrome After Calvarial Remodeling in Craniosynostosis

    OpenAIRE

    Byeon, Jun-Hee; Yoo, Gyeol

    2005-01-01

    Hyponatremia and increased urine output after calvarial remodeling have been noted in pediatric patients with craniosynostosis. If not treated properly, patients develop hypoosmotic conditions that can lead to cerebral edema, increased intracranial pressure, and collapsed circulation. Postoperative hyponatremia after central nervous system surgery is considered as the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recently, however, cerebral salt wasting syndrome (CSWS) ins...

  16. Remodeling in asthma and chronic obstructive pulmonary disease

    NARCIS (Netherlands)

    Postma, Dirkje S; Timens, Wim

    2006-01-01

    Airway and lung tissue remodeling and fibrosis play an important role in the development of symptoms associated with lung function loss in asthma and chronic obstructive pulmonary disease (COPD). In the past decades, much attention has been paid to the inflammatory cellular process involved in airwa

  17. Intraoperative PaO2 is not related to the development of surgical site infections after major cardiac surgery

    Directory of Open Access Journals (Sweden)

    Fierro Inma

    2011-01-01

    Full Text Available Abstract Background The perioperative use of high inspired oxygen fraction (FIO2 for preventing surgical site infections (SSIs has demonstrated a reduction in their incidence in some types of surgery however there exist some discrepancies in this respect. The aim of this study was to analyze the relationship between PaO2 values and SSIs in cardiac patients. Methods We designed a prospective study in which 1,024 patients undergoing cardiac surgery were analyzed. Results SSIs were observed in 5.3% of patients. There was not significant difference in mortality at 30 days between patients with and without SSIs. In the uni and multivariate analysis no differences in function of the inspired oxygen fraction administrated were observed. Conclusions We observed that the PaO2 in adult cardiac surgery patients was not related to SSI rate.

  18. Cellular and Molecular Mechanisms of Bone Remodeling*

    OpenAIRE

    Raggatt, Liza J; Partridge, Nicola C

    2010-01-01

    Physiological bone remodeling is a highly coordinated process responsible for bone resorption and formation and is necessary to repair damaged bone and to maintain mineral homeostasis. In addition to the traditional bone cells (osteoclasts, osteoblasts, and osteocytes) that are necessary for bone remodeling, several immune cells have also been implicated in bone disease. This minireview discusses physiological bone remodeling, outlining the traditional bone biology dogma in light of emerging ...

  19. An overview of cardiac morphogenesis.

    OpenAIRE

    Schleich, Jean-Marc; Abdulla, Tariq; Summers, Ron; Houyel, Lucile

    2013-01-01

    International audience Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In th...

  20. Development of antibody-siRNA conjugate targeted to cardiac and skeletal muscles.

    Science.gov (United States)

    Sugo, Tsukasa; Terada, Michiko; Oikawa, Tatsuo; Miyata, Kenichi; Nishimura, Satoshi; Kenjo, Eriya; Ogasawara-Shimizu, Mari; Makita, Yukimasa; Imaichi, Sachiko; Murata, Shumpei; Otake, Kentaro; Kikuchi, Kuniko; Teratani, Mika; Masuda, Yasushi; Kamei, Takayuki; Takagahara, Shuichi; Ikeda, Shota; Ohtaki, Tetsuya; Matsumoto, Hirokazu

    2016-09-10

    Despite considerable efforts to develop efficient carriers, the major target organ of short-interfering RNAs (siRNAs) remains limited to the liver. Expanding the application outside the liver is required to increase the value of siRNAs. Here we report on a novel platform targeted to muscular organs by conjugation of siRNAs with anti-CD71 Fab' fragment. This conjugate showed durable gene-silencing in the heart and skeletal muscle for one month after intravenous administration in normal mice. In particular, 1μg siRNA conjugate showed significant gene-silencing in the gastrocnemius when injected intramuscularly. In a mouse model of peripheral artery disease, the treatment with myostatin-targeting siRNA conjugate by intramuscular injection resulted in significant silencing of myostatin and hypertrophy of the gastrocnemius, which was translated into the recovery of running performance. These data demonstrate the utility of antibody conjugation for siRNA delivery and the therapeutic potential for muscular diseases. PMID:27369865

  1. The development and initial evaluation of a realistic simulated SPECT dataset with simultaneous respiratory and cardiac motion for gated myocardial perfusion SPECT

    Science.gov (United States)

    Lee, Taek-Soo; Tsui, Benjamin M. W.

    2015-02-01

    We developed a realistic simulation dataset for simultaneous respiratory and cardiac (R&C) gated SPECT/CT using the 4D NURBS-based Cardiac-Torso (NCAT) Phantom and Monte Carlo simulation methods, and evaluated it for a sample application study. The 4D NCAT phantom included realistic respiratory motion and beating heart motion based on respiratory gated CT and cardiac tagged MRI data of normal human subjects. To model the respiratory motion, a set of 24 separate 3D NCAT phantoms excluding the heart was generated over a respiratory cycle. The beating heart motion was modeled separately with 48 frames per cardiac cycle for each of the 24 respiratory phases. The resultant set of 24  ×  48 3D NCAT phantoms provides a realistic model of a normal human subject at different phases of combined R&C motions. An almost noise-free SPECT projection dataset for each of the 1152 3D NCAT phantoms was generated using Monte Carlo simulation techniques and the radioactivity uptake distribution of 99mTc sestamibi in different organs. By grouping and summing the separate projection datasets, separate or simultaneous R&C gated acquired data with different gating schemes could be simulated. In the initial evaluation, we combined the projection datasets into ungated, 6 respiratory-gates only, 8 cardiac-gates only, and combined 6 respiratory-gates & 8 cardiac-gates projection datasets. Each dataset was reconstructed using 3D OS-EM without and with attenuation correction using the averaged and respiratory-gated attenuation maps, and the resulting reconstructed images were compared. These results were used to demonstrate the effects of R&C motions and the reduction of image artifact due to R&C motions by gating and attenuation corrections. We concluded that the realistic 4D NCAT phantom and Monte Carlo simulated SPECT projection datasets with R&C motions are powerful tools in the study of the effects of R&C motions, as well as in the development of R&C gating schemes and motion

  2. The development and initial evaluation of a realistic simulated SPECT dataset with simultaneous respiratory and cardiac motion for gated myocardial perfusion SPECT

    International Nuclear Information System (INIS)

    We developed a realistic simulation dataset for simultaneous respiratory and cardiac (R and C) gated SPECT/CT using the 4D NURBS-based Cardiac-Torso (NCAT) Phantom and Monte Carlo simulation methods, and evaluated it for a sample application study. The 4D NCAT phantom included realistic respiratory motion and beating heart motion based on respiratory gated CT and cardiac tagged MRI data of normal human subjects. To model the respiratory motion, a set of 24 separate 3D NCAT phantoms excluding the heart was generated over a respiratory cycle. The beating heart motion was modeled separately with 48 frames per cardiac cycle for each of the 24 respiratory phases. The resultant set of 24  ×  48 3D NCAT phantoms provides a realistic model of a normal human subject at different phases of combined R and C motions. An almost noise-free SPECT projection dataset for each of the 1152 3D NCAT phantoms was generated using Monte Carlo simulation techniques and the radioactivity uptake distribution of 99mTc sestamibi in different organs. By grouping and summing the separate projection datasets, separate or simultaneous R and C gated acquired data with different gating schemes could be simulated. In the initial evaluation, we combined the projection datasets into ungated, 6 respiratory-gates only, 8 cardiac-gates only, and combined 6 respiratory-gates and 8 cardiac-gates projection datasets. Each dataset was reconstructed using 3D OS-EM without and with attenuation correction using the averaged and respiratory-gated attenuation maps, and the resulting reconstructed images were compared. These results were used to demonstrate the effects of R and C motions and the reduction of image artifact due to R and C motions by gating and attenuation corrections. We concluded that the realistic 4D NCAT phantom and Monte Carlo simulated SPECT projection datasets with R and C motions are powerful tools in the study of the effects of R and C motions, as well as in the development of R and C

  3. Atrial tumors in cardiac MRI

    International Nuclear Information System (INIS)

    Cardiac magnetic resonance imaging (MRI) is an important tool for the diagnosis of cardiac masses. Various cardiac tumors are predisposed to occurring in atrial structures. The aim of this review article is the description of atrial tumors and their morphological features in MRI. In general, cardiac tumors are rare: approximately 0.001-0.03% in autopsy studies. About 75% of them are benign. The most common cardiac tumor is the myxoma. They are predisposed to occur in the atria and show a characteristically strong hyperintense signal on T2-wieghted images in MRI. In other sequences a heterogeneous pattern reflects its variable histological appearance. Lipomas exhibit a signal behavior identical to fatty tissue with a typical passive movement in cine imaging. Fibroelastomas are the most common tumors of the cardiac valves. Consisting of avascular fibrous tissue, they often present with hypointense signal intensities. Thrombi attached to their surface can cause severe emboli even in small tumors. Amongst primary cardiac malignancies, sarcomas are most common and favor the atria. Secondary malignancies of the heart are far more common than primary ones (20-40 times). In case of known malignancies, approximately 10% of patients develop cardiac metastasis at the end of their disease. Lymphogenic metastases favor the pericardium, while hematogenic spread prefers the myocardium. Since they are not real atrial tumors, thrombi and anatomical structures of the atria have to be differentiated from other pathologies. (orig.)

  4. Molecular and cellular neurocardiology: development, and cellular and molecular adaptations to heart disease.

    Science.gov (United States)

    Habecker, Beth A; Anderson, Mark E; Birren, Susan J; Fukuda, Keiichi; Herring, Neil; Hoover, Donald B; Kanazawa, Hideaki; Paterson, David J; Ripplinger, Crystal M

    2016-07-15

    The nervous system and cardiovascular system develop in concert and are functionally interconnected in both health and disease. This white paper focuses on the cellular and molecular mechanisms that underlie neural-cardiac interactions during development, during normal physiological function in the mature system, and during pathological remodelling in cardiovascular disease. The content on each subject was contributed by experts, and we hope that this will provide a useful resource for newcomers to neurocardiology as well as aficionados. PMID:27060296

  5. Preliminary studies of Technetium-99m-labeled antimyosin monoclonal antibody: development of radiopharmaceutical for cardiac evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Guilherme Luiz de Castro; Spencer, Patrick Jack; Muramoto, Emiko; Araujo, Elaine Bortoleti de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: glcarval@ipen.br

    2007-07-01

    In the acute myocardium infarction, the myocytes cell membrane loses its integrity, allowing the influx of extracellular macromolecules such as circulating antibody into the damaged cell. Specific antibodies to cardiac myosin can therefore bind to the acutely necrotic myocyte, allowing the noninvasive localization and dimension of myocardial infarction. Because of its favorable physical characteristics, low cost, and ready availability, technetium-99m ({sup 99m}Tc) is the radionuclide of choice for scintigraphy. The purpose of this work was to study the labeling of the antimyosin monoclonal antibody with ({sup 99m}Tc for development of a radiopharmaceutical with high sensitivity and specificity used in the diagnostic of the myocardial infarction. The intact monoclonal antibody (IgG{sub 1}) was reduced by treatment with dithiothreitol (DTT) with the consequent generation of free thiol groups (- SH), responsible for the labeling of the antibody with ({sup 99m}Tc. The radiochemical yield was determined using Sephadex G-25 column (PD-10). The percentage of ({sup 99m}Tc-antibody was 90,06% and after purification procedure the radiochemical yield was > 98%. The biodistribution studies showed low uptake in the stomach and thyroid at different times (1, 4 e 24 hours) representing a small amount of unbounded ({sup 99m}Tc and a good stability of the purified ({sup 99m}Tc-antibody. The uptake in the normal heart was relatively low as expected. Based on these results, we concluded that the direct labeling procedure applied to the antimyosin monoclonal antibody allowed the easy preparation of the radiopharmaceutical with good stability to be used in the noninvasive diagnostic of the myocardial infarction. (author)

  6. Valsartan Reduced Atrial Fibrillation Susceptibility by Inhibiting Atrial Parasympathetic Remodeling through MAPKs/Neurturin Pathway

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2015-07-01

    Full Text Available Background/Aims: Angiotensin II receptor blockers (ARBs have been proved to be effective in preventing atrial structural and electrical remodelinq in atrial fibrillation (AF. Previous studies have shown that parasympathetic remodeling plays an important role in AF. However, the effects of ARBs on atrial parasympathetic remodeling in AF and the underlying mechanisms are still unknown. Methods: Canines were divided into sham-operated, pacing and valsartan + pacing groups. Rats and HL-1 cardiomyocytes were divided into control, angiotensin II (Ang II and Ang II + valsartan groups, respectively. Atrial parasympathetic remodeling was quantified by immunocytochemical staining with anti-choline acetyltransferase (ChAT antibody. Western blot was used to analysis the protein expression of neurturin. Results: Both inducibility and duration were increased in chronic atrial rapid-pacing canine model, which was significantly inhibited by the treatment with valsartan. The density of ChAT-positive nerves and the protein level of neurturin in the atria of pacing canines were both increased than those in sham-operated canines. Ang II treatment not only induced atrial parasympathetic remodeling in rats, but also up-regulated the protein expression of neurturin. Valsartan significantly prevented atrial parasympathetic remodeling, and suppressed the protein expression of neurturin. Meanwhile, valsartan inhibited Ang II -induced up-regulation of neurturin and MAPKs in cultured cardiac myocytes. Inhibition of MAPKs dramatically attenuated neurturin up-regulation induced by Ang II. Conclusion: Parasympathetic remodeling was present in animals subjected to rapid pacing or Ang II infusion, which was mediated by MAPKs/neurturin pathway. Valsartan is able to prevent atrial parasympathetic remodeling and the occurrence of AF via inhibiting MAPKs/neurturin pathway.

  7. Inhibition of miR-15 Protects Against Cardiac Ischemic Injury

    Science.gov (United States)

    Hullinger, Thomas G.; Montgomery, Rusty L.; Seto, Anita G.; Dickinson, Brent A.; Semus, Hillary M.; Lynch, Joshua M.; Dalby, Christina M.; Robinson, Kathryn; Stack, Christianna; Latimer, Paul A.; Hare, Joshua M.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Rationale Myocardial infarction (MI) is a leading cause of death worldwide. Because endogenous cardiac repair mechanisms are not sufficient for meaningful tissue regeneration, MI results in loss of cardiac tissue and detrimental remodeling events. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression in a sequence dependent manner. Our previous data indicate that miRNAs are dysregulated in response to ischemic injury of the heart and actively contribute to cardiac remodeling after MI. Objective This study was designed to determine whether miRNAs are dysregulated on ischemic damage in porcine cardiac tissues and whether locked nucleic acid (LNA)-modified anti-miR chemistries can target cardiac expressed miRNAs to therapeutically inhibit miR-15 on ischemic injury. Methods and Results Our data indicate that the miR-15 family, which includes 6 closely related miRNAs, is regulated in the infarcted region of the heart in response to ischemia-reperfusion injury in mice and pigs. LNA-modified chemistries can effectively silence miR-15 family members in vitro and render cardiomyocytes resistant to hypoxia-induced cardiomyocyte cell death. Correspondingly, systemic delivery of miR-15 anti-miRs dose-dependently represses miR-15 in cardiac tissue of both mice and pigs, whereas therapeutic targeting of miR-15 in mice reduces infarct size and cardiac remodeling and enhances cardiac function in response to MI. Conclusions Oligonucleotide-based therapies using LNA-modified chemistries for modulating cardiac miRNAs in the setting of heart disease are efficacious and validate miR-15 as a potential therapeutic target for the manipulation of cardiac remodeling and function in the setting of ischemic injury. PMID:22052914

  8. Cardiac rhabdomyosarcoma

    OpenAIRE

    Chlumský, Jaromír; Holá, Dana; Hlaváček, Karel; Michal, Michal; Švec, Alexander; Špatenka, Jaroslav; Dušek, Jan

    2001-01-01

    Cardiac sarcoma is a very rare neoplasm and is difficult to diagnose. The case of a 51-year-old man with a left atrial tumour, locally recurrent three months after its surgical removal, is presented. Computed tomography showed metastatic spread to the lung parenchyma. On revised histology, the mass extirpated was a sarcoma. Because of the metastatic spread, further therapy was symptomatic only; the patient died 15 months after the first manifestation of his problems. Immunohistochemical stain...

  9. Cardiac Calcification

    Directory of Open Access Journals (Sweden)

    Morteza Joorabian

    2011-05-01

    Full Text Available There is a spectrum of different types of cardiac"ncalcifications with the importance and significance"nof each type of cardiac calcification, especially"ncoronary artery calcification. Radiologic detection of"ncalcifications within the heart is quite common. The"namount of coronary artery calcification correlates"nwith the severity of coronary artery disease (CAD."nCalcification of the aortic or mitral valve may indicate"nhemodynamically significant valvular stenosis."nMyocardial calcification is a sign of prior infarction,"nwhile pericardial calcification is strongly associated"nwith constrictive pericarditis. A spectrum of different"ntypes of cardiac calcifications (linear, annular,"ncurvilinear,... could be seen in chest radiography and"nother imaging modalities. So a carful inspection for"ndetection and reorganization of these calcifications"nshould be necessary. Numerous modalities exist for"nidentifying coronary calcification, including plain"nradiography, fluoroscopy, intravascular ultrasound,"nMRI, echocardiography, and conventional, helical and"nelectron-beam CT (EBCT. Coronary calcifications"ndetected on EBCT or helical CT can be quantifie,"nand a total calcification score (Cardiac Calcification"nScoring may be calculated. In an asymptomatic"npopulation and/or patients with concomitant risk"nfactors like diabetes mellitus, determination of the"npresence of coronary calcifications identifies the"npatients at risk for future myocardial infarction and"ncoronary artery disease. In patients without coronary"ncalcifications, future cardiovascular events could"nbe excluded. Therefore, detecting and recognizing"ncalcification related to the heart on chest radiography"nand other imaging modalities such as fluoroscopy, CT"nand echocardiography may have important clinical"nimplications.

