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Sample records for cardiovascular adverse remodeling

  1. microRNAs and Cardiovascular Remodeling.

    Science.gov (United States)

    Ono, Koh

    2015-01-01

    Heart failure (HF) is associated with significant morbidity and mortality attributable largely to structural changes in the heart and with associated cardiac dysfunction. Remodeling is defined as alteration of the mass, dimensions, or shape of the heart (termed cardiac or ventricular remodeling) and vessels (vascular remodeling) in response to hemodynamic load and/or cardiovascular injury in association with neurohormonal activation. Remodeling may be described as physiologic or pathologic; alternatively, remodeling may be classified as adaptive or maladaptive. The importance of remodeling as a pathogenic mechanism has been controversial because factors leading to remodeling as well as the remodeling itself may be major determinants of patients' prognosis. The basic mechanisms of cardiovascular remodeling, and especially the roles of microRNAs in HF progression and vascular diseases, will be reviewed here.

  2. Elevated sensitivity to cardiac ischemia in proteinuric rats is independent of adverse cardiac remodeling

    NARCIS (Netherlands)

    Szymanski, Mariusz K.; Hillege, Hans L.; Danser, A. H. Jan; Garrelds, Ingrid M.; Schoemaker, Regien G.

    2013-01-01

    Objectives: Chronic renal dysfunction severely increases cardiovascular risk. Adverse cardiac remodeling is suggested to play a major role as predisposition for increased cardiac ischemic vulnerability. The aim of the present study was to examine the role of adverse cardiac remodeling in cardiac sen

  3. Chromatin remodeling in cardiovascular development and physiology.

    Science.gov (United States)

    Han, Pei; Hang, Calvin T; Yang, Jin; Chang, Ching-Pin

    2011-02-04

    Chromatin regulation provides an important means for controlling cardiac gene expression under different physiological and pathological conditions. Processes that direct the development of normal embryonic hearts and pathology of stressed adult hearts may share general mechanisms that govern cardiac gene expression by chromatin-regulating factors. These common mechanisms may provide a framework for us to investigate the interactions among diverse chromatin remodelers/modifiers and various transcription factors in the fine regulation of gene expression, essential for all aspects of cardiovascular biology. Aberrant cardiac gene expression, triggered by a variety of pathological insults, can cause heart diseases in both animals and humans. The severity of cardiomyopathy and heart failure correlates strongly with abnormal cardiac gene expression. Therefore, controlling cardiac gene expression presents a promising approach to the treatment of human cardiomyopathy. This review focuses on the roles of ATP-dependent chromatin-remodeling factors and chromatin-modifying enzymes in the control of gene expression during cardiovascular development and disease.

  4. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms

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    Yonggang eLiu

    2015-05-01

    Full Text Available EExposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation.

  5. Air pollution and adverse cardiac remodeling: clinical effects and basic mechanisms.

    Science.gov (United States)

    Liu, Yonggang; Goodson, Jamie M; Zhang, Bo; Chin, Michael T

    2015-01-01

    Exposure to air pollution has long been known to trigger cardiovascular events, primarily through activation of local and systemic inflammatory pathways that affect the vasculature. Detrimental effects of air pollution exposure on heart failure and cardiac remodeling have also been described in human populations. Recent studies in both human subjects and animal models have provided insights into the basic physiological, cellular and molecular mechanisms that play a role in adverse cardiac remodeling. This review will give a brief overview of the relationship between air pollution and cardiovascular disease, describe the clinical effects of air pollution exposure on cardiac remodeling, describe the basic mechanisms that affect remodeling as described in human and animal systems and will discuss future areas of investigation.

  6. Straining mode-dependent collagen remodeling in engineered cardiovascular tissue

    NARCIS (Netherlands)

    Rubbens, M.P.; Mol, A.; Marion, M.H. van; Hanemaaijer, R.; Bank, R.A.; Baaijens, F.P.T.; Bouten, C.V.C.

    2009-01-01

    Similar to native cardiovascular tissues, the mechanical properties of engineered cardiovascular constructs depend on the composition and quality of the extracellular matrix, which is a net result of matrix remodeling processes within the tissue. To improve tissue remodeling, and hence tissue mechan

  7. [Cardiovascular pharmacotherapy. Risks and adverse effects].

    Science.gov (United States)

    Voigt, N; Heijman, J; Dobrev, D

    2014-03-01

    Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

  8. Chromatin remodeling in cardiovascular development and physiology

    OpenAIRE

    Han, Pei; Hang, Calvin T.; Yang, Jin; Chang, Ching-Pin

    2011-01-01

    Chromatin regulation provides an important means of controlling cardiac gene expression under different physiological and pathological conditions. Processes that direct the development of normal embryonic hearts and pathology of stressed adult hearts may share general mechanisms that govern cardiac gene expression by chromatin-regulating factors. These common mechanisms may provide a framework for us to investigate the interactions among diverse chromatin remodelers/modifiers and various tran...

  9. Role of mitogen-activated protein kinase pathways in multifactorial adverse cardiac remodeling associated with metabolic syndrome.

    Science.gov (United States)

    Asrih, Mohamed; Mach, François; Nencioni, Alessio; Dallegri, Franco; Quercioli, Alessandra; Montecucco, Fabrizio

    2013-01-01

    Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has been described to result from the cardiac adaptive response to clinical mechanical conditions (such as hypertension, dyslipidemia, and hyperglycemia), soluble inflammatory molecules (such as cytokines and chemokines), as well as hormones (such as insulin), characterizing the pathophysiology of metabolic syndrome. Moreover, these cardiac processes (resulting in cardiac hypertrophy and fibrosis) are also associated with the modulation of intracellular signalling pathways within cardiomyocytes. Amongst the different intracellular kinases, mitogen-activated protein kinases (MAPKs) were shown to be involved in heart damage in metabolic syndrome. However, their role remains controversial. In this paper, we will discuss and update evidence on MAPK-mediated mechanisms underlying cardiac adverse remodeling associated with metabolic syndrome.

  10. Role of Mitogen-Activated Protein Kinase Pathways in Multifactorial Adverse Cardiac Remodeling Associated with Metabolic Syndrome

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    Mohamed Asrih

    2013-01-01

    Full Text Available Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has been described to result from the cardiac adaptive response to clinical mechanical conditions (such as hypertension, dyslipidemia, and hyperglycemia, soluble inflammatory molecules (such as cytokines and chemokines, as well as hormones (such as insulin, characterizing the pathophysiology of metabolic syndrome. Moreover, these cardiac processes (resulting in cardiac hypertrophy and fibrosis are also associated with the modulation of intracellular signalling pathways within cardiomyocytes. Amongst the different intracellular kinases, mitogen-activated protein kinases (MAPKs were shown to be involved in heart damage in metabolic syndrome. However, their role remains controversial. In this paper, we will discuss and update evidence on MAPK-mediated mechanisms underlying cardiac adverse remodeling associated with metabolic syndrome.

  11. Protective Role of the ACE2/Ang-(1–9 Axis in Cardiovascular Remodeling

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    María Paz Ocaranza

    2012-01-01

    Full Text Available Despite reduction in cardiovascular (CV events and end-organ damage with the current pharmacologic strategies, CV disease remains the primary cause of death in the world. Pharmacological therapies based on the renin angiotensin system (RAS blockade are used extensively for the treatment of hypertension, heart failure, and CV remodeling but in spite of their success the prevalence of end-organ damage and residual risk remain still high. Novel approaches must be discovered for a more effective treatment of residual CV remodeling and risk. The ACE2/Ang-(1–9 axis is a new and important target to counterbalance the vasoconstrictive/proliferative RAS axis. Ang-(1–9 is hydrolyzed slower than Ang-(1–7 and is able to bind the Ang II type 2 receptor. We review here the current experimental evidence suggesting that activation of the ACE2/Ang-(1–9 axis protects the heart and vessels (and possibly the kidney from adverse cardiovascular remodeling in hypertension as well as in heart failure.