  10. Trends in Cardiac Pacemaker Batteries

    Directory of Open Access Journals (Sweden)

    Venkateswara Sarma Mallela

    2004-10-01

    Full Text Available Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future.

  11. Chronic vagal stimulation for the treatment of low ejection fraction heart failure : results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    NARCIS (Netherlands)

    Zannad, Faiez; De Ferrari, Gaetano M; Tuinenburg, Anton E; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis; Castel, Maria Angeles; D'Onofrio, Antonio; Solomon, Scott D; Wold, Nicholas; Ruble, Stephen B

    2015-01-01

    AIM: The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure p

  12. Development of cardiac conduction system in mammals with a focus on the anatomical, functional and medical/genetical aspects

    Czech Academy of Sciences Publication Activity Database

    Sedmera, David

    2007-01-01

    Roč. 5, - (2007), s. 115-123. ISSN 1214-021X Institutional research plan: CEZ:AV0Z50450515 Keywords : myocyte * AV junction * Wolf- Parkinson -White syndrome * ventricular CCS * cardiac disease Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  13. The relationship between gap junctional remodeling and human atrial fibrillation

    Institute of Scientific and Technical Information of China (English)

    李大强; 冯义柏; 张会琴

    2004-01-01

    @@ Atrial fibrillation (AF) is currently the most common cardiac tachyarrhythmia in clinical practice. AF has a tendency to become more persistent over time. Progression of an underlying disease is one explanation. Another possible explanation is electrical, structural, and gap junctional remodeling of the atrium by repetitive induction of AF.1 The expression level and distribution of it have close relation with the conduction velocity of electrical activation in the atrium. The aim of the present study was to investigate the alternations of the expression and distribution of (connexin 40, Cx 40) and (connexin 43, Cx 43) in the right atrial appendages of the patients with AF by laser confocal scanning microscopy and Western blot technique.

  14. Selective homocysteine lowering gene transfer improves infarct healing, attenuates remodelling, and enhances diastolic function after myocardial infarction in mice.

    Directory of Open Access Journals (Sweden)

    Ilayaraja Muthuramu

    Full Text Available BACKGROUND AND AIMS: Homocysteine levels predict heart failure incidence in prospective epidemiological studies and correlate with severity of heart failure in cross-sectional surveys. The objective of this study was to evaluate whether a selective homocysteine lowering intervention beneficially affects cardiac remodelling and cardiac function after myocardial infarction (MI in a murine model of combined hypercholesterolemia and hyperhomocysteinemia. METHODOLOGY AND PRINCIPAL FINDINGS: A selective homocysteine lowering gene transfer strategy was evaluated in female C57BL/6 low density lipoprotein receptor (Ldlr⁻/⁻ cystathionine-ß-synthase (Cbs⁺/⁻ deficient mice fed a hyperhomocysteinemic and high saturated fat/high cholesterol diet using an E1E3E4-deleted hepatocyte-specific adenoviral vector expressing Cbs (AdCBS. MI was induced by permanent ligation of the left anterior descending coronary artery 14 days after saline injection or gene transfer. AdCBS gene transfer resulted in a persistent more than 5-fold (p<0.01 decrease of plasma homocysteine levels and significantly improved endothelial progenitor cell function. Selective homocysteine lowering enhanced infarct healing as indicated by a 21% (p<0.01 reduction of infarct length at day 28 after MI and by an increased number of capillaries and increased collagen content in the infarct zone. Adverse remodelling was attenuated in AdCBS MI mice as evidenced by a 29% (p<0.05 reduction of left ventricular cavity area at day 28, by an increased capillary density in the remote myocardium, and by reduced interstitial collagen. The peak rate of isovolumetric relaxation was increased by 19% (p<0.05 and the time constant of left ventricular relaxation was reduced by 21% (p<0.05 in AdCBS MI mice compared to control MI mice, indicating improved diastolic function. CONCLUSION/SIGNIFICANCE: Selective homocysteine lowering gene transfer improves infarct healing, attenuates remodelling, and

  15. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

    Science.gov (United States)

    Sala, Valentina; Gatti, Stefano; Gallo, Simona; Medico, Enzo; Cantarella, Daniela; Cimino, James; Ponzetto, Antonio; Crepaldi, Tiziana

    2016-01-01

    Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level. PMID:27298830

  16. A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

    Directory of Open Access Journals (Sweden)

    Valentina Sala

    2016-01-01

    Full Text Available Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level.

  17. Impact on Left Ventricular Function and Remodeling and on 1-Year Outcome in Patients With Left Bundle Branch Block After Transcatheter Aortic Valve Implantation.

    Science.gov (United States)

    Carrabba, Nazario; Valenti, Renato; Migliorini, Angela; Marrani, Marco; Cantini, Giulia; Parodi, Guido; Dovellini, Emilio Vincenzo; Antoniucci, David

    2015-07-01

    Conflicting results have been reported about the prognostic impact of left bundle branch block (LBBB) after transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the impact of LBBB after TAVI on left ventricular (LV) function and remodeling and on 1-year outcomes. Of 101 TAVI patients, 9 were excluded. All complications were evaluated according to the Valve Academic Research Consortium 2 definition. Of 92 patients, 34 developed LBBB without more advanced myocardial damage or inflammation biomarkers in comparison with patients without LBBB. The only predictor of new LBBB was larger baseline LV end-diastolic volume. LBBB plus advanced atrioventricular block was strongly correlated with permanent pacemaker implantation (p reverse remodeling at 1 year. The development of acute kidney injury and the logistic European System for Cardiac Operative Risk Evaluation score were associated with poor outcomes (all-cause mortality and heart failure) (hazard ratio 6.86, 95% confidence interval 2.51 to 18.74, p <0.0001, and hazard ratio 1.04, 95% confidence interval 1.01 to 1.08, p = 0.021, respectively), but not LBBB. In conclusion, after TAVI, 37% of patients developed new LBBB without more advanced myocardial damage or inflammation biomarkers. LBBB was associated with a higher rate of permanent pacemaker implantation, which negatively affected the recovery of LV systolic function. The development of acute kidney injury, rather than LBBB, increases the 1-year risk for mortality and hospitalization for heart failure. PMID:25937352

  18. Tricuspid annular plane systolic excursion and response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Ghio, Stefano; St John Sutton, Martin;

    2011-01-01

    The aims of this study were to evaluate tricuspid annular plane systolic excursion (TAPSE) as a predictor of left ventricular (LV) reverse remodeling and clinical benefit of cardiac synchronization therapy (CRT) and to evaluate the effect of CRT on TAPSE in patients with mildly symptomatic systolic...... heart failure as a substudy of the REsyncronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) trial....

  19. Renovascular hypertension causes cerebral vascular remodeling

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Xiangpen Li; Yi Li; Qingyu Shen; Xiaoming Rong; Ruxun Huang; Ying Peng

    2011-01-01

    Renovascular hypertensive rats (RHRs) were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

  20. Remodeling dan Repairing Vaskular pada Nefropati Hipertensif

    OpenAIRE

    Rasyid, Haerani; Wijaya, Johnson; Bakri, Syakib

    2011-01-01

    Latar Belakang: Ketidakseimbangan proses remodeling dan repairing vaskular diduga berperan penting pada kekakuan dan ketebalan vaskular yang akhirnya menyebabkan komplikasi hipertensi. Petanda dini komplikasi hipertensi pada ginjal adalah adanya mikroalbuminuria (MA). Tujuan Penelitian: Untuk mengetahui perbedaan konsentrasi TGF-??1 (sebagai petanda remodeling) dan VEGFR-2 (sebagai petanda repairing) pada subyek normotensi, hipertensi normoalbuminuria (NA) dan hipertensi MA. Metode: P...

  1. Multiscale Simulation of Protein Mediated Membrane Remodeling

    OpenAIRE

    Ayton, Gary S.; Voth, Gregory A.

    2009-01-01

    Proteins interacting with membranes can result in substantial membrane deformations and curvatures. This effect is known in its broadest terms as membrane remodeling. This review article will survey current multiscale simulation methodologies that have been employed to examine protein-mediated membrane remodeling.

  2. Dietary ω-3 Fatty Acids Alter Cardiac Mitochondrial Phospholipid Composition and Delay Ca2+-Induced Permeability Transition

    OpenAIRE

    O’Shea, Karen M.; Khairallah, Ramzi J.; Sparagna, Genevieve C.; Xu, Wenhong; Hecker, Peter A; Robillard-Frayne, Isabelle; Des Rosiers, Christine; Kristian, Tibor; Robert C. Murphy; Fiskum, Gary; Stanley, William C.

    2009-01-01

    Consumption of ω-3 fatty acids from fish oil, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), decreases risk for heart failure and attenuates pathologic cardiac remodeling in response to pressure overload. Dietary supplementation with EPA+DHA may also impact cardiac mitochondrial function and energetics through alteration of membrane phospholipids. We assessed the role of EPA+DHA supplementation on left ventricular (LV) function, cardiac mitochondrial membrane phospho...

  3. C-Reactive Protein Inhibits Survivin Expression via Akt/mTOR Pathway Downregulation by PTEN Expression in Cardiac Myocytes

    OpenAIRE

    Beom Seob Lee; Soo Hyuk Kim; Jaewon Oh; Taewon Jin; Eun Young Choi; Sungha Park; Sang-Hak Lee; Ji Hyung Chung; Seok-Min Kang

    2014-01-01

    C-reactive protein (CRP) is one of the most important biomarkers for arteriosclerosis and cardiovascular disease. Recent studies have shown that CRP affects cell cycle and inflammatory process in cardiac myocytes. Survivin is also involved in cardiac myocytes replication and apoptosis. Reduction of survivin expression is associated with less favorable cardiac remodeling in animal models. However, the effect of CRP on survivin expression and its cellular mechanism has not yet been studied. We ...

  4. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    Science.gov (United States)

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. PMID:27056419

  5. Hepato-cardiac disorders

    Institute of Scientific and Technical Information of China (English)

    Yasser; Mahrous; Fouad; Reem; Yehia

    2014-01-01

    Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases

  6. Primary cardiac tumors

    International Nuclear Information System (INIS)

    Cardiac tumors happen to be among the less known pathologies without clear treatment standards. Even one decade ago most of the cardiac tumor diagnosis were made post mortem, and only reports of isolated cases could be found in the literature, showing the lack of interest in the investigation of these pathologies by cardiology and cardiovascular surgery specialists. With the development of echocardiography and of cardiovascular surgery, more cases of primary and metastatic cardiac tumors have been diagnosed. Many cases have been treated by palliative or curative surgical interventions, thus increasing the reports in the world literature and the experience in this field, and pointing out the real incidence of these pathologies, not being as bizarre as it had been considered. a revision of the literature will be made, in which the frequency and the suggested interventions will be reported, as well as the cases of cardiac pathology in two cardiovascular centers of the country known by the author. The echocardiographic, pathologic and histological characteristics of the representative cases will be presented, without a greater evidence level, due to the problem's incidence and the few cases reported by these centers

  7. Nucleosome dynamics during chromatin remodeling in vivo.

    Science.gov (United States)

    Ramachandran, Srinivas; Henikoff, Steven

    2016-01-01

    Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790

  8. Evaluation of left ventricular remodelling in patients with chronic ischemic heart disease using multislice computer tomography and magnetic resonance tomography

    International Nuclear Information System (INIS)

    The article presents the results of MSCT and MRI of the heart in 57 patients with chronic coronary heart disease. It determined the relationship between structural and functional changes in the left ventricle and the degree of left coronary artery stenosis. Also determined were the link between the ischemic left ventricular remodeling and depth of myocardial damage in patients with coronary heart disease and postinfarction cardiosclerosis. MSCT and MRI are highly reliable imaging technique used to evaluate the infarcted and viable myocardium and post infarct cardiac remodeling process

  9. A heart-hand syndrome gene: Tfap2b plays a critical role in the development and remodeling of mouse ductus arteriosus and limb patterning.

    Directory of Open Access Journals (Sweden)

    Feng Zhao

    Full Text Available BACKGROUND: Patent ductus arteriosus (PDA is one of the most common forms of congenital heart disease. Mutations in transcription factor TFAP2B cause Char syndrome, a human disorder characterized by PDA, facial dysmorphysm and hand anomalies. Animal research data are needed to understand the mechanisms. The aim of our study was to elucidate the pathogenesis of Char syndrome at the molecular level. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression of Tfap2b during mouse development was studied, and newborns of Tfap2b-deficient mice were examined to identify phenotypes. Gel shift assays had been carried out to search for Tfap2 downstream genes. Promoters of candidate genes were cloned into a reporter construct and used to demonstrate their regulation by Tfap2b in cell transfection. In situ hybridizations showed that the murine transcription factor Tfap2b was expressed during the entire development of mouse ductus arteriosus. Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. Consequently, the lungs of Tfap2b(-/- mice demonstrated progressive congestion of the pulmonary capillaries, which was postulated to result secondarily from PDA. In addition, Tfap2b was expressed in the limb buds, particularly in the posterior limb field during development. Lack of Tfap2b resulted in bilateral postaxial accessory digits. Further study indicated that expressions of bone morphogenetic protein (Bmp genes, which are reported to be involved in the limb patterning and ductal development, were altered in limb buds of Tfap2b-deficient embryos, due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b. CONCLUSIONS/SIGNIFICANCE: Tfap2b plays important roles in the development of mouse ductus arteriosus and limb patterning. Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in Tfap2b mouse mutants and Char syndrome patients. The Tfap2b knockout

  10. Cardiac conduction system

    Science.gov (United States)

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  11. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    Directory of Open Access Journals (Sweden)

    Mugoša S

    2016-08-01

    Full Text Available Snežana Mugoša,1,2 Nataša Djordjević,3 Nina Djukanović,4 Dragana Protić,5 Zoran Bukumirić,6 Ivan Radosavljević,7 Aneta Bošković,8 Zoran Todorović5,9 1Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro, 2Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro; 3Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, 4High Medical School “Milutin Milanković”, Belgrade, 5Department of Pharmacology, Clinical Pharmacology and Toxicology, 6Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, 7Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia; 8Clinic for Heart Diseases, Clinical Centre of Montenegro, Podgorica, Montenegro; 9Department of Clinical Immunology and Allergy, Medical Center “Bežanijska kosa”, Belgrade, Serbia Abstract: The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6 poor metabolizer alleles (*3, *4, *5, and *6 on a Montenegrin population and its impact on developing adverse drug reactions (ADRs of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9% patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001, with ADRs’ occurrence significantly

  12. Thyroid Hormone and Vascular Remodeling.

    Science.gov (United States)

    Ichiki, Toshihiro

    2016-03-01

    Both hyperthyroidism and hypothyroidism affect the cardiovascular system. Hypothyroidism is known to be associated with enhanced atherosclerosis and ischemic heart diseases. The accelerated atherosclerosis in the hypothyroid state has been traditionally ascribed to atherogenic lipid profile, diastolic hypertension, and impaired endothelial function. However, recent studies indicate that thyroid hormone has direct anti-atherosclerotic effects, such as production of nitric oxide and suppression of smooth muscle cell proliferation. These data suggest that thyroid hormone inhibits atherogenesis through direct effects on the vasculature as well as modification of risk factors for atherosclerosis. This review summarizes the basic and clinical studies on the role of thyroid hormone in vascular remodeling. The possible application of thyroid hormone mimetics to the therapy of hypercholesterolemia and atherosclerosis is also discussed. PMID:26558400

  13. Obesity and carotid artery remodeling

    DEFF Research Database (Denmark)

    Kozakova, M; Palombo, C; Morizzo, C;

    2015-01-01

    BACKGROUND/OBJECTIVE: The present study tested the hypothesis that obesity-related changes in carotid intima-media thickness (IMT) might represent not only preclinical atherosclerosis but an adaptive remodeling meant to preserve circumferential wall stress (CWS) in altered hemodynamic conditions...... and CCA LD (266 healthy subjects with wide range of body weight (24-159 kg)); (B) longitudinal associations between CCA LD and 3-year IMT progression rate (ΔIMT; 571 healthy non-obese subjects without increased cardiovascular (CV) risk); (C) the impact of obesity on CCA geometry and CWS (88 obese...... subjects without CV complications and 88 non-obese subjects matched for gender and age). RESULTS: CCA LD was independently associated with SV that was determined by body size. In the longitudinal study, baseline LD was an independent determinant of ΔIMT, and ΔIMT of subjects in the highest LD quartile was...

  14. Optical coherence tomography. A new high-resolution imaging technology to study cardiac development in chick embryos

    DEFF Research Database (Denmark)

    Yelbuz, T.M.; Choma, M.A.; Thrane, L.;

    2002-01-01

    Background-Optical coherence tomography (OCT) is a depth-resolved, noninvasive, non-destructive imaging modality, the use of which has yet to be fully realized in developmental biology. Methods and Results-We visualized embryonic chick hearts at looping stages using an OCT system with a 22 mum...... axial and 27 mum lateral resolution and an acquisition rate of 4000 A-scans per second. Normal chick embryos from stages 14 to 22 and sham-operated and cardiac neural crest-ablated embryos from stages 15 and 18 were scanned by OCT. Three-dimensional data sets were acquired and processed to create...... volumetric reconstructions and short video clips. The OCT-scanned embryos (2 in each group) were photographed after histological sectioning in comparable planes to those visualized by OCT. The optical and histological results showing cardiovascular microstructures such as myocardium, the cardiac jelly, and...

  15. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  16. Cardiovascular function, compliance, and connective tissue remodeling in the turtle, Trachemys scripta, following thermal acclimation.

    Science.gov (United States)

    Keen, Adam N; Shiels, Holly A; Crossley, Dane A

    2016-07-01

    Low temperature directly alters cardiovascular physiology in freshwater turtles, causing bradycardia, arterial hypotension, and a reduction in systemic blood pressure. At the same time, blood viscosity and systemic resistance increase, as does sensitivity to cardiac preload (e.g., via the Frank-Starling response). However, the long-term effects of these seasonal responses on the cardiovascular system are unclear. We acclimated red-eared slider turtles to a control temperature (25°C) or to chronic cold (5°C). To differentiate the direct effects of temperature from a cold-induced remodeling response, all measurements were conducted at the control temperature (25°C). In anesthetized turtles, cold acclimation reduced systemic resistance by 1.8-fold and increased systemic blood flow by 1.4-fold, resulting in a 2.3-fold higher right to left (R-L; net systemic) cardiac shunt flow and a 1.8-fold greater shunt fraction. Following a volume load by bolus injection of saline (calculated to increase stroke volume by 5-fold, ∼2.2% of total blood volume), systemic resistance was reduced while pulmonary blood flow and systemic pressure increased. An increased systemic blood flow meant the R-L cardiac shunt was further pronounced. In the isolated ventricle, passive stiffness was increased following cold acclimation with 4.2-fold greater collagen deposition in the myocardium. Histological sections of the major outflow arteries revealed a 1.4-fold higher elastin content in cold-acclimated animals. These results suggest that cold acclimation alters cardiac shunting patterns with an increased R-L shunt flow, achieved through reducing systemic resistance and increasing systemic blood flow. Furthermore, our data suggests that cold-induced cardiac remodeling may reduce the stress of high cardiac preload by increasing compliance of the vasculature and decreasing compliance of the ventricle. Together, these responses could compensate for reduced systolic function at low temperatures in

  17. Beyond the Genome: Epigenetic Mechanisms in Lung Remodeling

    OpenAIRE

    Hagood, James S

    2014-01-01

    The lung develops from a very simple outpouching of the foregut into a highly complex, finely structured organ with multiple specialized cell types that are required for its normal physiological function. During both the development of the lung and its remodeling in the context of disease or response to injury, gene expression must be activated and silenced in a coordinated manner to achieve the tremendous phenotypic heterogeneity of cell types required for homeostasis and pathogenesis. Epige...

  18. Cardiac surgery outcomes.

    Science.gov (United States)

    Halpin, Linda S; Barnett, Scott D; Beachy, Jim

    2003-01-01

    Accrediting organizations and payers are demanding valid and reliable data that demonstrate the value of services. Federal agencies, healthcare industry groups, and healthcare watchdog groups are increasing the demand for public access to outcomes data. A new and growing outcomes dynamic is the information requested by prospective patients in an increasingly consumer-oriented business. Patients demand outcomes, and resources are developing to meet these demands. Physicians are increasingly confronted with requests for information about their mortality and morbidity rates, malpractice suits, and disciplinary actions received. For example, in Virginia, prospective patients have access to data provided by the nonprofit group Virginia Health Information. After numerous resolutions by the Virginia Senate since 1999, the prospective Virginia medical consumer now has access to several annual publications: Virginia Hospitals: A Consumer's Guide, 1999 Annual Report and Strategic Plan Update, and the 1999 Industry Report: Virginia Hospitals and Nursing Facilities. Consumers have access to cardiac outcomes data stratified by hospital, gender, and cardiac service line (cardiac surgery, noninvasive cardiology, and invasive cardiology). This is particularly relevant to IHI because Virginia Health Information specifically targets cardiac care. IHI has a sizable investment in cardiovascular outcomes and has found outcomes measurement and research are key to providing quality care. IHI's goal is to move from an outcomes management model to a disease management model. The hope is to incorporate all aspects of the patient's continuum of care, from preoperative and diagnostic services through cardiac interventions to postoperative rehabilitation. Furthermore, every step along the way will be supported with functional status and quality of life assessments. Although these goals are ambitious and expensive, the return on investment is high. PMID:14618772

  19. Multislice Cardiac CT-Angiography; A Review on Accepted Indications and Potentials for Other Applications Regarding the Newest Development

    Directory of Open Access Journals (Sweden)

    M. Motevalli

    2007-05-01

    Full Text Available There were not any clear-cut criteria available for clinical use of cardiac CT-angiography (CCTA up to October 2006 in which the American College of Car-diology (ACC, American College of Radiology (ACR and six other medical institutions released a joint consensus on clinical indications of cardiac CT and MRI. A statement was released by the American Heart Association together with two other radiology and cardiology institutions in the same month on the same matter. An illustrated review will be presented on the newly accepted indications of cardiac CT, especially CCTA. Some prominent indications are as follow: 1. Evaluation of chest pain syndrome in patient with intermediate pretest probability of coronary artery disease (CAD when exercise test is not feasible. 2. Evaluation of acute chest pain in patient with in-termediate pretest probability of CAD and negative ECG and enzymes. 3. Uninterpretable or equivocal stress test (exercise, perfusion scan, or stress echo. 4. Evaluation of coronary arteries in patients with new onset heart failure. 5. Assessment of congenital coronary and cardiac anomalies. 6. Noninvasive coronary vein mapping prior to placement of biventricular pacemaker. 7. Noninvasive coronary arterial mapping, including internal mammary artery prior to repeat cardiac sur-gical revascularization. Some recent research indicated that CCTA is useful in some other specific situations too, like evaluating in-stent re-stenosis for stainless steel or cobalt stents more than 3mm in diameter and has also some roles in the evaluation of coronary bypass grafts, etc. Fi-nally, the newer progressions in the field of multislice CT are promising of even better performance which may widen the scope of its indications. Dual-source CT scanners have shown better performance com-pared with 64-slice CT scanners in the preliminary studies, namely slice-thickness of 0.25mm vs. 0.4mm, temporal resolution of 83ms vs.165ms, assessable segments of 98.6% vs. 97

  20. Protective role of heme oxygenase-1 in atrial remodeling.

    Science.gov (United States)

    Yeh, Yung-Hsin; Hsu, Lung-An; Chen, Ying-Hwa; Kuo, Chi-Tai; Chang, Gwo-Jyh; Chen, Wei-Jan

    2016-09-01

    Structural and electrical remodeling in the atrium constitutes the main feature of atrial fibrillation (AF), which is characterized by increased oxidative stress. Heme oxygenase-1 (HO-1) is a potent anti-oxidant system that may provide protection against various oxidative stress-related diseases. The aim of this study is to investigate whether HO-1 has a protective effect on AF-related remodeling. Cultured atrium-derived myocytes (HL-1 cell line) were used to evaluate tachypacing-induced oxidative stress, structural, and electrical remodeling. Transforming growth factor-β (TGF-β) was utilized to assess collagen (a main fibrosis-related protein) expression in atrial fibroblasts. Tachypacing in HL-1 myocytes and treatment of atrial fibroblasts with TGF-β enhanced the expression of HO-1, both of which were mediated by the activation of nuclear factor erythroid-2-related factor 2. Over-expression of HO-1 in HL-1 cells attenuated tachypacing-induced oxidative stress, myofibril degradation, down-regulation of L-type calcium channel, and shortening of action potential duration. Furthermore, HO-1 over-expression in atrial fibroblasts blocked the up-regulation of collagen by TGF-β, implicating a protective role of HO-1 in structural and electrical remodeling in the atrium. In vivo, HO-1(-/-) mice exhibited a higher degree of oxidative stress, myofibril degradation, and collagen deposit in their atria than wild-type mice. Moreover, burst atrial pacing induced a greater susceptibility to AF in HO-1(-/-) mice than in wild-type mice. In conclusion, a negative-feedback regulation of HO-1 in activated atrial myocytes and fibroblasts may provide protection against AF-related remodeling and AF development. PMID:27562817

  1. Metoclopramide-induced cardiac arrest

    Directory of Open Access Journals (Sweden)

    Martha M. Rumore

    2011-11-01

    Full Text Available The authors report a case of cardiac arrest in a patient receiving intravenous (IV metoclopramide and review the pertinent literature. A 62-year-old morbidly obese female admitted for a gastric sleeve procedure, developed cardiac arrest within one minute of receiving metoclopramide 10 mg via slow intravenous (IV injection. Bradycardia at 4 beats/min immediately appeared, progressing rapidly to asystole. Chest compressions restored vital function. Electrocardiogram (ECG revealed ST depression indicative of myocardial injury. Following intubation, the patient was transferred to the intensive care unit. Various cardiac dysrrhythmias including supraventricular tachycardia (SVT associated with hypertension and atrial fibrillation occurred. Following IV esmolol and metoprolol, the patient reverted to normal sinus rhythm. Repeat ECGs revealed ST depression resolution without pre-admission changes. Metoclopramide is a non-specific dopamine receptor antagonist. Seven cases of cardiac arrest and one of sinus arrest with metoclopramide were found in the literature. The metoclopramide prescribing information does not list precautions or adverse drug reactions (ADRs related to cardiac arrest. The reaction is not dose related but may relate to the IV administration route. Coronary artery disease was the sole risk factor identified. According to Naranjo, the association was possible. Other reports of cardiac arrest, severe bradycardia, and SVT were reviewed. In one case, five separate IV doses of 10 mg metoclopramide were immediately followed by asystole repeatedly. The mechanism(s underlying metoclopramide’s cardiac arrest-inducing effects is unknown. Structural similarities to procainamide may play a role. In view of eight previous cases of cardiac arrest from metoclopramide having been reported, further elucidation of this ADR and patient monitoring is needed. Our report should alert clinicians to monitor patients and remain diligent in surveillance and

  2. [EFFICACY OF STANDARD TWO-YEAR COMPREHENSIVE THERAPY TO ACHIEVE TARGET BLOOD PRESSURE AND REGRESSION DEGREES OF REMODELING OF THE LEFT VENTRICULAR HYPERTROPHY IN PATIENTS AFTER ACUTE MYOCARDIAL INFARCTION WITH COMORBID HYPERTENSION].

    Science.gov (United States)

    Denesiuk, E V

    2015-01-01

    The study involved 23 men after acute myocardial infarction (AMI) with comorbid arterial hypertension (AH). Mean age of patients was 56.7 years. Recurrent myocardial infarction was determined in 38.4%, cardiac failure I-III functional classes--100% of the cases. All patients underwent clinical examination, electrocardiography and echocardiography, blood lipid profile. Standard comprehensive treatment for two years included an perindopril 5-10 mg/day, beta-blocker bisoprolol--5-10 mg/day, antisclerotic drug atorvastatin--20 mg/day and aspirin--75 mg/day. The patients after treatment was determined by a gradual increase towards the target of AT at 3, 6 and 12 to 24 months. Concentric left ventricular hypertrophy (LVH) before treatment was determined in 47.8%, eccentric--in 52.2% of patients. In the study of degrees of LVH I (initial) the extent to treatment was determined by 4.3%, II (moderate)--26.1%, III (large)--at 69.6%, indicating the development of cardiac remodeling. After the treatment was determined by marked reduction III (large) degree and transfer it in the II (moderate) and I (small) degree of left ventricular hypertrophy due to more or less pronounced changes remodeling left ventricular. The obtained data allow a more detailed and adequately assess the structural and functional outcome variables and determine the regression of myocardial hypertrophy in the background to achieve target blood pressure, which is important in practical cardiology. PMID:27491146

  3. Cardiac developmental toxicity

    OpenAIRE

    Mahler, Gretchen J.; Jonathan T Butcher

    2011-01-01

    Congenital heart disease is a highly prevalent problem with mostly unknown origins. Many cases of CHD likely involve an environmental exposure coupled with genetic susceptibility, but practical and ethical considerations make nongenetic causes of CHD difficult to assess in humans. The development of the heart is highly conserved across all vertebrate species, making animal models an excellent option for screening potential cardiac teratogens. This review will discuss exposures known to cause ...

  4. Role of atrial tissue remodeling on rotor dynamics: an in vitro study.

    Science.gov (United States)

    Climent, Andreu M; Guillem, María S; Fuentes, Lucia; Lee, Peter; Bollensdorff, Christian; Fernández-Santos, María Eugenia; Suárez-Sancho, Susana; Sanz-Ruiz, Ricardo; Sánchez, Pedro Luis; Atienza, Felipe; Fernández-Avilés, Francisco

    2015-12-01

    The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF. PMID:26408535

  5. The cardiac enigma: current conundrums in heart failure research [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Michael S. Kapiloff

    2016-01-01

    Full Text Available The prevalence of heart failure is expected to increase almost 50% in the next 15 years because of aging of the general population, an increased frequency of comorbidities, and an improved survival following cardiac events. Conventional treatments for heart failure have remained largely static over the past 20 years, illustrating the pressing need for the discovery of novel therapeutic agents for this patient population. Given the heterogeneous nature of heart failure, it is important to specifically define the cellular mechanisms in the heart that drive the patient’s symptoms, particularly when considering new treatment strategies. This report highlights the latest research efforts, as well as the possible pitfalls, in cardiac disease translational research and discusses future questions and considerations needed to advance the development of new heart failure therapies. In particular, we discuss cardiac remodeling and the translation of animal work to humans and how advancements in our understanding of these concepts relative to disease are central to new discoveries that can improve cardiovascular health.

  6. Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice

    OpenAIRE

    Merentie, Mari; Jukka A Lipponen; Hedman, Marja; Hedman, Antti; Hartikainen, Juha; Huusko, Jenni; Lottonen‐Raikaslehto, Line; Parviainen, Viktor; Laidinen, Svetlana; KARJALAINEN, Pasi A.; Ylä‐Herttuala, Seppo

    2015-01-01

    Abstract Mouse models are extremely important in studying cardiac pathologies and related electrophysiology, but very few mouse ECG analysis programs are readily available. Therefore, a mouse ECG analysis algorithm was developed and validated. Surface ECG (lead II) was acquired during transthoracic echocardiography from C57Bl/6J mice under isoflurane anesthesia. The effect of aging was studied in young (2–3 months), middle‐aged (14 months) and old (20–24 months) mice. The ECG changes associat...

  7. Cholinergic Regulation of Airway Inflammation and Remodelling

    Directory of Open Access Journals (Sweden)

    Saeed Kolahian

    2012-01-01

    Full Text Available Acetylcholine is the predominant parasympathetic neurotransmitter in the airways that regulates bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine regulates additional functions in the airways, including inflammation and remodelling during inflammatory airway diseases. Moreover, it has become apparent that acetylcholine is synthesized by nonneuronal cells and tissues, including inflammatory cells and structural cells. In this paper, we will discuss the regulatory role of acetylcholine in inflammation and remodelling in which we will focus on the role of the airway smooth muscle cell as a target cell for acetylcholine that modulates inflammation and remodelling during respiratory diseases such as asthma and COPD.

  8. Genome-wide analysis of interactions between ATP-dependent chromatin remodeling and histone modifications

    Directory of Open Access Journals (Sweden)

    Wang Jiang

    2009-07-01

    Full Text Available Abstract Background ATP-dependent chromatin remodeling and the covalent modification of histones play central roles in determining chromatin structure and function. Although several specific interactions between these two activities have been elaborated, the global landscape remains to be elucidated. Results In this paper, we have developed a computational method to generate the first genome-wide landscape of interactions between ATP-dependent chromatin remodeling and the covalent modification of histones in Saccharomyces cerevisiae. Our method succeeds in identifying known interactions and uncovers many previously unknown interactions between these two activities. Analysis of the genome-wide picture revealed that transcription-related modifications tend to interact with more chromatin remodelers. Our results also demonstrate that most chromatin remodeling-modification interactions act via interactions of remodelers with both histone-modifying enzymes and histone residues. We also found that the co-occurrence of both modification and remodeling has significantly different influences on multiple gene features (e.g. nucleosome occupancy compared with the presence of either one. Conclusion We gave the first genome-wide picture of ATP-dependent chromatin remodeling-histone modification interactions. We also revealed how these two activities work together to regulate chromatin structure and function. Our results suggest that distinct strategies for regulating chromatin activity are selectively employed by genes with different properties.

  9. Robotic Applications in Cardiac Surgery

    Directory of Open Access Journals (Sweden)

    Alan P. Kypson

    2008-11-01

    Full Text Available Traditionally, cardiac surgery has been performed through a median sternotomy, which allows the surgeon generous access to the heart and surrounding great vessels. As a paradigm shift in the size and location of incisions occurs in cardiac surgery, new methods have been developed to allow the surgeon the same amount of dexterity and accessibility to the heart in confined spaces and in a less invasive manner. Initially, long instruments without pivot points were used, however, more recent robotic telemanipulation systems have been applied that allow for improved dexterity, enabling the surgeon to perform cardiac surgery from a distance not previously possible. In this rapidly evolving field, we review the recent history and clinical results of using robotics in cardiac surgery.

  10. Temporal patterns of electrical remodeling in canine ventricular hypertrophy: Focus on I-Ks downregulation and blunted beta-adrenergic activation

    NARCIS (Netherlands)

    M. Stengl; C. Ramakers; D.W. Donker; A. Nabar; A.V. Rybin; R.L.H.M.G. Spatjens; T. van der Nagel; W.K.W.H. Wodzig; K.R. Sipido; G. Antoons; A.F.M. Moorman; M.A. Vos; P.G.A. Volders

    2006-01-01

    Objectives: Electrical remodeling in cardiac hypertrophy often involves the downregulation of K+ currents, including beta-adrenergic (beta-A)-sensitive I-Ks. Temporal patterns of ion-channel downregulation are poorly resolved. In dogs with complete atrioventricular block (AVB), we examined (1) the t

  11. Mannose-binding lectin (MBL) insufficiency protects against the development of systemic inflammatory response after pediatric cardiac surgery.

    Science.gov (United States)

    Pągowska-Klimek, Izabela; Świerzko, Anna S; Michalski, Mateusz; Moll, Maciej; Szala-Poździej, Agnieszka; Sokołowska, Anna; Krajewski, Wojciech R; Cedzyński, Maciej

    2016-02-01

    We investigated MBL2 and MASP2 genotypes, serum MBL (mannose-binding lectin) levels and activities of its complexes with associated serine proteases (MASP-1, MASP -2), in relation to complications following cardiac surgery in 195 children. The incidence of SIRS was lower in patients carrying MBL2 A/O and O/O genotypes (p=0.024). Children with MBL levels 30) (p=0.021). Thus, low MBL concentrations and associated genotypes may protect patients from systemic inflammation while high MBL serum levels and corresponding genotypes are risk factors of postoperative complications. PMID:26382056

  12. Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance

    Science.gov (United States)

    Zhang, Xiaochun; Leng, Weiling

    2016-01-01

    Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E′, A′, and E′/A′) were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E′ (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM.