  12. Liposome-encapsulated berberine treatment reduces adverse ventricle remodeling after myocardial infarction

    NARCIS (Netherlands)

    Wang, J.W.; Allijn, I.E.; Czarny, B.M.S.; Wang, X.Y.; Chong, S.Y.; Pastorin, G.; De Kleijn, D.P.V.; Storm, G.; Schiffelers, R.M.

    2016-01-01

    Introduction: Adverse left ventricle remodeling can be measured as a reduction in ejection fraction after myocardial infarction. Left ventricle remodeling leads to congestive heart failure and is a main determinant of mortality and morbidity after myocardial infarction. Berberine is an isoquinoline

  13. Enhancing cardiac repair : targeting I/R injury and adverse remodeling

    NARCIS (Netherlands)

    Arslan, F.

    2011-01-01

    In this thesis, we have investigated novel therapeutic targets to enhance cardiac repair and improve cardiac function after myocardial infarction. We have tried to approach this objective by targeting 3 major determinants of post-infarct adverse remodeling and subsequent heart function deterioration

  14. ECG marker of adverse electrical remodeling post-myocardial infarction predicts outcomes in MADIT II study.

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    Larisa G Tereshchenko

    Full Text Available BACKGROUND: Post-myocardial infarction (MI structural remodeling is characterized by left ventricular dilatation, fibrosis, and hypertrophy of the non-infarcted myocardium. OBJECTIVE: The goal of our study was to quantify post-MI electrical remodeling by measuring the sum absolute QRST integral (SAI QRST. We hypothesized that adverse electrical remodeling predicts outcomes in MADIT II study participants. METHODS: Baseline orthogonal ECGs of 750 MADIT II study participants (448 [59.7%] ICD arm were analyzed. SAI QRST was measured as the arithmetic sum of absolute QRST integrals over all three orthogonal ECG leads. The primary endpoint was defined as sudden cardiac death (SCD or sustained ventricular tachycardia (VT/ventricular fibrillation (VF with appropriate ICD therapies. All-cause mortality served as a secondary endpoint. RESULTS: Adverse electrical remodeling in post-MI patients was characterized by wide QRS, increased magnitudes of spatial QRS and T vectors, J-point deviation, and QTc prolongation. In multivariable Cox regression analysis after adjustment for age, QRS duration, atrial fibrillation, New York Heart Association heart failure class and blood urea nitrogen, SAI QRST predicted SCD/VT/VF (HR 1.33 per 100 mV*ms (95%CI 1.11-1.59; P = 0.002, and all-cause death (HR 1.27 per 100 mV*ms (95%CI 1.03-1.55, P = 0.022 in both arms. No interaction with therapy arm and bundle branch block (BBB status was found. CONCLUSIONS: In MADIT II patients, increased SAI QRST is associated with increased risk of sustained VT/VF with appropriate ICD therapies and all-cause death in both ICD and in conventional medical therapy arms, and in patients with and without BBB. Further studies of SAI QRST are warranted.

  15. Residual Myocardial Iron Following Intramyocardial Hemorrhage During the Convalescent Phase of Reperfused ST-Segment–Elevation Myocardial Infarction and Adverse Left Ventricular Remodeling

    Science.gov (United States)

    Bulluck, Heerajnarain; Rosmini, Stefania; Abdel-Gadir, Amna; White, Steven K.; Bhuva, Anish N.; Treibel, Thomas A.; Fontana, Marianna; Ramlall, Manish; Hamarneh, Ashraf; Sirker, Alex; Herrey, Anna S.; Manisty, Charlotte; Yellon, Derek M.; Kellman, Peter; Moon, James C.