  13. Cardiac manifestations in systemic sclerosis

    Institute of Scientific and Technical Information of China (English)

    Sevdalina; Lambova

    2014-01-01

    Primary cardiac involvement, which develops as a direct consequence of systemic sclerosis(SSc), may manifest as myocardial damage, fibrosis of the conduction system, pericardial and, less frequently, as valvular disease. In addition, cardiac complications in SSc may develop as a secondary phenomenon due to pulmonary arterial hypertension and kidney pathology. The prevalence of primary cardiac involvement in SSc is variable and difficult to determine because of the diversity of cardiac manifestations, the presence of subclinical periods, the type of diagnostic tools applied, and the diversity of patient populations. When clinically manifested, cardiac involvement is thought to be an important prognostic factor. Profound microvascular disease is a pathognomonic feature of SSc, as both vasospasm and structural alterations are present. Such alterations are thought to predict macrovascular atherosclerosis over time. There are contradictory reports regarding the prevalence of atherosclerosis in SSc. According to some authors, the prevalence of atherosclerosis of the large epicardial coronary arteries is similar to that of the general population, in contrast with other rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus. However, the level of inflammation in SSc is inferior. Thus, the atherosclerotic process may not be as aggressive and not easily detectable in smaller studies. Echocardiography(especially tissue Doppler imaging), single-photon emission computed tomography, magnetic resonance imaging and cardiac computed tomography are sensitive techniques for earlier detection of both structural and functional scleroderma-related cardiac pathologies. Screening for subclinical cardiac involvement via modern, sensitive tools provides an opportunity for early diagnosis and treatment, which is of crucial importance for a positive outcome.

  14. Cardiac MRI in Athletes

    NARCIS (Netherlands)

    Luijkx, T.

    2012-01-01

    Cardiac magnetic resonance imaging (CMR) is often used in athletes to image cardiac anatomy and function and is increasingly requested in the context of screening for pathology that can cause sudden cardiac death (SCD). In this thesis, patterns of cardiac adaptation to sports are investigated with C

  15. Cardiac tissue engineering

    Directory of Open Access Journals (Sweden)

    MILICA RADISIC

    2005-03-01

    Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

  16. Vascular remodeling as compensatory changes in different degrees of varicocele

    Directory of Open Access Journals (Sweden)

    E. S. Severgina

    2013-01-01

    Full Text Available We investigated biosises obtained from children with different varicocele stages and showed the possibility of remodeling development in different type vein walls. Most typical changes were found in the third type vein walls – multiple rolls, composed of muscular and collagen bundles; in the larger first and second type veins markers of arterialization were seen. These processes are the manifestations of adaptive response, which is connected with elevated venous pressure; they can improve testicular hemodynamic.

  17. Vascular remodeling as compensatory changes in different degrees of varicocele

    Directory of Open Access Journals (Sweden)

    E. S. Severgina

    2014-11-01

    Full Text Available We investigated biosises obtained from children with different varicocele stages and showed the possibility of remodeling development in different type vein walls. Most typical changes were found in the third type vein walls – multiple rolls, composed of muscular and collagen bundles; in the larger first and second type veins markers of arterialization were seen. These processes are the manifestations of adaptive response, which is connected with elevated venous pressure; they can improve testicular hemodynamic.

  18. Quantitative computed tomography imaging of airway remodeling in severe asthma

    OpenAIRE

    Grenier, Philippe A.; Fetita, Catalin I.; Brillet, Pierre-Yves

    2016-01-01

    Asthma is a heterogeneous condition and approximately 5–10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. ...

  19. Remodeling of Calcium Handling in Human Heart Failure

    OpenAIRE

    Lou, Qing; Janardhan, Ajit; Efimov, Igor R.

    2012-01-01

    Heart failure (HF) is an increasing public health problem accelerated by a rapidly aging global population. Despite considerable progress in managing the disease, the development of new therapies for effective treatment of HF remains a challenge. To identify targets for early diagnosis and therapeutic intervention, it is essential to understand the molecular and cellular basis of calcium handling and the signaling pathways governing the functional remodeling associated with HF in humans. Calc...

  20. Maxillary Mucocele with Orbital Floor Remodelling

    OpenAIRE

    Tahrina Salam; Maryam Zamani; Jane Olver

    2012-01-01

    A 79-year-old man presents with signs of an orbital mass. A CT scan revealed a large maxillary mucocele eroding through the orbital floor. Surgical drainage of the mucocele and conservative postoperative care, returned all ophthalmic signs to normal and bony remodelling of the orbital floor was demonstrated. Maxillary mucoceles should be assessed by both ENT and Ophthalmic surgeons. Postoperative remodelling of the orbital floor can be illustrated with serial CT Scans.

  1. Ventricular structure, function, and mechanics at high altitude: chronic remodeling in Sherpa vs. short-term lowlander adaptation

    OpenAIRE

    Stembridge, Mike; Ainslie, Philip N; Hughes, Michael G.; Stöhr, Eric J.; Cotter, James D.; Nio, Amanda Q. X.; Shave, Rob

    2014-01-01

    Short-term, high-altitude (HA) exposure raises pulmonary artery systolic pressure (PASP) and decreases left-ventricular (LV) volumes. However, relatively little is known of the long-term cardiac consequences of prolonged exposure in Sherpa, a highly adapted HA population. To investigate short-term adaptation and potential long-term cardiac remodeling, we studied ventricular structure and function in Sherpa at 5,050 m (n = 11; 31 ± 13 yr; mass 68 ± 10 kg; height 169 ± 6 cm) and lowlanders at s...

  2. Methods in pharmacology: measurement of cardiac output

    OpenAIRE

    Geerts, Bart F; Aarts, Leon P; Jansen, Jos R.

    2011-01-01

    Many methods of cardiac output measurement have been developed, but the number of methods useful for human pharmacological studies is limited. The ‘holy grail’ for the measurement of cardiac output would be a method that is accurate, precise, operator independent, fast responding, non-invasive, continuous, easy to use, cheap and safe. This method does not exist today. In this review on cardiac output methods used in pharmacology, the Fick principle, indicator dilution techniques, arterial pul...

  3. Dynamics of the ethanolamine glycerophospholipid remodeling network.

    Directory of Open Access Journals (Sweden)

    Lu Zhang

    Full Text Available Acyl chain remodeling in lipids is a critical biochemical process that plays a central role in disease. However, remodeling remains poorly understood, despite massive increases in lipidomic data. In this work, we determine the dynamic network of ethanolamine glycerophospholipid (PE remodeling, using data from pulse-chase experiments and a novel bioinformatic network inference approach. The model uses a set of ordinary differential equations based on the assumptions that (1 sn1 and sn2 acyl positions are independently remodeled; (2 remodeling reaction rates are constant over time; and (3 acyl donor concentrations are constant. We use a novel fast and accurate two-step algorithm to automatically infer model parameters and their values. This is the first such method applicable to dynamic phospholipid lipidomic data. Our inference procedure closely fits experimental measurements and shows strong cross-validation across six independent experiments with distinct deuterium-labeled PE precursors, demonstrating the validity of our assumptions. In contrast, fits of randomized data or fits using random model parameters are worse. A key outcome is that we are able to robustly distinguish deacylation and reacylation kinetics of individual acyl chain types at the sn1 and sn2 positions, explaining the established prevalence of saturated and unsaturated chains in the respective positions. The present study thus demonstrates that dynamic acyl chain remodeling processes can be reliably determined from dynamic lipidomic data.

  4. Echocardiographic abnormalities in the assessment of cardiac organ damage in never-treated hypertensive patients.

    Science.gov (United States)

    Milan, Alberto; Avenatti, Eleonora; Puglisi, Elisabetta; Abram, Sara; Magnino, Corrado; Naso, Diego; Tosello, Francesco; Fabbri, Ambra; Vairo, Alessandro; Mulatero, Paolo; Rabbia, Franco; Veglio, Franco

    2012-01-01

    Hypertension-related cardiac organ damage, other than left ventricular (LV) hypertrophy (LVH), has been described: in particular, concentric remodeling, LV diastolic dysfunction (DD), and left atrial (LA) enlargement are significantly associated with cardiovascular morbility and mortality in different populations. This study evaluated the prevalence of these latter morphofunctional abnormalities, in never-treated essential hypertensive patients and the role of such a serial assessment of hypertensive cardiac damage in improving cardiovascular risk stratification in these patients. A total of 100 never-treated essential hypertensive subjects underwent a complete clinical and echocardiographic evaluation. Left ventricular morphology, systolic and diastolic function, and LA dimension (linear and volume) were evaluated by echocardiography. Left ventricular hypertrophy was present in 14% of the patients, whereas concentric remodeling was present in 25% of the subjects. Among patients free from LV morphology abnormalities, the most frequent abnormality was LA enlargement (global prevalence 57%); the percentage of patients with at least one parameter consistent with DD was 22% in the entire population, but DD was present as the only cardiac abnormality in 1% of our patient. Left atrial volume indexed for body surface area was the most sensitive parameter in identifying hypertension-related cardiac modification. The global prevalence of cardiac alteration reached 73% in never-treated hypertensive patients. Left ventricular remodeling and LA enlargement evaluation may grant a better assessment of cardiac organ damage and cardiovascular risk stratification of hypertensive patients without evidence of LVH after routine examination. PMID:22738434

  5. Immunologic and inflammatory mechanisms that drive asthma progression to remodeling

    OpenAIRE

    Broide, David H.

    2008-01-01

    Although histologic features of airway remodeling have been well characterized in asthma, the immunologic and inflammatory mechanisms that drive progression of asthma to remodeling are still incompletely understood. Conceptually, airway remodeling may be due to persistent inflammation and/or aberrant tissue repair mechanisms. It is likely that several immune and inflammatory cell types and mediators are involved in mediating airway remodeling. In addition, different features of airway remodel...

  6. TGF-beta, eosinophils and IL-13 in allergic airway remodeling: a critical appraisal with therapeutic considerations.

    Science.gov (United States)

    Fattouh, Ramzi; Jordana, Manel

    2008-12-01

    Airway remodeling is a characteristic feature of allergic asthma that is now thought to contribute to airway dysfunction and, ultimately, to clinical symptoms. A prevalent hypothesis holds that eosinophil-derived transforming growth factor-beta (TGF-beta) is a predominant underlying mechanism driving the development of remodeling and thus, represent promising targets for therapeutic intervention. This notion is supported by in vivo evidence from loss of function experiments conducted in animal models employing the surrogate allergen ovalbumin (OVA), and by indirect evidence from studies in human asthmatics. However, it is important to note that various studies in OVA systems have reported disconnects between eosinophils, TGF-beta and allergic remodeling. Moreover, recent investigations in a mouse model induced by respiratory exposure to a house dust mite extract have shown that remodeling can develop independently of TGF-beta. These findings challenge the above hypothesis and suggest that the mechanisms governing remodeling may be context specific. In addition to TGF-beta and eosinophils, several other factors have been implicated in the development of airway remodeling. Among these, interleukin (IL)-13 may be of particular importance given its role in type-2 immunity and in the tissue repair/fibrotic response. This review will appraise the evidence pertaining to the roles of TGF-beta, eosinophils and IL-13 in allergic remodeling, and will suggest that identifying robust targets for therapeutic intervention might benefit from a reconsideration of our approach to understanding remodeling. PMID:19075788

  7. Effects of candesartan on electrical remodeling in the hearts of inherited dilated cardiomyopathy model mice.

    Directory of Open Access Journals (Sweden)

    Fuminori Odagiri

    Full Text Available Inherited dilated cardiomyopathy (DCM is characterized by dilatation and dysfunction of the ventricles, and often results in sudden death or heart failure (HF. Although angiotensin receptor blockers (ARBs have been used for the treatment of HF, little is known about the effects on postulated electrical remodeling that occurs in inherited DCM. The aim of this study was to examine the effects of candesartan, one of the ARBs, on cardiac function and electrical remodeling in the hearts of inherited DCM model mice (TNNT2 ΔK210. DCM mice were treated with candesartan in drinking water for 2 months from 1 month of age. Control, non-treated DCM mice showed an enlargement of the heart with prolongation of QRS and QT intervals, and died at t1/2 of 70 days. Candesartan dramatically extended the lifespan of DCM mice, suppressed cardiac dilatation, and improved the functional parameters of the myocardium. It also greatly suppressed prolongation of QRS and QT intervals and action potential duration (APD in the left ventricular myocardium and occurrence of ventricular arrhythmia. Expression analysis revealed that down-regulation of Kv4.2 (Ito channel protein, KChIP2 (auxiliary subunit of Kv4.2, and Kv1.5 (IKur channel protein in DCM was partially reversed by candesartan administration. Interestingly, non-treated DCM heart had both normal-sized myocytes with moderately decreased Ito and IKur and enlarged cells with greatly reduced K+ currents (Ito, IKur IK1 and Iss. Treatment with candesartan completely abrogated the emergence of the enlarged cells but did not reverse the Ito, and IKur in normal-sized cells in DCM hearts. Our results indicate that candesartan treatment suppresses structural remodeling to prevent severe electrical remodeling in inherited DCM.

  8. A Computational Model for Simulating Spaceflight Induced Bone Remodeling

    Science.gov (United States)

    Pennline, James A.; Mulugeta, Lealem

    2014-01-01

    An overview of an initial development of a model of bone loss due to skeletal unloading in weight bearing sites is presented. The skeletal site chosen for the initial application of the model is the femoral neck region because hip fractures can be debilitating to the overall performance health of astronauts. The paper begins with the motivation for developing such a model of the time course of change in bone in order to understand the mechanism of bone demineralization experienced by astronauts in microgravity, to quantify the health risk, and to establish countermeasures. Following this, a general description of a mathematical formulation of the process of bone remodeling is discussed. Equations governing the rate of change of mineralized bone volume fraction and active osteoclast and osteoblast are illustrated. Some of the physiology of bone remodeling, the theory of how imbalance in remodeling can cause bone loss, and how the model attempts to capture this is discussed. The results of a preliminary validation analysis that was carried out are presented. The analysis compares a set of simulation results against bone loss data from control subjects who participated in two different bed rest studies. Finally, the paper concludes with outlining the current limitations and caveats of the model, and planned future work to enhance the state of the model.

  9. The SWI/SNF BAF-A complex is essential for neural crest development.

    Science.gov (United States)

    Chandler, Ronald L; Magnuson, Terry

    2016-03-01

    Growing evidence indicates that chromatin remodeler mutations underlie the pathogenesis of human neurocristopathies or disorders that affect neural crest cells (NCCs). However, causal relationships among chromatin remodeler subunit mutations and NCC defects remain poorly understood. Here we show that homozygous loss of ARID1A-containing, SWI/SNF chromatin remodeling complexes (BAF-A) in NCCs results in embryonic lethality in mice, with mutant embryos succumbing to heart defects. Strikingly, monoallelic loss of ARID1A in NCCs led to craniofacial defects in adult mice, including shortened snouts and low set ears, and these defects were more pronounced following homozygous loss of ARID1A, with the ventral cranial bones being greatly reduced in size. Early NCC specification and expression of the BRG1 NCC target gene, PLEXINA2, occurred normally in the absence of ARID1A. Nonetheless, mutant embryos displayed incomplete conotruncal septation of the cardiac outflow tract and defects in the posterior pharyngeal arteries, culminating in persistent truncus arteriosus and agenesis of the ductus arteriosus. Consistent with this, migrating cardiac NCCs underwent apoptosis within the circumpharyngeal ridge. Our data support the notion that multiple, distinct chromatin remodeling complexes govern genetically separable events in NCC development and highlight a potential pathogenic role for NCCs in the human BAF complex disorder, Coffin-Siris Syndrome. PMID:26806701

  10. Effect of Shenxinning decoction on ventricular remodeling in AT1 receptor-knockout mice with chronic renal insufficiency

    Directory of Open Access Journals (Sweden)

    Xuejun Yang

    2014-01-01

    Full Text Available Objective: To observe the efficacy of Shenxinning Decoction (SXND in ventricular remodeling in AT1 receptor-knockout (AT1-KO mice with chronic renal insufficiency (CRI. Materials and Methods: AT1-KO mice modeled with subtotal (5/6 nephrectomy were intervened with SXND for 12 weeks. Subsequently, blood urea nitrogen (BUN, serum creatinine (SCr, brain natriuretic peptide (BNP, echocardiography (left ventricular end-diastolic diameter, LVDD; left ventricular end-systolic diameter, LVDS; fractional shortening, FS; and ejection fraction, EF, collagen types I and III in the heart and kidney, myocardial mitochondria, and cardiac transforming growth factor-β1 (TGF-β1 of the AT1-KO mice were compared with the same model with nephrectomy only and untreated with SXND. Results: AT1-KO mice did not affect the process of CRI but it could significantly affect cardiac remodeling process. SXND decreased to some extent the AT1-KO mice′s BUN, SCr, BNP, and cardiac LVDD, LVDS, and BNP, improved FS and EF, lowered the expression of collagen type I and III in heart and kidney, increased the quantity of mitochondria and ameliorated their structure, and down-regulated the expression of TGF-β1. Conclusion: SXND may antagonize the renin-angiotensin system (RAS and decrease uremia toxins, thereby ameliorating ventricular remodeling in CRI. Furthermore, SXND has a mechanism correlated with the improvement of myocardial energy metabolism and the down-regulation of TGF-β1.

  11. Multi-factor analysis of failure of renal replacement therapy in acute renal failure developed after cardiac surgery

    Science.gov (United States)

    Szwedo, Ireneusz; Tyc, Joanna; Hawrysz, Anna; Janiak, Kamila; Cichoń, Romuald

    2015-01-01

    Introduction Acute renal failure (ARF) is a rare (2-15%), but severe complication of cardiac surgery with overall mortality reaching 40-80%. In order to save patients’ lives they are treated with renal replacement therapy (RRT). The aim of our study was to assess the impact of different perioperative factors on mortality among patients treated with RRT because of acute renal failure, which occurred as a complication of a heart surgery. Material and methods Retrospective analysis included 45 patients, operated in the years 2009-2013, who underwent renal replacement therapy in order to treat postoperative ARF. The perioperative factors were analysed in two groups: group 1 – patients who died before discharge; and group 2 – those who survived until hospital discharge. Results Forty-five of 3509 cardiac surgical patients (1.25%) required RRT after the surgery. A total of 23 (51.11%) died before discharge (group 1). Patients in group 1 were characterised by older age (70.21 vs. 67 years), higher mean EuroSCORE value (9.28 vs. 7.15) (p < 0.05), higher percentage of concomitant surgery (63.63% vs. 28.57%) (p < 0.05) and of admission of catecholamines in the postoperative period (100% vs. 68.42%) (p < 0.005), and higher mean urea blood level prior to RRT initiation (156.65 vs. 102.54 mg/dl) (p < 0.05). Conclusions The statistically relevant death predictors proved to be: high EuroSCORE, concomitant surgery, and high urea level at RRT initiation and admission of catecholamines in the postoperative period. After conformation in further studies, those factors may prove useful in stratification of death risk among surgical patients requiring RRT. PMID:26702273

  12. Surgical optimization and characterization of a minimally invasive aortic banding procedure to induce cardiac hypertrophy in mice.

    Science.gov (United States)

    Martin, Tamara P; Robinson, Emma; Harvey, Adam P; MacDonald, Margaret; Grieve, David J; Paul, Andrew; Currie, Susan

    2012-07-01

    Left ventricular pressure overload in response to aortic banding is an invaluable model for studying progression of cardiac hypertrophy and transition to heart failure. Traditional aortic banding has recently been superceded by minimally invasive transverse aortic banding (MTAB), which does not require ventilation so is less technically challenging. Although the MTAB approach is superior, few laboratories have documented success, and minimal information on the model is available. The aim of this study was to optimize conditions for MTAB and to characterize the development and progression of cardiac hypertrophy. Isofluorane proved the most suitable anaesthetic for MTAB surgery in mice, and 1 week after surgery the MTAB animals showed significant increases in systolic blood pressure (MTAB 110 ± 6 mmHg versus sham 78 ± 3 mmHg, n = 7, P MTAB 6.2 ± 0.2 versus sham 5.1 ± 0.1, n = 12, P MTAB 31.7 ± 1% versus sham 36.6 ± 1.4%, P = 0.01) and diastolic dysfunction (e.g. left ventricular end-diastolic pressure, MTAB 12.7 ± 1.0 mmHg versus sham 6.7 ± 0.8 mmHg, P MTAB hearts, signifying an inflammatory response. More pronounced remodelling was observed 4 weeks postsurgery (heart weight to body weight ratio, MTAB 9.1 ± 0.6 versus sham 4.6 ± 0.04, n = 10, P MTAB 24.3 ± 2.5% versus sham 43.6 ± 1.7%, n = 10, P = 0.003), together with a significant increase in cardiac fibrosis and further cardiac inflammation. Our findings demonstrate that MTAB is a relevant experimental model for studying development and progression of cardiac hypertrophy, which will be highly valuable for future studies examining potential novel therapeutic interventions in this setting. PMID:22447975

  13. Specification of the Cardiac Conduction System by Transcription Factors

    OpenAIRE

    Hatcher, Cathy J.; Basson, Craig T.

    2009-01-01

    Diseases of the cardiovascular system that cause sudden cardiac deaths are often caused by lethal arrhythmias that originate from defects in the cardiac conduction system. Development of the cardiac conduction system is a complex biological process that can be wrought with problems. Although several genes involved in mature conduction system function have been identified, their association with development of specific subcomponents of the cardiac conduction system remains challenging. Several...

  14. Cardiac perception and cardiac control. A review.

    Science.gov (United States)

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  15. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T;

    2015-01-01

    Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with...

  16. SERCA2a superinhibition by human phospholamban triggers electrical and structural remodeling in mouse hearts

    OpenAIRE

    Arvanitis, D. A.; Dong, M; E.G. Kranias; Lam, C. K.; Niklewski, P. J.; Sanoudou, D; Wang, H. -S.; Zhao, W

    2011-01-01

    Phospholamban (PLN), the reversible inhibitor of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), is a key regulator of myocyte Ca2+ cycling with a significant role in heart failure. We previously showed that the single amino acid difference between human and mouse PLN results in increased inhibition of Ca2+ cycling and cardiac remodeling and attenuated stress responses in transgenic mice expressing the human PLN (hPLN) in the null background. Here we dissect the molecular and electrop...

  17. The human tri-peptide GHK and tissue remodeling.

    Science.gov (United States)

    Pickart, Loren

    2008-01-01

    Tissue remodeling follows the initial phase of wound healing and stops inflammatory and scar-forming processes, then restores the normal tissue morphology. The human peptide Gly-(L-His)-(L-Lys) or GHK, has a copper 2+ (Cu(2+)) affinity similar to the copper transport site on albumin and forms GHK-Cu, a complex with Cu(2+). These two molecules activate a plethora of remodeling related processes: (1) chemoattraction of repair cells such as macrophages, mast cells, capillary cells; (2) anti-inflammatory actions (suppression of free radicals, thromboxane formation, release of oxidizing iron, transforming growth factor beta-1, tumor necrosis factor alpha and protein glycation while increasing superoxide dismutase, vessel vasodilation, blocking ultraviolet damage to skin keratinocytes and improving fibroblast recovery after X-ray treatments); (3) increases protein synthesis of collagen, elastin, metalloproteinases, anti-proteases, vascular endothelial growth factor, fibroblast growth factor 2, nerve growth factor, neutrotropins 3 and 4, and erythropoietin; (4) increases the proliferation of fibroblasts and keratinocytes; nerve outgrowth, angiogenesis, and hair follicle size. GHK-Cu stimulates wound healing in numerous models and in humans. Controlled studies on aged skin demonstrated that it tightens skin, improves elasticity and firmness, reduces fine lines, wrinkles, photodamage and hyperpigmentation. GHK-Cu also improves hair transplant success, protects hepatic tissue from tetrachloromethane poisoning, blocks stomach ulcer development, and heals intestinal ulcers and bone tissue. These results are beginning to define the complex biochemical processes that regulate tissue remodeling. PMID:18644225

  18. Quantitative computed tomography imaging of airway remodeling in severe asthma.

    Science.gov (United States)

    Grenier, Philippe A; Fetita, Catalin I; Brillet, Pierre-Yves

    2016-02-01

    Asthma is a heterogeneous condition and approximately 5-10% of asthmatic subjects have severe disease associated with structure changes of the airways (airway remodeling) that may develop over time or shortly after onset of disease. Quantitative computed tomography (QCT) imaging of the tracheobronchial tree and lung parenchyma has improved during the last 10 years, and has enabled investigators to study the large airway architecture in detail and assess indirectly the small airway structure. In severe asthmatics, morphologic changes in large airways, quantitatively assessed using 2D-3D airway registration and recent algorithms, are characterized by airway wall thickening, luminal narrowing and bronchial stenoses. Extent of expiratory gas trapping, quantitatively assessed using lung densitometry, may be used to assess indirectly small airway remodeling. Investigators have used these quantitative imaging techniques in order to attempt severity grading of asthma, and to identify clusters of asthmatic patients that differ in morphologic and functional characteristics. Although standardization of image analysis procedures needs to be improved, the identification of remodeling pattern in various phenotypes of severe asthma and the ability to relate airway structures to important clinical outcomes should help target treatment more effectively. PMID:26981458

  19. Remodeling of the methylation landscape in breast cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Marsha Reyngold

    Full Text Available The development of breast cancer metastasis is accompanied by dynamic transcriptome changes and dramatic alterations in nuclear and chromatin structure. The basis of these changes is incompletely understood. The DNA methylome of primary breast cancers contribute to transcriptomic heterogeneity and different metastatic behavior. Therefore we sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome and transcriptome of 44 matched primary breast tumors and regional metastases. Striking subtype-specific patterns of metastasis-associated methylome remodeling were observed, which reflected the molecular heterogeneity of breast cancers. These divergent changes occurred primarily in CpG island (CGI-poor areas. Regions of methylome reorganization shared by the subtypes were also observed, and we were able to identify a metastasis-specific methylation signature that was present across the breast cancer subclasses. These alterations also occurred outside of CGIs and promoters, including sequences flanking CGIs and intergenic sequences. Integrated analysis of methylation and gene expression identified genes whose expression correlated with metastasis-specific methylation. Together, these findings significantly enhance our understanding of the epigenetic reorganization that occurs during regional breast cancer metastasis across the major breast cancer subtypes and reveal the nature of methylome remodeling during this process.

  20. Hyperhomocysteinemia promotes vascular remodeling in vein graph in mice.

    Science.gov (United States)

    Tan, Hongmei; Shi, Chengwei; Jiang, Xiaohua; Lavelle, Muriel; Yu, Caijia; Yang, Xiaofeng; Wang, Hong

    2014-01-01

    This study investigated the role and mechanism of Hyperhomocysteinemia (HHcy) on vascular remodeling in mice. We assessed the effect of HHcy on vascular remodeling using a carotid arterial vein patch model in mice with the gene deletion of cystathionine-beta-synthase (Cbs). Vein grafts were harvested 4 weeks after surgery. Cross sections were analyzed using Verhoeff-van Gieson staining, Masson`s Trichrome staining, and immunostaining for morphological analysis and protein level assessment. The effect of Hcy on collagen secretion was examined in cultured rat aortic smooth muscle cells (RASMC). We found that Cbs-/- mice with severe HHcy exhibited thicker neointima and a higher percentage of luminal narrowing in vein grafts. In addition, severe HHcy increased elastin and collagen deposition in the neointima. Further, severe HHcy increases CD45 positive cells and proliferative cells in vein grafts. Finally, Hcy increases collagen secretion in RASMC. These results demonstrate that HHcy increases neointima formation, elastin and collagen deposition following a carotid arterial vein patch. The capacity of Hcy to promote vascular fibrosis and inflammation may contribute to the development of vascular remodeling. PMID:24896329

  1. Galectin-3 inhibition prevents adipose tissue remodelling in obesity.

    Science.gov (United States)

    Martínez-Martínez, E; Calvier, L; Rossignol, P; Rousseau, E; Fernández-Celis, A; Jurado-López, R; Laville, M; Cachofeiro, V; López-Andrés, N

    2016-06-01

    Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg(-1) per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10(-8 )m) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity. PMID:26853916

  2. Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice.

    Science.gov (United States)

    Merentie, Mari; Lipponen, Jukka A; Hedman, Marja; Hedman, Antti; Hartikainen, Juha; Huusko, Jenni; Lottonen-Raikaslehto, Line; Parviainen, Viktor; Laidinen, Svetlana; Karjalainen, Pasi A; Ylä-Herttuala, Seppo

    2015-12-01

    Mouse models are extremely important in studying cardiac pathologies and related electrophysiology, but very few mouse ECG analysis programs are readily available. Therefore, a mouse ECG analysis algorithm was developed and validated. Surface ECG (lead II) was acquired during transthoracic echocardiography from C57Bl/6J mice under isoflurane anesthesia. The effect of aging was studied in young (2-3 months), middle-aged (14 months) and old (20-24 months) mice. The ECG changes associated with pharmacological interventions and common cardiac pathologies, that is, acute myocardial infarction (AMI) and progressive left ventricular hypertrophy (LVH), were studied. The ECG raw data were analyzed with an in-house ECG analysis program, modified specially for mouse ECG. Aging led to increases in P-wave duration, atrioventricular conduction time (PQ interval), and intraventricular conduction time (QRS complex width), while the R-wave amplitude decreased. In addition, the prevalence of arrhythmias increased during aging. Anticholinergic atropine shortened PQ time, and beta blocker metoprolol and calcium-channel blocker verapamil increased PQ interval and decreased heart rate. The ECG changes after AMI included early JT elevation, development of Q waves, decreased R-wave amplitude, and later changes in JT/T segment. In progressive LVH model, QRS complex width was increased at 2 and especially 4 weeks timepoint, and also repolarization abnormalities were seen. Aging, drugs, AMI, and LVH led to similar ECG changes in mice as seen in humans, which could be reliably detected with this new algorithm. The developed method will be very useful for studies on cardiovascular diseases in mice. PMID:26660552

  3. Acute cardiac failure in neuroleptic malignant syndrome.

    LENUS (Irish Health Repository)

    Sparrow, Patrick

    2012-02-03

    We present a case of rapid onset acute cardiac failure developing as part of neuroleptic malignant syndrome in a 35-year-old woman following treatment with thioridazine and lithium. Post mortem histology of cardiac and skeletal muscle showed similar changes of focal cellular necrosis and vacuolation suggesting a common disease process.

  4. Inhaled tolafentrine reverses pulmonary vascular remodeling via inhibition of smooth muscle cell migration

    Directory of Open Access Journals (Sweden)

    Weissmann Norbert

    2005-11-01

    Full Text Available Abstract Background The aim of the study was to assess the chronic effects of combined phosphodiesterase 3/4 inhibitor tolafentrine, administered by inhalation, during monocrotaline-induced pulmonary arterial hypertension (PAH in rats. Methods CD rats were given a single subcutaneous injection of monocrotaline to induce PAH. Four weeks after, rats were subjected to inhalation of tolafentrine or sham nebulization in an unrestrained, whole body aerosol exposure system. In these animals (i the acute pulmonary vasodilatory efficacy of inhaled tolafentrine (ii the anti-remodeling effect of long-term inhalation of tolafentrine (iii the effects of tolafentrine on the expression profile of 96 genes encoding cell adhesion and extracellular matrix regulation were examined. In addition, the inhibitory effect of tolafentrine on ex vivo isolated pulmonary artery SMC cell migration was also investigated. Results Monocrotaline injection provoked severe PAH (right ventricular systolic pressure increased from 25.9 ± 4.0 to 68.9 ± 3.2 after 4 weeks and 74.9 ± 5.1 mmHg after 6 weeks, cardiac output depression and right heart hypertrophy. The media thickness of the pulmonary arteries and the proportion of muscularization of small precapillary resistance vessels increased dramatically, and the migratory response of ex-vivo isolated pulmonary artery smooth muscle cells (PASMC was increased. Micro-arrays and subsequent confirmation with real time PCR demonstrated upregulation of several extracellular matrix regulation and adhesion genes, such as matrixmetalloproteases (MMP 2, 8, 9, 10, 11, 12, 20, Icam, Itgax, Plat and serpinb2. When chronically nebulized from day 28 to 42 (12 daily aerosol maneuvers, after full establishment of severe pulmonary hypertension, tolafentrine reversed about 60% of all hemodynamic abnormalities, right heart hypertrophy and monocrotaline-induced structural lung vascular changes, including the proportion of pulmonary artery

  5. A remodelling metric for angular fibre distributions and its application to diseased carotid bifurcations.

    LENUS (Irish Health Repository)

    Creane, Arthur

    2012-07-01

    Many soft biological tissues contain collagen fibres, which act as major load bearing constituents. The orientation and the dispersion of these fibres influence the macroscopic mechanical properties of the tissue and are therefore of importance in several areas of research including constitutive model development, tissue engineering and mechanobiology. Qualitative comparisons between these fibre architectures can be made using vector plots of mean orientations and contour plots of fibre dispersion but quantitative comparison cannot be achieved using these methods. We propose a \\'remodelling metric\\' between two angular fibre distributions, which represents the mean rotational effort required to transform one into the other. It is an adaptation of the earth mover\\'s distance, a similarity measure between two histograms\\/signatures used in image analysis, which represents the minimal cost of transforming one distribution into the other by moving distribution mass around. In this paper, its utility is demonstrated by considering the change in fibre architecture during a period of plaque growth in finite element models of the carotid bifurcation. The fibre architecture is predicted using a strain-based remodelling algorithm. We investigate the remodelling metric\\'s potential as a clinical indicator of plaque vulnerability by comparing results between symptomatic and asymptomatic carotid bifurcations. Fibre remodelling was found to occur at regions of plaque burden. As plaque thickness increased, so did the remodelling metric. A measure of the total predicted fibre remodelling during plaque growth, TRM, was found to be higher in the symptomatic group than in the asymptomatic group. Furthermore, a measure of the total fibre remodelling per plaque size, TRM\\/TPB, was found to be significantly higher in the symptomatic vessels. The remodelling metric may prove to be a useful tool in other soft tissues and engineered scaffolds where fibre adaptation is also present.

  6. Wnt Signalling Promotes Actin Dynamics during Axon Remodelling through the Actin-Binding Protein Eps8.

    Directory of Open Access Journals (Sweden)

    Eleanna Stamatakou

    Full Text Available Upon arrival at their synaptic targets, axons slow down their growth and extensively remodel before the assembly of presynaptic boutons. Wnt proteins are target-derived secreted factors that promote axonal remodelling and synaptic assembly. In the developing spinal cord, Wnts secreted by motor neurons promote axonal remodelling of NT-3 responsive dorsal root ganglia neurons. Axon remodelling induced by Wnts is characterised by growth cone pausing and enlargement, processes that depend on the re-organisation of microtubules. However, the contribution of the actin cytoskeleton has remained unexplored. Here, we demonstrate that Wnt3a regulates the actin cytoskeleton by rapidly inducing F-actin accumulation in growth cones from rodent DRG neurons through the scaffold protein Dishevelled-1 (Dvl1 and the serine-threonine kinase Gsk3β. Importantly, these changes in actin cytoskeleton occurs before enlargement of the growth cones is evident. Time-lapse imaging shows that Wnt3a increases lamellar protrusion and filopodia velocity. In addition, pharmacological inhibition of actin assembly demonstrates that Wnt3a increases actin dynamics. Through a yeast-two hybrid screen, we identified the actin-binding protein Eps8 as a direct interactor of Dvl1, a scaffold protein crucial for the Wnt signalling pathway. Gain of function of Eps8 mimics Wnt-mediated axon remodelling, whereas Eps8 silencing blocks the axon remodelling activity of Wnt3a. Importantly, blockade of the Dvl1-Eps8 interaction completely abolishes Wnt3a-mediated axonal remodelling. These findings demonstrate a novel role for Wnt-Dvl1 signalling through Eps8 in the regulation of axonal remodeling.