    2016-01-01

    Background— The presence of intramyocardial hemorrhage (IMH) in ST-segment–elevation myocardial infarction patients reperfused by primary percutaneous coronary intervention has been associated with residual myocardial iron at follow-up, and its impact on adverse left ventricular (LV) remodeling is incompletely understood and is investigated here. Methods and Results— Forty-eight ST-segment–elevation myocardial infarction patients underwent cardiovascular magnetic resonance at 4±2 days post primary percutaneous coronary intervention, of whom 40 had a follow-up scan at 5±2 months. Native T1, T2, and T2* maps were acquired. Eight out of 40 (20%) patients developed adverse LV remodeling. A subset of 28 patients had matching T2* maps, of which 15/28 patients (54%) had IMH. Eighteen of 28 (64%) patients had microvascular obstruction on the acute scan, of whom 15/18 (83%) patients had microvascular obstruction with IMH. On the follow-up scan, 13/15 patients (87%) had evidence of residual iron within the infarct zone. Patients with residual iron had higher T2 in the infarct zone surrounding the residual iron when compared with those without. In patients with adverse LV remodeling, T2 in the infarct zone surrounding the residual iron was also higher than in those without (60 [54–64] ms versus 53 [51–56] ms; P=0.025). Acute myocardial infarct size, extent of microvascular obstruction, and IMH correlated with the change in LV end-diastolic volume (Pearson’s rho of 0.64, 0.59, and 0.66, respectively; P=0.18 and 0.62, respectively, for correlation coefficient comparison) and performed equally well on receiver operating characteristic curve for predicting adverse LV remodeling (area under the curve: 0.99, 0.94, and 0.95, respectively; P=0.19 for receiver operating characteristic curve comparison). Conclusions— The majority of ST-segment–elevation myocardial infarction patients with IMH had residual myocardial iron at follow-up. This was associated with

  16. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

    Energy Technology Data Exchange (ETDEWEB)

    Kali, Avinash; Cokic, Ivan; Tang, Richard; Dohnalkova, Alice; Kovarik, Libor; Yang, Hsin-Jung; Kumar, Andreas; Prato, Frank S.; Wood, John C.; Underhill, David; Marbán, Eduardo; Dharmakumar, Rohan

    2016-11-01

    Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI to characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r

  17. Adverse pregnancy outcomes and cardiovascular risk factor management.

    Science.gov (United States)

    Mehta, Puja K; Minissian, Margo; Bairey Merz, C Noel

    2015-06-01

    Cardiovascular disease (CVD) is the leading health threat to American women. In addition to establish risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman's risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger women often use their obstetrician/gynecologist as their primary health provider, this is an opportune time to diagnose and treat CVD risk factors early. Embedding preventive care providers such as nurse practitioners or physician assistants within OB/GYN practices can be considered, with referral to family medicine or internist for ongoing risk assessment and management. The American Heart Association (AHA)/American Stroke Association (ASA) stroke prevention guidelines tailored to women recommend that women with a history of pre-eclampsia can be evaluated for hypertension and other CVD risk factors within 6 months to 1-year post-partum. Given the burden and impact of CVD on women in our society, the entire medical community must work to establish feasible practice and referral patterns for assessment and treatment of CVD risk factors.

  18. Discontinuation of hormone replacement therapy after myocardial infarction and short term risk of adverse cardiovascular events

    DEFF Research Database (Denmark)

    Bretler, Ditte-Marie; Hansen, Peter Riis; Sørensen, Rikke;

    2012-01-01

    To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue.......To assess the risk of adverse cardiovascular events in women who discontinue hormone replacement therapy after myocardial infarction compared with those who continue....