  7. Cardiac tissue engineering in magnetically actuated scaffolds

    International Nuclear Information System (INIS)

    Cardiac tissue engineering offers new possibilities for the functional and structural restoration of damaged or lost heart tissue by applying cardiac patches created in vitro. Engineering such functional cardiac patches is a complex mission, involving material design on the nano- and microscale as well as the application of biological cues and stimulation patterns to promote cell survival and organization into a functional cardiac tissue. Herein, we present a novel strategy for creating a functional cardiac patch by combining the use of a macroporous alginate scaffold impregnated with magnetically responsive nanoparticles (MNPs) and the application of external magnetic stimulation. Neonatal rat cardiac cells seeded within the magnetically responsive scaffolds and stimulated by an alternating magnetic field of 5 Hz developed into matured myocardial tissue characterized by anisotropically organized striated cardiac fibers, which preserved its features for longer times than non-stimulated constructs. A greater activation of AKT phosphorylation in cardiac cell constructs after applying a short-term (20 min) external magnetic field indicated the efficacy of magnetic stimulation to actuate at a distance and provided a possible mechanism for its action. Our results point to a synergistic effect of magnetic field stimulation together with nanoparticulate features of the scaffold surface as providing the regenerating environment for cardiac cells driving their organization into functionally mature tissue. (paper)

  8. Electrical stunning and hibernation: suggestion of new terms for short- and long-term cardiac memory.

    Science.gov (United States)

    Zoghi, Mehdi; Nalbantgil, Sanem

    2004-09-01

    Persistent T wave changes following resumption of sinus rhythm induced by pacing or arrhythmias that cause altering of ventricular activation sequence are named "cardiac memory". After this initial definition there has been a discussion whether such T wave changes are primary, secondary or pseudoprimary. In addition according to the results of pathophysiological studies investigating the mechanism and nature of this repolarization abnormality some authors have preferred to use the term "electrical remodelling" instead of cardiac memory. But these two terms are still not well defined. In this article, the previous terms are discussed and a new term instead of cardiac memory is introduced. PMID:15294266

  9. What Is Cardiac Rehabilitation?

    Science.gov (United States)

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  10. Ataxia telangiectasia-mutated kinase deficiency exacerbates left ventricular dysfunction and remodeling late after myocardial infarction.

    Science.gov (United States)

    Daniel, Laura L; Scofield, Stephanie L C; Thrasher, Patsy; Dalal, Suman; Daniels, Christopher R; Foster, Cerrone R; Singh, Mahipal; Singh, Krishna

    2016-08-01

    Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3β (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy. PMID:27288435

  11. A Puzzle Used to Teach the Cardiac Cycle

    Science.gov (United States)

    Marcondes, Fernanda K.; Moura, Maria J. C. S.; Sanches, Andrea; Costa, Rafaela; Oliveira de Lima, Patricia; Groppo, Francisco Carlos; Amaral, Maria E. C.; Zeni, Paula; Gaviao, Kelly Cristina; Montrezor, Luís H.

    2015-01-01

    The aim of the present article is to describe a puzzle developed for use in teaching cardiac physiology classes. The puzzle presents figures of phases of the cardiac cycle and a table with five columns: phases of cardiac cycle, atrial state, ventricular state, state of atrioventricular valves, and pulmonary and aortic valves. Chips are provided…

  12. Diffuse infiltrative cardiac tuberculosis

    International Nuclear Information System (INIS)

    We present the cardiac magnetic resonance images of an unusual form of cardiac tuberculosis. Nodular masses in a sheet-like distribution were seen to infiltrate the outer myocardium and pericardium along most of the cardiac chambers. The lesions showed significant resolution on antitubercular therapy

  13. Myocardial stunning after resuscitation from cardiac arrest following spinal anaesthesia

    OpenAIRE

    Pranjali Madhav Kurhekar; VSG Yachendra; Simi P Babu; Raghavelu Govindasamy

    2014-01-01

    Cardiac arrest associated with spinal anaesthesia has been well researched. Myocardial stunning after successful resuscitation from cardiac arrest is seen in up to 2/3 rd of in-hospital cardiac arrests. Myocardial stunning after resuscitation from cardiac arrest associated with spinal anaesthesia has probably not been reported earlier. Our case, an ASA physical status I lady, posted for tubal reanastomosis surgery developed bradycardia followed by asystole, approximately 5 minutes after givin...

  14. Microcirculatory remodeling in marginal zone of duodenal ulcer after bleeding

    Directory of Open Access Journals (Sweden)

    Sulayeva О.N.

    2009-01-01

    Full Text Available To estimate objectively vessels network remodeling in duodenal mucosa after ulcer bleeding the morphometric analysis of marginal ulcer zone biopsies was performed in 32 patients. It was shown that reparation is accompanied with chronic inflammation and acute alteration of microcirculation. Injection hemostasis led to enhancement of microcirculation, development of edema and ischemic alteration of mucosal tissues. Acute neutrophilic infiltration during 1 day was changed on 3 day with granular tissue development and angiogenesis stimulation. Intensification and prolongation of angiogenesis paral-leled with lymphocytes infiltration after 7 days resulted to villi dysmorphogenesis and changes in cellular content of intestinal epithelium.

  15. Cardiac Abnormalities in Youth with Obesity and Type 2 Diabetes.

    Science.gov (United States)

    Bacha, Fida; Gidding, Samuel S

    2016-07-01

    Childhood obesity has been linked to cardiovascular disease (CVD) risk in adulthood. Of great concern is the expected increase in the population's CVD burden in relation to childhood obesity. This is compounded by the risk related to chronic hyperglycemia exposure in youth with type 2 diabetes. We herein provide an overview of the spectrum of early cardiovascular disease manifestation in youth with obesity and type 2 diabetes, in particular abnormalities in cardiac structure and function. Cardiac remodeling and adverse target organ damage is already evident in the pediatric age group in children with obesity and type 2 diabetes. This supports the importance of intensifying obesity prevention efforts and early intervention to treat comorbidities of obesity in the pediatric age group to prevent cardiac events in early adulthood. PMID:27168062

  16. Observations of super early left ventricular remodeling experimental myocardial infarction

    International Nuclear Information System (INIS)

    Purpose: Ventricular remodeling is defined as the changes in the shape and size of the entire left ventricle after acute myocardial infarction (AMI). Many investigators have shown that left ventricular remodeling is related to clinical outcomes, including mortality, that represent the natural history, of the heart failure syndrome. The aim of this study was to demonstrate that it is possible to observe super early left ventricular remodeling by 99mTc-MIBI myocardial imaging in the dog model of acute experimental myocardial infarction. Methods: Experimental subjects: Twenty-three healthy mongrel dogs (14-25 kg) of either sex were studied under general anesthesia (sodium pentobarbital, 30 mg/kg). The left anterior descending (LAD) coronary artery was dissected and ligated between the first and second diagonal branches. Seven dogs died of ventricular fibrillation after the LAD coronary artery ligation. The 16 remaining dogs were divided into two groups: Group A (GA) received 99mTc-MIBI myocardial imaging (n=8): Group B (GB) received 99mTc-MIBI myocardial imaging combined with echocardiography (n=8). 99mTc-MIBI myocardial perfusion imaging :Static 99mTc-MIBI myocardial imaging was taken with ADAC Vertex Dual-head SPECT. 99mTc-MIBI kit was manufactured in Syncor, China. Each dog served as its own control, and was scanned by 99mTc-MIBI myocardial imaging and chocardiography at 48-72 hours before ligation. The mean time of the first acquisition was 21.87 ± 11.03 (14-48) minutes post-operatively in GA, 57.63±22.83 (30-99) minutes for 99mTc-MIBI imaging in GB, 26.00±15.07 (12-50) minutes for echocardiography in GB. Acquisition techniques for Gated SPECT: ECG synchronized data collection: R wave trigger, 8 Frames/Cardiac cycle. Images were gathered by rotating the detectors 180 degrees at 6 degrees per frame. Each frame took 40 seconds. The dog position was supine. The images were acquired and recorded for 6 hours following the LAD coronary artery ligation. After 6 hours

  17. A gene-centric study of common carotid artery remodelling

    Science.gov (United States)

    Harrison, Seamus C.; Zabaneh, Delilah; Asselbergs, Folkert W.; Drenos, Fotios; Jones, Gregory T.; Shah, Sonia; Gertow, Karl; Sennblad, Bengt; Strawbridge, Rona J.; Gigante, Bruna; Holewijn, Suzanne; De Graaf, Jacqueline; Vermeulen, Sita; Folkersen, Lasse; van Rij, Andre M.; Baldassarre, Damiano; Veglia, Fabrizio; Talmud, Philippa J.; Deanfield, John E.; Agu, Obi; Kivimaki, Mika; Kumari, Meena; Bown, Matthew J.; Nyyssönen, Kristiina; Rauramaa, Rainer; Smit, Andries J.; Franco-Cereceda, Anders; Giral, Philippe; Mannarino, Elmo; Silveira, Angela; Syvänen, Ann-Christine; de Borst, Gert J.; van der Graaf, Yolanda; de Faire, Ulf; Baas, Annette F.; Blankensteijn, Jan D.; Wareham, Nicholas J.; Fowkes, Gerry; Tzoulaki, Ionna; Price, Jacqueline F.; Tremoli, Elena; Hingorani, Aroon D.; Eriksson, Per; Hamsten, Anders; Humphries, Steve E.

    2013-01-01

    Background Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. Methods Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA). Results rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08–0.18 mm, P = 8.2 × 10−8). A proxy SNP (rs4916251, R2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case–control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03–1.17, p = 2.8 × 10−3, I2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling. Conclusions Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development. PMID:23246012

  18. Robust algorithmic detection of the developed cardiac pathologies and emerging or transient abnormalities from short periods of RR data

    Science.gov (United States)

    Gavrishchaka, Valeriy V.; Senyukova, Olga

    2011-06-01

    Numerous research efforts and clinical testing have confirmed validity of heart rate variability (HRV) analysis as one of the cardiac diagnostics modalities. The majority of HRV analysis tools currently used in practice are based on linear indicators. Methods from nonlinear dynamics (NLD) provide more natural modeling framework for adaptive biological systems with multiple feedback loops. Compared to linear indicators, many NLD-based measures are much less sensitive to data artifacts and non-stationarity. However, majority of NLD measures require long time series for stable calculation. Similar restrictions also apply for linear indicators. Such requirements could drastically limit practical usability of HRV analysis in many applications, including express diagnostics, early indication of subtle directional changes during personalization of medical treatment, and robust detection of emerging or transient abnormalities. Recently we have illustrated that these challenges could be overcome by using classification framework based on boosting-like ensemble learning techniques that are capable of discovering robust meta-indicators from existing HRV measures and other incomplete empirical knowledge. In this paper we demonstrate universality of such meta-indicators and discuss operational details of their practical usage. Using such pathology examples as congestive heart failure (CHF) and arrhythmias, we show that classifiers trained on short RR segments (down to several minutes) could achieve reasonable classification accuracy (˜80-85% and higher). These indicators calculated from longer RR segments could be applicable for accurate diagnostics with classification accuracy approaching 100%. In addition, it is feasible to discover single "normal-abnormal" meta-classifier capable of detecting multiple abnormalities.

  19. Development of endothermy and concomitant increases in cardiac and skeletal muscle mitochondrial respiration in the precocial Pekin duck (Anas platyrhynchos domestica).

    Science.gov (United States)

    Sirsat, Sarah K G; Sirsat, Tushar S; Faber, Alan; Duquaine, Allison; Winnick, Sarah; Sotherland, Paul R; Dzialowski, Edward M

    2016-04-15

    Attaining endothermic homeothermy occurs at different times post-hatching in birds and is associated with maturation of metabolic and aerobic capacity. Simultaneous measurements at the organism, organ and cellular levels during the transition to endothermy reveal means by which this change in phenotype occurs. We examined development of endothermy in precocial Pekin ducks ( ITALIC! Anas platyrhynchos domestica) by measuring whole-animal O2consumption ( ITALIC! V̇O2 ) as animals cooled from 35 to 15°C. We measured heart ventricle mass, an indicator of O2delivery capacity, and mitochondrial respiration in permeabilized skeletal and cardiac muscle to elucidate associated changes in mitochondrial capacities at the cellular level. We examined animals on day 24 of incubation through 7 days post-hatching. ITALIC! V̇O2  of embryos decreased when cooling from 35 to 15°C; ITALIC! V̇O2  of hatchlings, beginning on day 0 post-hatching, increased during cooling with a lower critical temperature of 32°C. Yolk-free body mass did not change between internal pipping and hatching, but the heart and thigh skeletal muscle grew at faster rates than the rest of the body as the animals transitioned from an externally pipped paranate to a hatchling. Large changes in oxidative phosphorylation capacity occurred during ontogeny in both thigh muscles, the primary site of shivering, and cardiac ventricles. Thus, increased metabolic capacity necessary to attain endothermy was associated with augmented metabolic capacity of the tissue and augmented increasing O2delivery capacity, both of which were attained rapidly at hatching. PMID:26896549

  20. Exercise, Nrf2 and Antioxidant Signaling in Cardiac Aging.

    Science.gov (United States)

    Narasimhan, Madhusudhanan; Rajasekaran, Namakkal S

    2016-01-01

    Aging is represented by a progressive decline in cellular functions. The age-related deformities in cardiac behaviors are the loss of cardiac myocytes through apoptosis or programmed cell death. Oxidative stress (OS) and its deleterious consequence contribute to age-related mechanical remodeling, reduced regenerative capacity, and apoptosis in cardiac tissue. The pathogenesis of OS in the elderly can predispose the heart to other cardiac complications such as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and so on. At the molecular level, oxidant-induced activation of Nrf2 (Nuclear erythroid-2-p45-related factor-2), a transcription factor, regulates several genes containing AREs (Antioxidant Response Element) and bring the respective translates to counteract the reactive radicals and establish homeostasis. Myriad of Nrf2 gene knockout studies in various organs such as lung, liver, kidney, brain, etc. have shown that dysregulation of Nrf2 severely affects the oxidant/ROS sensitivity and predispose the system to several pathological changes with aberrant cellular lesions. On the other hand, its gain of function chemical interventions exhibited oxidant stress resistance and cytoprotection. However, thus far, only a few investigations have shown the potential role of Nrf2 and its non-pharmacological induction in cardiac aging. Therefore, here we review the involvement of Nrf2 signaling along with its responses and ramifications on the cascade of OS under acute exercise stress (AES), moderate exercise training (MET), and endurance exercise stress (EES) conditions in the aging heart. PMID:27378947

  1. Performance Requirements on Remodeling Apartment Housing and TOPSIS Evaluation

    OpenAIRE

    Jaeho Cho; Jaeyoul Chun

    2015-01-01

    Functional improvement needed in remodeling projects is determined by users in a complex manner since remodeling projects require performance improvement against deterioration. This study defines fundamental Remodeling Performance Criteria (RPC) for apartment housing by referring to performance criteria of both domestic and international performance-related systems. In this case study, performance evaluation of Construction Element Method (CEM) for remodeling projects was conducted based on R...

  2. New predictive model for monitoring bone remodeling

    Czech Academy of Sciences Publication Activity Database

    Bougherara, H.; Klika, Václav; Maršík, František; Mařík, I.; Yahia, L.H.

    95A, č. 1 (2010), s. 9-24. ISSN 1549-3296 R&D Projects: GA ČR GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : bone remodeling * open system thermodynamics * bone biochemistry Subject RIV: BJ - Thermodynamics Impact factor: 3.044, year: 2010

  3. Link between vitamin D and airway remodeling

    Directory of Open Access Journals (Sweden)

    Berraies A

    2014-04-01

    Full Text Available Anissa Berraies, Kamel Hamzaoui, Agnes HamzaouiPediatric Respiratory Diseases Department, Abderrahmen Mami Hospital, Ariana, and Research Unit 12SP15 Tunis El Manar University, Tunis, TunisiaAbstract: In the last decade, many epidemiologic studies have investigated the link between vitamin D deficiency and asthma. Most studies have shown that vitamin D deficiency increases the risk of asthma and allergies. Low levels of vitamin D have been associated with asthma severity and loss of control, together with recurrent exacerbations. Remodeling is an early event in asthma described as a consequence of production of mediators and growth factors by inflammatory and resident bronchial cells. Consequently, lung function is altered, with a decrease in forced expiratory volume in one second and exacerbated airway hyperresponsiveness. Subepithelial fibrosis and airway smooth muscle cell hypertrophy are typical features of structural changes in the airways. In animal models, vitamin D deficiency enhances inflammation and bronchial anomalies. In severe asthma of childhood, major remodeling is observed in patients with low vitamin D levels. Conversely, the antifibrotic and antiproliferative effects of vitamin D in smooth muscle cells have been described in several experiments. In this review, we briefly summarize the current knowledge regarding the relationship between vitamin D and asthma, and focus on its effect on airway remodeling and its potential therapeutic impact for asthma.Keywords: vitamin D, asthma, airway remodeling, airway smooth muscle, supplementation

  4. Interleukin-20 promotes airway remodeling in asthma.

    Science.gov (United States)

    Gong, Wenbin; Wang, Xin; Zhang, Yuguo; Hao, Junqing; Xing, Chunyan; Chu, Qi; Wang, Guicheng; Zhao, Jiping; Wang, Junfei; Dong, Qian; Liu, Tian; Zhang, Yuanyuan; Dong, Liang

    2014-12-01

    Previous studies have demonstrated that interleukin-20 (IL-20) is a pro-inflammatory cytokine, and it has been implicated in psoriasis, lupus nephritis, rheumatoid arthritis, atherosclerosis, and ulcerative colitis. Little is known about the effects of IL-20 in airway remodeling in asthma. The aim of our study was to demonstrate the function of IL-20 in airway remodeling in asthma. To identify the expression of IL-20 and its receptor, IL-20R1/IL-20R2, in the airway epithelium in bronchial tissues, bronchial biopsy specimens were collected from patients and mice with asthma and healthy subjects and stained with specific antibodies. To characterize the effects of IL-20 in asthmatic airway remodeling, we silenced and stimulated IL-20 in cell lines isolated from mice by shRNA and recombinant protein approaches, respectively, and detected the expression of α-SMA and FN-1 by Western blot analysis. First, overexpression of IL-20 and its receptor, IL-20R1/IL-20R2, was detected in the airway epithelium collected from patients and mice with asthma. Second, IL-20 increased the expression of fibronectin-1 and α-SMA, and silencing of IL-20 in mouse lung epithelial (MLE)-12 cells decreased the expression of fibronectin-1 and α-SMA. IL-20 may be a critical cytokine in airway remodeling in asthma. This study indicates that targeting IL-20 and/or its receptors may be a new therapeutic strategy for asthma. PMID:25028099

  5. Remodelling of flash furnace for coal firing

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Z.