  19. Impaired autophagy contributes to adverse cardiac remodeling in acute myocardial infarction.

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    Xiaoqian Wu

    Full Text Available OBJECTIVE: Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s, if any, during postinfarction cardiac remodeling. METHODS AND RESULTS: Acute myocardial infarction (AMI was induced by ligating left anterior descending (LAD coronary artery. Autophagy was found to be induced sharply 12-24 hours after surgery by testing LC3 modification and Electron microscopy. P62 degradation in the infarct border zone was increased from day 0.5 to day 3, and however, decreased from day 5 until day 21 after LAD ligation. These results indicated that autophagy was induced in the acute phase of AMI, and however, impaired in the latter phase of AMI. To investigate the significance of the impaired autophagy in the latter phase of AMI, we treated the mice with Rapamycin (an autophagy enhancer, 2.0 mg/kg/day or 3-methyladenine (3MA, an autophagy inhibitor, 15 mg/kg/day one day after LAD ligation until the end of experiment. The results showed that Rapamycin attenuated, while 3MA exacerbated, postinfarction cardiac remodeling and dysfunction respectively. In addition, Rapamycin protected the H9C2 cells against oxygen glucose deprivation in vitro. Specifically, we found that Rapamycin attenuated NFκB activation after LAD ligation. And the inflammatory response in the acute stage of AMI was significantly restrained with Rapamycin treatment. In vitro, inhibition of NFκB restored autophagy in a negative reflex. CONCLUSION: Sustained myocardial ischemia impairs cardiomyocyte autophagy, which is an essential mechanism that protects against adverse cardiac remodeling. Augmenting autophagy could be a therapeutic strategy for acute myocardial infarction.

  20. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1

    DEFF Research Database (Denmark)

    Bai, Bo; Man, Andy W C; Yang, Kangmin;

    2016-01-01

    for the prevention of vascular ageing. Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells. Site...... association of LKB1 with the positive regulatory elements of TGFβ1 promoter. In mice without endothelial nitric oxide synthase, selective overexpression of human SIRT1 in endothelium prevents hypertension and age-related adverse arterial remodeling. Lentiviral-mediated knockdown of HERC2 abolishes...... the beneficial effects of endothelial SIRT1 on both arterial remodeling and arterial blood pressure control. Conclusion-By downregulating acetylated LKB1 protein via HERC2, SIRT1 fine-tunes the crosstalk between endothelial and vascular smooth muscle cells to prevent adverse arterial remodeling and maintain...

  1. No association between anxiety and depression and adverse clinical outcome among patients with cardiovascular disease

    DEFF Research Database (Denmark)

    Kornerup, Henriette; Zwisler, Ann-Dorthe Olsen; Prescott, Eva

    2011-01-01

    Anxiety and depression have been linked to adverse prognostic outcome in patients with cardiovascular disease (CVD) with mixed results. The timing of anxiety and depression measurement has received little attention so far.......Anxiety and depression have been linked to adverse prognostic outcome in patients with cardiovascular disease (CVD) with mixed results. The timing of anxiety and depression measurement has received little attention so far....

  2. ALK7 Gene Polymorphism is Associated with Metabolic Syndrome Risk and Cardiovascular Remodeling

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    Zhang, Wenchao; Wang, Hui; Zhang, Wei [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Lv, Ruijuan [Department of Emergency, Qilu Hospital of Shandong University, Jinan (China); Wang, Zhihao [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Geriatrics, Qilu Hospital of Shandong University, Jinan (China); Shang, Yuanyuan; Zhang, Yun; Zhong, Ming [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Chen, Yuguo; Tang, Mengxiong, E-mail: tangmengxiongsdu8@163.com [Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Jinan (China); Department of Emergency, Qilu Hospital of Shandong University, Jinan (China)

    2013-08-15

    Activin receptor-like kinase 7 (ALK7) is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS) and cardiovascular remodeling in MetS patients. The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05) and was also significantly associated with blood pressure in the total (p < 0.05) and female populations (p < 0.01). Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05). After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs13010956 was also found to be significantly associated with left ventricular mass index in the total (p < 0.05) and female populations (p < 0.05). Our findings suggested that the ALK7 gene polymorphism rs13010956 was significantly associated with MetS risk in females and may be involved in cardiovascular remodeling in MetS patients.

  3. Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: role of autophagy.

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    Zhang, Yao-Jun; Yang, Shao-Hua; Li, Ming-Hui; Iqbal, Javaid; Bourantas, Christos V; Mi, Qiong-Yu; Yu, Yi-Hui; Li, Jing-Jing; Zhao, Shu-Li; Tian, Nai-Liang; Chen, Shao-Liang

    2014-12-01

    The present study aimed to test the hypothesis that berberine, a plant-derived anti-oxidant, attenuates adverse left ventricular remodelling and improves cardiac function in a rat model of myocardial infarction (MI). Furthermore, the potential mechanisms that mediated the cardioprotective actions of berberine, in particular the effect on autophagy, were also investigated. Acute MI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Cardiac function was assessed by transthoracic echocardiography. The protein activity/levels of autophagy related to signalling pathways (e.g. LC-3B, Beclin-1) were measured in myocardial tissue by immunohistochemical staining and western blot. Four weeks after MI, berberine significantly prevented cardiac dysfunction and adverse cardiac remodelling. MI rats treated with low dose berberine (10 mg/kg per day) showed higher left ventricular ejection fraction and fractional shortening than those treated with high-dose berberine (50 mg/kg per day). Both doses reduced interstitial fibrosis and post-MI adverse cardiac remodelling. The cardioprotective action of berberine was associated with increased LC-3B II and Beclin-1 expressions. Furthermore, cardioprotection with berberine was potentially related to p38 MAPK inhibition and phospho-Akt activation. The present in vivo study showed that berberine is effective in promoting autophagy, and subsequently attenuating left ventricular remodelling and cardiac dysfunction after MI. The potential underlying mechanism is augmentation of autophagy through inhibition of p38 MAPK and activation of phospho-Akt signalling pathways.

  4. 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.

  5. Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review

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    Westover Arthur N

    2012-06-01

    Full Text Available Abstract Background There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults. Methods The objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH: ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case–control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable. Results Ten population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association. Conclusions Findings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome

  6. Left ventricular remodeling and hypertrophy in patients with aortic stenosis: insights from cardiovascular magnetic resonance

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    Dweck Marc R

    2012-07-01

    Full Text Available Abstract Background Cardiovascular magnetic resonance (CMR is the gold standard non-invasive method for determining left ventricular (LV mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR. Methods Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening ≥13 mm and >1.5-fold the thickness of the opposing myocardial segment. Results Ninety-one patients (61±21 years; 57 male with aortic stenosis (aortic valve area 0.93±0.32cm2 were recruited. The severity of aortic stenosis was unrelated to the degree (r2=0.012, P=0.43 and pattern (P=0.22 of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02. Six patterns of LV adaption were observed: normal ventricular geometry (n=11, concentric remodeling (n=11, asymmetric remodeling (n=11, concentric hypertrophy (n=34, asymmetric hypertrophy (n=14 and LV decompensation (n=10. Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm with hypertrophic cardiomyopathy. Conclusions We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common. Trial registration ClinicalTrials.gov Reference Number: NCT00930735

  7. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.

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    Viswanathan Rajagopalan

    Full Text Available A large body of evidence suggests that thyroid hormones (THs are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3 treatment in myocardial infarction (MI rats increased left ventricular (LV contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day was available in drinking water ad libitum immediately following MI and continuing for 2 month(s (mo. Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

  8. An update on predictive biomarkers for major adverse cardiovascular events in patients undergoing vascular surgery.

    Science.gov (United States)

    Patelis, Nikolaos; Kouvelos, George N; Koutsoumpelis, Andreas; Moris, Demetrios; Matsagkas, Miltiadis I; Arnaoutoglou, Eleni

    2016-09-01

    Cardiovascular complications signify a major cause of morbidity and mortality in patients undergoing vascular surgery adversely affecting both short- and long-term prognosis. During the last decade, unmet needs for a distinct cardiovascular risk assessment have led to an intensive research for establishment of biomarkers with sufficient predictive value. This literature review aims in examining the value of several biomarkers in predicting the incidence of major adverse cardiac events in vascular surgery patients. We reviewed the English language literature and analyzed the biomarkers as independent predictors or in correlation with other factors. We found several biomarkers showing a significant predictive value for a major adverse cardiovascular event in patients undergoing vascular surgery. These biomarkers can be used in clinical practice as outcome predictors, although sensitivity and specificity varies. Detection of subclinical cardiovascular damage may improve total risk estimation and facilitate clinical assessment of patients at risk for future cardiovascular events. The wide variety of sensitivity and specificity in predicting a MACE of these biomarkers exert the need for future trials in which these markers will be tested as adjunctive tools of cardiovascular risk estimation scoring systems.