    1982-05-01

    The Chichiku Cement Co. has succeeded in re-converting all its cement plants from oil to coal firing system with no impairment at all to production rate or to unit energy consumption. The reconversion wea achieved by remodelling four of its five principal kilns from a system of suspension preheater with calciner to the C-SF kiln system.

  6. MYOCARDIAL REMODELING IN ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    A. N. Zakirova

    2016-01-01

    Full Text Available Aim. To study the myocardial remodeling features in patients with stable angina depending on disease severity and experienced myocardial infarction (MI.Material and methods. 148 male patients with stable angina were examined and randomized into 3 groups (G1-G3. 52 patients of G1 had angina of I-II functional class (FC. 49 patients of G2 had angina of III FC, and 47 patients of G3 had angina of IV FC. History of MI had 79,5, 87.2 and 92.6% of patients in G1, G2 and G3 respectively. 35 healthy men were included into control group. Coronarography, bicycle ergometry and 24-hour ECG monitoring was performed. Left ventricular (LV function and remodeling was assessed with echocardiography.Results. G3 patients had LV eccentric hypertrophy as a result of postinfarction cardiosclerosis which accompanied with LV systolic dysfunction, a myocardial stress increasing and LV spherification. G1 patients had no any significant disorders of LV systolic function.Conclusion. Severe ischemic heart disease is associated with a dysadaptive remodeling unlike mild ischemic heart disease, which is associated with an adaptive myocardial remodeling.

  7. Re-Modelling as De-Professionalisation

    Science.gov (United States)

    Thompson, Meryl

    2006-01-01

    The article sets out the consequences of the British Government's remodelling agenda and its emphasis on less demarcation, for the professional status of teachers in England. It describes how the National Agreement on Raising Standards and Tackling Workload, reached between five of the six trade unions for teachers and headteachers paves the way…

  8. Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction

    OpenAIRE

    Ayach, Bilal B.; Yoshimitsu, Makoto; Dawood, Fayez; Sun, Mei; Arab, Sara; Chen, Manyin; HIGUCHI, KOJI; Siatskas, Christopher; Lee, Paul; Lim, Hilda; Zhang, Jane; Cukerman, Eva; Stanford, William L.; Medin, Jeffrey A; Liu, Peter P.

    2006-01-01

    Inappropriate cardiac remodeling and repair after myocardial infarction (MI) predisposes to heart failure. Studies have reported on the potential for lineage negative, steel factor positive (c-kit+) bone marrow-derived hematopoetic stem∕progenitor cells (HSPCs) to repair damaged myocardium through neovascularization and myogenesis. However, the precise contribution of the c-kit signaling pathway to the cardiac repair process has yet to be determined. In this study, we sought to directly eluci...

  9. Plasma tissue inhibitor of matrix metalloproteinase-1 (TIMP-1): an independent predictor of poor response to cardiac resynchronization therapy

    OpenAIRE

    Tolosana, Jose María; Mont, Lluís; Sitges, Marta; Berruezo, Antonio; Delgado, Victoria; Vidal, Bàrbara; Tamborero, David; Morales, Manel; Batlle, Montserrat; Roig, Eulalia; Castel, M. Angeles; Pérez-Villa, Félix; Godoy, Miguel; Brugada, Josep

    2010-01-01

    Aims Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular structural remodelling. The aim of our study was to analyse MMP-2 and TIMP-1 levels as predictors of poor response to cardiac resynchronization therapy (CRT). Methods and results A cohort of 42 CRT patients from our centre was prospectively evaluated at baseline and after 12-month follow-up. MMP-2 and TIMP-1 assays were performed prior to CRT implant. Cardiac resynchronization therapy res...

  10. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    Science.gov (United States)

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function. PMID:26612091

  11. Cardiac tumours in children

    Directory of Open Access Journals (Sweden)

    Parsons Jonathan M

    2007-03-01

    Full Text Available Abstract Cardiac tumours are benign or malignant neoplasms arising primarily in the inner lining, muscle layer, or the surrounding pericardium of the heart. They can be primary or metastatic. Primary cardiac tumours are rare in paediatric practice with a prevalence of 0.0017 to 0.28 in autopsy series. In contrast, the incidence of cardiac tumours during foetal life has been reported to be approximately 0.14%. The vast majority of primary cardiac tumours in children are benign, whilst approximately 10% are malignant. Secondary malignant tumours are 10–20 times more prevalent than primary malignant tumours. Rhabdomyoma is the most common cardiac tumour during foetal life and childhood. It accounts for more than 60% of all primary cardiac tumours. The frequency and type of cardiac tumours in adults differ from those in children with 75% being benign and 25% being malignant. Myxomas are the most common primary tumours in adults constituting 40% of benign tumours. Sarcomas make up 75% of malignant cardiac masses. Echocardiography, Computing Tomography (CT and Magnetic Resonance Imaging (MRI of the heart are the main non-invasive diagnostic tools. Cardiac catheterisation is seldom necessary. Tumour biopsy with histological assessment remains the gold standard for confirmation of the diagnosis. Surgical resection of primary cardiac tumours should be considered to relieve symptoms and mechanical obstruction to blood flow. The outcome of surgical resection in symptomatic, non-myxomatous benign cardiac tumours is favourable. Patients with primary cardiac malignancies may benefit from palliative surgery but this approach should not be recommended for patients with metastatic cardiac tumours. Surgery, chemotherapy and radiotherapy may prolong survival. The prognosis for malignant primary cardiac tumours is generally extremely poor.

  12. Time course of infarct healing and left ventricular remodelling in patients with reperfused ST segment elevation myocardial infarction using comprehensive magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ganame, Javier [University Hospitals Leuven, Cardiology Department, Leuven (Belgium); University Hospitals Leuven, Radiology Department, Leuven (Belgium); Messalli, Giancarlo; Dymarkowski, Steven; Abbasi, Kayvan; Bogaert, Jan [University Hospitals Leuven, Radiology Department, Leuven (Belgium); Masci, Pier Giorgio [University Hospitals Leuven, Radiology Department, Leuven (Belgium); MRI Unit, Monasterio Foundation, CNR, Pisa (Italy); Werf, Frans van de; Janssens, Stefan [University Hospitals Leuven, Cardiology Department, Leuven (Belgium)

    2011-04-15

    To describe the time course of myocardial infarct (MI) healing and left ventricular (LV) remodelling and to assess factors predicting LV remodelling using cardiac MRI. In 58 successfully reperfused MI patients, MRI was performed at baseline, 4 months (4M), and 1 year (1Y) post MI Infarct size decreased between baseline and 4M (p < 0.001), but not at 1Y; i.e. 18 {+-} 11%, 12 {+-} 8%, 11 {+-} 6% of LV mass respectively; this was associated with LV mass reduction. Infarct and adjacent wall thinning was found at 4M, whereas significant remote wall thinning was measured at 1Y. LV end-diastolic and end-systolic volumes significantly increased at 1Y, p < 0.05 at 1Y vs. baseline and vs. 4M; this was associated with increased LV sphericity index. No regional or global LV functional improvement was found at follow-up. Baseline infarct size was the strongest predictor of adverse LV remodelling. Infarct healing, with shrinkage of infarcted myocardium and wall thinning, occurs early post-MI as reflected by loss in LV mass and adjacent myocardial remodelling. Longer follow-up demonstrates ongoing remote myocardial and ventricular remodelling. Infarct size at baseline predicts long-term LV remodelling and represents an important parameter for tailoring future post-MI pharmacological therapies designed to prevent heart failure. (orig.)

  13. Early Developmental Assessment of Children with Major Non-Cardiac Congenital Anomalies Predicts Development at the Age of 5 Years

    Science.gov (United States)

    Mazer, Petra; Gischler, Saskia J.; van der Cammen-van Zijp, Monique H. M.; Tibboel, Dick; Bax, Nicolaas M. A.; Ijsselstijn, Hanneke; van Dijk, Monique; Duivenvoorden, Hugo J.

    2010-01-01

    Aim: The aim of this study was to evaluate cognitive and motor development in children with major congenital anomalies and the predictability of development at age 5 years. Method: A prospective, longitudinal follow-up study was undertaken. The Dutch version of the Bayley Scales of Infant Development--Mental Developmental Index (MDI) and…

  14. Computational biomechanics of bone's responses to dental prostheses - osseointegration, remodeling and resorption

    International Nuclear Information System (INIS)

    Clinical and experimental studies showed that human bone has the ability to remodel itself to better adapt to its biomechanical environment by changing both its material properties and geometry. As a consequence of the rapid development and extensive applications of major dental restorations such as implantation and fixed partial denture (FPD), the effect of bone remodeling on the success of a dental restorative surgery is becoming critical for prosthetic design and pre-surgical assessment. This paper aims to provide a computational biomechanics framework to address dental bone's responses as a result of dental restoration. It explored three important issues of resorption, apposition and osseointegration in terms of remodeling simulation. The published remodeling data in long bones were regulated to drive the computational remodeling prediction for the dental bones by correlating the results to clinical data. It is anticipated that the study will provide a more predictive model of dental bone response and help develop a new design methodology for patient-specific dental prosthetic restoration.

  15. Computational biomechanics of bone's responses to dental prostheses - osseointegration, remodeling and resorption

    Science.gov (United States)

    Li, Wei; Rungsiyakull, Chaiy; Field, Clarice; Lin, Daniel; Zhang, Leo; Li, Qing; Swain, Michael

    2010-06-01

    Clinical and experimental studies showed that human bone has the ability to remodel itself to better adapt to its biomechanical environment by changing both its material properties and geometry. As a consequence of the rapid development and extensive applications of major dental restorations such as implantation and fixed partial denture (FPD), the effect of bone remodeling on the success of a dental restorative surgery is becoming critical for prosthetic design and pre-surgical assessment. This paper aims to provide a computational biomechanics framework to address dental bone's responses as a result of dental restoration. It explored three important issues of resorption, apposition and osseointegration in terms of remodeling simulation. The published remodeling data in long bones were regulated to drive the computational remodeling prediction for the dental bones by correlating the results to clinical data. It is anticipated that the study will provide a more predictive model of dental bone response and help develop a new design methodology for patient-specific dental prosthetic restoration.

  16. Stimulating endogenous cardiac regeneration

    Directory of Open Access Journals (Sweden)

    Amanda eFinan

    2015-09-01

    Full Text Available The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration,a combination of these approaches couldameliorate the overall repair process to incorporate the participation ofmultiple cell players.

  17. 视黄酸及相关基因在心脏发育中的作用%The Role of Retinoic Acid and Related Genes in the Cardiac Development

    Institute of Scientific and Technical Information of China (English)

    侯佳; 桂永浩

    2008-01-01

    Retinoic acid,the biologically active form of vitamin A,plays a critical role in normal development.Either an excess or a deficit of retinoic acid produces cardiac defects that vary depending on the severity and the timing of the insult.However,the mechanism of the interaction of retinoic acid and related cardiae genes that leads to cardiac malformation is not elucidated.The review presents retinoic acid's biological character and associated cardiac defects,and then discusses the regulation of retinoic acid and several related genes in the cardiac development.%视黄酸是维生素A在体内重要的生物活性形式,在胚胎和胎儿发育的关键阶段发挥着重要作用.视黄酸水平过高或过低可导致心脏发育异常,但其导致心脏畸形的确切机制尚不明确.本文就视黄酸的生物学特性、视黄酸异常导致的心脏畸形及其与相关心脏转录因子在心脏发育中的作用作一综述.

  18. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis

    NARCIS (Netherlands)

    Gillmore, Julian D.; Maurer, Mathew S.; Falk, Rodney H.; Merlini, Giampaolo; Damy, Thibaud; Dispenzieri, Angela; Wechalekar, Ashutosh D.; Berk, John L.; Quarta, Candida C.; Grogan, Martha; Lachmann, Helen J.; Bokhari, Sabahat; Castano, Adam; Dorbala, Sharmila; Johnson, Geoff B.; Glaudemans, Andor W. J. M.; Rezk, Tamer; Fontana, Marianna; Palladini, Giovanni; Milani, Paolo; Guidalotti, Pierluigi L.; Flatman, Katarina; Lane, Thirusha; Vonberg, Frederick W.; Whelan, Carol J.; Moon, James C.; Ruberg, Frederick L.; Miller, Edward J.; Hutt, David F.; Hazenberg, Bouke P.; Rapezzi, Claudio; Hawkins, Philip N.

    2016-01-01

    Background-Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity of echocardiography and the traditional requirement for histologica

  19. Historical highlights in cardiac pacing.

    Science.gov (United States)

    Geddes, L A

    1990-01-01

    The benchmarks in cardiac pacing are identified, beginning with F. Steiner (1871), who rhythmically stimulated the chloroform-arrested hearts of 3 horses, 1 donkey, 10 dogs, 14 cats, and 8 rabbits. The chloroform-arrested heart in human subjects was paced by T. Greene in the following year (1872) in the UK. In 1882, H. Ziemssen in Germany applied cardiac pacing to a 42-year old woman who had a large defect in the anterior left chest wall subsequent to resection of an enchondroma. Intentional cardiac pacing did not occur until 1932, when A.A. Hyman in the US demonstrated that cardiac pacing could be clinically practical. Hyman made a batteryless pacemaker for delivery in induction shock stimuli (60-120/min) to the atria. His pacemaker was powered by a hand-wound, spring-driven generator which provided 6 min of pacemaking without rewinding. Closed-chest ventricular pacing was introduced in the US in 1952 by P.M. Zoll et al. Zoll (1956) also introduced closed-chest ventricular defibrillation. W.L. Weirich et al. (1958) demonstrated that direct-heart stimulation in closed-chest patients could be achieved with slender wire electrodes. S. Furman and J.B. Schwedel (1959) developed a monopolar catheter electrode for ventricular pacing in man. In the same year, W. Greatbatch and W.M. Chardack developed the implantable pacemaker. PMID:18238328

  20. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy

    DEFF Research Database (Denmark)

    Ito, Hiromu; Koefoed, Mette; Tiyapatanaputi, Prarop;

    2005-01-01

    Structural allograft healing is limited because of a lack of vascularization and remodeling. To study this we developed a mouse model that recapitulates the clinical aspects of live autograft and processed allograft healing. Gene expression analyses showed that there is a substantial decrease in...... the genes encoding RANKL and VEGF during allograft healing. Loss-of-function studies showed that both factors are required for autograft healing. To determine whether addition of these signals could stimulate allograft vascularization and remodeling, we developed a new approach in which rAAV can be...

  1. Endogenous resident c-Kit cardiac stem cells increase in mice with an exercise-induced, physiologically hypertrophied heart

    Directory of Open Access Journals (Sweden)

    Camila Ferreira Leite

    2015-07-01

    Full Text Available Physical activity evokes well-known adaptations in the cardiovascular system. Although exercise training induces cardiac remodeling, whether multipotent stem cells play a functional role in the hypertrophic process remains unknown. To evaluate this possibility, C57BL/6 mice were subjected to swimming training aimed at achieving cardiac hypertrophy, which was morphologically and electrocardiographically characterized. Subsequently, c-Kit+Lin− and Sca-1+Lin− cardiac stem cells (CSCs were quantified using flow cytometry while cardiac muscle-derived stromal cells (CMSCs, also known as cardiac-derived mesenchymal stem cells were assessed using in vitro colony-forming unit fibroblast assay (CFU-F. Only the number of c-Kit+Lin− cells increased in the hypertrophied heart. To investigate a possible extracardiac origin of these cells, a parabiotic eGFP transgenic/wild-type mouse model was used. The parabiotic pairs were subjected to swimming, and the wild-type heart in particular was tested for eGFP+ stem cells. The results revealed a negligible number of extracardiac stem cells in the heart, allowing us to infer a cardiac origin for the increased amount of detected c-Kit+ cells. In conclusion, the number of resident Sca-1+Lin− cells and CMSCs was not changed, whereas the number of c-Kit+Lin− cells was increased during physiological cardiac hypertrophy. These c-Kit+Lin− CSCs may contribute to the physiological cardiac remodeling that result from exercise training.

  2. Remodelling of cellular excitation (reaction) and intercellular coupling (diffusion) by chronic atrial fibrillation represented by a reaction-diffusion system

    Science.gov (United States)

    Zhang, Henggui; Garratt, Clifford J.; Kharche, Sanjay; Holden, Arun V.

    2009-06-01

    Human atrial tissue is an excitable system, in which myocytes are excitable elements, and cell-to-cell electrotonic interactions are via diffusive interactions of cell membrane potentials. We developed a family of excitable system models for human atrium at cellular, tissue and anatomical levels for both normal and chronic atrial fibrillation (AF) conditions. The effects of AF-induced remodelling of cell membrane ionic channels (reaction kinetics) and intercellular gap junctional coupling (diffusion) on atrial excitability, conduction of excitation waves and dynamics of re-entrant excitation waves are quantified. Both ionic channel and gap junctional coupling remodelling have rate dependent effects on atrial propagation. Membrane channel conductance remodelling allows the propagation of activity at higher rates than those sustained in normal tissue or in tissue with gap junctional remodelling alone. Membrane channel conductance remodelling is essential for the propagation of activity at rates higher than 300/min as seen in AF. Spatially heterogeneous gap junction coupling remodelling increased the risk of conduction block, an essential factor for the genesis of re-entry. In 2D and 3D anatomical models, the dynamical behaviours of re-entrant excitation waves are also altered by membrane channel modelling. This study provides insights to understand the pro-arrhythmic effects of AF-induced reaction and diffusion remodelling in atrial tissue.

  3. Cardiac imaging in patients with chronic liver disease

    DEFF Research Database (Denmark)

    Wiese, Signe; Hove, Jens D; Møller, Søren

    2016-01-01

    dysfunction at rest by application of new myocardial strain techniques. Experience with other modalities such as cardiac magnetic resonance imaging and cardiac computed tomography is limited. Future studies exploring these imaging modalities are necessary to characterize and monitor the cardiac changes in...... involved in the development of hepatic nephropathy and is associated with an impaired survival. In the field of cardiac imaging, CCM is not yet a well-characterized entity, hence various modalities of cardiac imaging have been applied. Stress testing with either physiologically or pharmacologically induced...

  4. Ischemic Stroke Due to Cardiac Involvement: Emery Dreifuss Patient

    Directory of Open Access Journals (Sweden)

    Ersin Kasım Ulusoy

    2015-08-01

    Full Text Available Emery-Dreifuss muscular dystrophy (EDMD is a hereditary disease. It is characterized by early-onset contractures, slowly progressive weakness, fatigue related to skapulo-humero-peroneal muscle weakness, cardiomyopathy which develops in adulthood and cardiac conduction system block. Cardiac involvement has a prognostic significance in patients with EDMD and even sudden cardiac death may be the first clinical presentation. In this article, an EDMD patient with ischemic stroke clinic who didn’t have regular cardiac follow-up was reported and the importance of the treatment of cardiac diseases which could play a role in ischemic stroke etiology and the implantation of pace-maker was mentioned.

  5. Hypoxia preconditioned mesenchymal stem cells prevent cardiac fibroblast activation and collagen production via leptin.

    Directory of Open Access Journals (Sweden)

    Panpan Chen

    Full Text Available Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI, due to interstitial fibrosis. Mesenchymal stem cells (MSCs have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC. Leptin has been shown to promote cardiac fibrosis. The expression of leptin is significantly increased in MSCs after HPC but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis.Cardiac fibroblast (CF activation was induced by hypoxia (0.5% O2. The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs, and detecting the expression of α-SMA, SM22α, and collagen IαI in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated using an acute MI model involving permanent ligation of the left anterior descending coronary artery.Co-cultured MSCs decreased fibroblast activation and HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease fibroblast activation. Consistent with this, H-MSCs significantly inhibited cardiac fibrosis after MI and mediated decreased expression of TGF-β/Smad2 and MRTF-A in CFs. These effects were again absent in leptin-deficient MSCs.Our data demonstrate that activation of cardiac fibroblast was inhibited by MSCs in a manner that was leptin-dependent. The mechanism may involve blocking TGF-β/Smad2 and MRTF-A signal pathways.

  6. Preoperative cardiac risk management

    OpenAIRE

    Vidaković Radosav; Poldermans Don; Nešković Aleksandar N.

    2011-01-01

    Approximately 100 million people undergo noncardiac surgery annually worldwide. It is estimated that around 3% of patients undergoing noncardiac surgery experience a major adverse cardiac event. Although cardiac events, like myocardial infarction, are major cause of perioperative morbidity or mortality, its true incidence is difficult to assess. The risk of perioperative cardiac complications depends mainly on two conditions: 1) identified risk factors, and 2) the type of the surgical p...

  7. MRS: a noninvasive window into cardiac metabolism.

    Science.gov (United States)

    van Ewijk, Petronella A; Schrauwen-Hinderling, Vera B; Bekkers, Sebastiaan C A M; Glatz, Jan F C; Wildberger, Joachim E; Kooi, M Eline

    2015-07-01

    A well-functioning heart requires a constant supply of a balanced mixture of nutrients to be used for the production of adequate amounts of adenosine triphosphate, which is the main energy source for most cellular functions. Defects in cardiac energy metabolism are linked to several myocardial disorders. MRS can be used to study in vivo changes in cardiac metabolism noninvasively. MR techniques allow repeated measurements, so that disease progression and the response to treatment or to a lifestyle intervention can be monitored. It has also been shown that MRS can predict clinical heart failure and death. This article focuses on in vivo MRS to assess cardiac metabolism in humans and experimental animals, as experimental animals are often used to investigate the mechanisms underlying the development of metabolic diseases. Various MR techniques, such as cardiac (31) P-MRS, (1) H-MRS, hyperpolarized (13) C-MRS and Dixon MRI, are described. A short overview of current and emerging applications is given. Cardiac MRS is a promising technique for the investigation of the relationship between cardiac metabolism and cardiac disease. However, further optimization of scan time and signal-to-noise ratio is required before broad clinical application. In this respect, the ongoing development of advanced shimming algorithms, radiofrequency pulses, pulse sequences, (multichannel) detection coils, the use of hyperpolarized nuclei and scanning at higher magnetic field strengths offer future perspective for clinical applications of MRS. PMID:26010681

  8. Chronic vagal stimulation for the treatment of low ejection fraction heart failure: results of the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) randomized controlled trial

    OpenAIRE

    Zannad, Faiez; De Ferrari, Gaetano M.; Tuinenburg, Anton E.; Wright, David; Brugada, Josep; Butter, Christian; Klein, Helmut; Stolen, Craig; Meyer, Scott; Stein, Kenneth M.; Ramuzat, Agnes; Schubert, Bernd; Daum, Doug; Neuzil, Petr; Botman, Cornelis

    2014-01-01

    Aim The neural cardiac therapy for heart failure (NECTAR-HF) was a randomized sham-controlled trial designed to evaluate whether a single dose of vagal nerve stimulation (VNS) would attenuate cardiac remodelling, improve cardiac function and increase exercise capacity in symptomatic heart failure patients with severe left ventricular (LV) systolic dysfunction despite guideline recommended medical therapy. Methods: Patients were randomized in a 2 : 1 ratio to receive therapy (VNS ON) or contro...

  9. Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts.

    Science.gov (United States)

    Martin, Tamara P; Lawan, Ahmed; Robinson, Emma; Grieve, David J; Plevin, Robin; Paul, Andrew; Currie, Susan

    2014-02-01

    Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts. PMID:23881186

  10. Eosinophil-Mediated Cholinergic Nerve Remodeling

    OpenAIRE

    Durcan, Niamh; Costello, Richard W; McLean, W. Graham; Blusztajn, Jan; Madziar, Beata; Fenech, Anthony G; Hall, Ian P; Gleich, Gerard J.; McGarvey, Lorcan; Walsh, Marie-Therese

    2006-01-01

    Eosinophils are observed to localize to cholinergic nerves in a variety of inflammatory conditions such as asthma, rhinitis, eosinophilic gastroenteritis, and inflammatory bowel disease, where they are also responsible for the induction of cell signaling.Wehypothesized that a consequence of eosinophil localization to cholinergic nerves would involve a neural remodeling process. Eosinophil co-culture with cholinergic IMR32 cells led to increased expression of the M2 muscar...

  11. PHAGOCYTOSIS AND REMODELING OF COLLAGEN MATRICES

    OpenAIRE

    Abraham, Leah C.; Dice, J. Fred; Lee, Kyongbum; Kaplan, David L.

    2007-01-01

    The biodegradation of collagen and the deposition of new collagen-based extracellular matrices are of central importance in tissue remodeling and function. Similarly, for collagen-based biomaterials used in tissue engineering, the degradation of collagen scaffolds with accompanying cellular infiltration and generation of new extracellular matrix is critical for integration of in vitro grown tissues in vivo. In earlier studies we observed significant impact of collagen structure on primary lun...

  12. Cell wall remodeling under abiotic stress

    OpenAIRE

    Tenhaken, Raimund

    2015-01-01

    Plants exposed to abiotic stress respond to unfavorable conditions on multiple levels. One challenge under drought stress is to reduce shoot growth while maintaining root growth, a process requiring differential cell wall synthesis and remodeling. Key players in this process are the formation of reactive oxygen species (ROS) and peroxidases, which initially cross-link phenolic compounds and glycoproteins of the cell walls causing stiffening. The function of ROS shifts after having converted a...

  13. Application of Petri Nets in Bone Remodeling

    Directory of Open Access Journals (Sweden)

    Lingxi Li

    2009-07-01

    Full Text Available Understanding a mechanism of bone remodeling is a challenging task for both life scientists and model builders, since this highly interactive and nonlinear process can seldom be grasped by simple intuition. A set of ordinary differential equations (ODEs have been built for simulating bone formation as well as bone resorption. Although solving ODEs numerically can provide useful predictions for dynamical behaviors in a continuous time frame, an actual bone remodeling process in living tissues is driven by discrete events of molecular and cellular interactions. Thus, an event-driven tool such as Petri nets (PNs, which may dynamically and graphically mimic individual molecular collisions or cellular interactions, seems to augment the existing ODE-based systems analysis. Here, we applied PNs to expand the ODE-based approach and examined discrete, dynamical behaviors of key regulatory molecules and bone cells. PNs have been used in many engineering areas, but their application to biological systems needs to be explored. Our PN model was based on 8 ODEs that described an osteoprotegerin linked molecular pathway consisting of 4 types of bone cells. The models allowed us to conduct both qualitative and quantitative evaluations and evaluate homeostatic equilibrium states. The results support that application of PN models assists understanding of an event-driven bone remodeling mechanism using PN-specific procedures such as places, transitions, and firings.

  14. Adverse Remodeling of the Electrophysiological Response to Ischemia-Reperfusion in Human Heart Failure Is Associated with Remodeling of Metabolic Gene Expression

    Science.gov (United States)

    Ng, Fu Siong; Holzem, Katherine M.; Koppel, Aaron C.; Janks, Deborah; Gordon, Fabiana; Wit, Andrew L.; Peters, Nicholas S.; Efimov, Igor R.

    2014-01-01

    Background Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion (I-R), although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute I-R in heart failure, and its potential causes, including the remodeling of metabolic gene expression. Methods and Results We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to I-R, with greater action potential duration (APD) shortening (p<0.001 at 8 minutes ischemia; p=0.001 at 12 minutes ischemia) and greater conduction slowing during ischemia, delayed recovery of electrical excitability following reperfusion (F 4.8±1.8 vs. D 1.0±0 mins, p<0.05), and incomplete restoration of APD and conduction velocity early after reperfusion. Expression of 46 metabolic genes were probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%. Conclusions We demonstrate, for the first time in human hearts, that the electrophysiological response to I-R in heart failure is accelerated during ischemia with slower recovery following reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes. PMID:25114062

  15. REMOD: a computational tool for remodeling neuronal dendrites

    Directory of Open Access Journals (Sweden)

    Panagiotis Bozelos

    2014-05-01

    Full Text Available In recent years, several modeling studies have indicated that dendritic morphology is a key determinant of how individual neurons acquire a unique signal processing profile. The highly branched dendritic structure that originates from the cell body, explores the surrounding 3D space in a fractal-like manner, until it reaches a certain amount of complexity. Its shape undergoes significant alterations not only in various neuropathological conditions, but in physiological, too. Yet, despite the profound effect that these alterations can have on neuronal function, the causal relationship between structure and function remains largely elusive. The lack of a systematic approach for remodeling neuronal cells and their dendritic trees is a key limitation that contributes to this problem. In this context, we developed a computational tool that allows the remodeling of any type of neurons, given a set of exemplar morphologies. The tool is written in Python and provides a simple GUI that guides the user through various options to manipulate selected neuronal morphologies. It provides the ability to load one or more morphology files (.swc or .hoc and choose specific dendrites to operate one of the following actions: shrink, remove, extend or branch (as shown in Figure 1. The user retains complete control over the extent of each alteration and if a chosen action is not possible due to pre-existing structural constraints, appropriate warnings are produced. Importantly, the tool can also be used to extract morphology statistics for one or multiple morphologies, including features such as the total dendritic length, path length to the root, branch order, diameter tapering, etc. Finally, an experimental utility enables the user to remodel entire dendritic trees based on preloaded statistics from a database of cell-type specific neuronal morphologies. To our knowledge, this is the first tool that allows (a the remodeling of existing –as opposed to the de novo

  16. Azelnidipine protects myocardium in hyperglycemia-induced cardiac damage

    Directory of Open Access Journals (Sweden)

    Puranik Amrutesh S

    2010-12-01

    Full Text Available Abstract Background Azelnidipine (AZL, a long-acting dihydropyridine-based calcium antagonist, has been recently approved and used for treating ischemic heart disease and cardiac remodeling after myocardial infarction, however, its effect on hyperglycemia-induced cardiac damage has not been studied. Methods This study examined the effect of AZL on circulating markers of cardiac damage, altered lipid and cytokines profile and markers of oxidative stress including homocysteine in diabetic rats. Results STZ induced diabetes caused a significant increase in blood glucose levels. It also resulted in an increase in the levels of homocysteine and cardiac damage markers, like Troponin-1, CK-MB, CK-NAC, uric acid, LDH and alkaline phosphatase. Moreover, there was an increase in the levels of proinflammatory cytokines like TNF-α, IFN-γ, and TGF-β and decrease in the levels of IL-4 and IL-10. Additionally, there was increase in the levels of cholesterol, triglycerides, LDL, VLDL and a decrease in HDL in these animals. There was an altered antioxidant enzyme profile which resulted in a notable increase in the levels of oxidative stress markers like lipid peroxides, nitric oxide and carbonylated proteins. Compared with the untreated diabetic rats, AZL treatment significantly reduced the levels of troponin-1 (P Conclusion Our results indicate that AZL treatment can reduce the risk of hyperglycemia induced metabolic disorders and its role can be further extended to explore its therapeutic potential in diabetic patients with cardiac complications.

  17. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  18. Kinetics of gene expression and bone remodelling in the clinical phase of collagen induced arthritis

    DEFF Research Database (Denmark)

    Denninger, Katja Caroline Marie; Litman, Thomas; Marstrand, Troels;

    2015-01-01

    Introduction: Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of...... clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. Methods: A histological and gene expression profiling time-course study on bone remodelling in CIA was...... declined and remodelling of formed bone dominated. Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and inflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression of genes involved in early and late...

  19. [THE RELATIONSHIP BETWEEN DISORDERS-OF EXTERNAL RESPIRATION AND RIGHT HEART REMODELING IN PATIENTS WITH ATOPIC BRONCHIAL ASTHMA].

    Science.gov (United States)

    Solov'eva, I A; Sobko, E A; Ryazanova, N G; Krapohsina, A Yu; Gorgeeva, N V; Demko, I V

    2015-01-01

    This study aimed at the evaluation of the state of the respiratory system and its possible influence on the structural and functional characteristics of the right heart in patients with atopic bronchial asthma (BA) with a view to optimizing diagnostics and prevention of cardiovascular complications. The study included 189 subjects of whom 148 with BA were divided into 3 groups depending on the severity of the disease. Forty practically healthy volunteers comprised the control group. The external respiration function and right ventricle functional parameters were the main variables measured in all the participants of the study. It was shown that disorders of external respiration and pulmonary hyperinflation progressed with severity of BA and thereby promoted right ventricular myocardium remodeling and dysfunction that in turn led to chronic cardiac insufficiency. It is concluded that functional changes in the right heart in of patients with BA of different severity are associated with remodeling of the respiratory tract. PMID:26964462

  20. Central airways remodeling in COPD patients

    Directory of Open Access Journals (Sweden)

    Pini L

    2014-09-01

    Full Text Available Laura Pini,1 Valentina Pinelli,2 Denise Modina,1 Michela Bezzi,3 Laura Tiberio,4 Claudio Tantucci1 1Unit of Respiratory Medicine, Department of Clinical and Experimental Sciences, University of Brescia, 2Department of Respiratory Medicine, Spedali Civili di Brescia, 3Department Bronchoscopy, Spedali Civili di Brescia, 4Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy Background: The contribution to airflow obstruction by the remodeling of the peripheral airways in chronic obstructive pulmonary disease (COPD patients has been well documented, but less is known about the role played by the large airways. Few studies have investigated the presence of histopathological changes due to remodeling in the large airways of COPD patients. Objectives: The aim of this study was to verify the presence of airway remodeling in the central airways of COPD patients, quantifying the airway smooth muscle (ASM area and the extracellular matrix (ECM protein deposition, both in the subepithelial region and in the ASM, and to verify the possible contribution to airflow obstruction by the above mentioned histopathological changes. Methods: Biopsies of segmental bronchi spurs were performed in COPD patients and control smoker subjects and immunostained for collagen type I, versican, decorin, biglycan, and alpha-smooth muscle actin. ECM protein deposition was measured at both subepithelial, and ASM layers. Results: The staining for collagen I and versican was greater in the subepithelial layer of COPD patients than in control subjects. An inverse correlation was found between collagen I in the subepithelial layer and both forced expiratory volume in 1 second and ratio between forced expiratory volume in 1 second and forced vital capacity. A statistically significant increase of the ASM area was observed in the central airways of COPD patients versus controls. Conclusion: These findings indicate that airway remodeling also affects