  9. Elastin-insufficient mice show normal cardiovascular remodeling in 2K1C hypertension despite higher baseline pressure and unique cardiovascular architecture.

    Science.gov (United States)

    Wagenseil, Jessica E; Knutsen, Russell H; Li, Dean Y; Mecham, Robert P

    2007-07-01

    Mice heterozygous for the elastin gene (ELN(+/-)) show unique cardiovascular properties, including increased blood pressure and smaller, thinner arteries with an increased number of lamellar units. Some of these properties are also observed in humans with supravalvular aortic stenosis, a disease caused by functional heterozygosity of the elastin gene. The arterial geometry in ELN(+/-) mice is contrary to the increased thickness that would be expected in an animal demonstrating hypertensive remodeling. To determine whether this is due to a decreased capability for cardiovascular remodeling or to a novel adaptation of the ELN(+/-) cardiovascular system, we increased blood pressure in adult ELN(+/+) and ELN(+/-) mice using the two-kidney, one-clip Goldblatt model of hypertension. Successfully clipped mice have a systolic pressure increase of at least 15 mmHg over sham-operated animals. ELN(+/+) and ELN(+/-)-clipped mice show significant increases over sham-operated mice in cardiac weight, arterial thickness, and arterial cross-sectional area with no changes in lamellar number. There are no significant differences in most mechanical properties with clipping in either genotype. These results indicate that ELN(+/+) and ELN(+/-) hearts and arteries remodel similarly in response to adult induced hypertension. Therefore, the cardiovascular properties of ELN(+/-) mice are likely due to developmental remodeling in response to altered hemodynamics and reduced elastin levels.

  10. Role of MicroRNAs in Renin-Angiotensin-Aldosterone System-Mediated Cardiovascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari

    2015-01-01

    Full Text Available MicroRNAs are endogenous regulators of gene expression either by inhibiting translation or protein degradation. Recent studies indicate that microRNAs play a role in cardiovascular disease and renin-angiotensin-aldosterone system- (RAAS- mediated cardiovascular inflammation, either as mediators or being targeted by RAAS pharmacological inhibitors. The exact role(s of microRNAs in RAAS-mediated cardiovascular inflammation and remodeling is/are still in early stage of investigation. However, few microRNAs have been shown to play a role in RAAS signaling, particularly miR-155, miR-146a/b, miR-132/122, and miR-483-3p. Identification of specific microRNAs and their targets and elucidating microRNA-regulated mechanisms associated RAS-mediated cardiovascular inflammation and remodeling might lead to the development of novel pharmacological strategies to target RAAS-mediated vascular pathologies. This paper reviews microRNAs role in inflammatory factors mediating cardiovascular inflammation and RAAS genes and the effect of RAAS pharmacological inhibition on microRNAs and the resolution of RAAS-mediated cardiovascular inflammation and remodeling. Also, this paper discusses the advances on microRNAs-based therapeutic approaches that may be important in targeting RAAS signaling.

  11. Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

    Science.gov (United States)

    Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

    2016-01-01

    Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

  12. Effect of Intensive Blood Pressure Control on Cardiovascular Remodeling in Hypertensive Patients with Nephrosclerosis

    Directory of Open Access Journals (Sweden)

    Otelio Randall

    2013-01-01

    Full Text Available Pulse pressure (PP, a marker of arterial system properties, has been linked to cardiovascular (CV complications. We examined (a association between unit changes of PP and (i composite CV outcomes and (ii development of left-ventricular hypertrophy (LVH and (b effect of mean arterial pressure (MAP control on rate of change in PP. We studied 1094 nondiabetics with nephrosclerosis in the African American Study of Kidney Disease and Hypertension. Subjects were randomly assigned to usual MAP goal (102–107 mmHg or a lower MAP goal (≤92 mmHg and randomized to beta-blocker, angiotensin converting enzyme inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11–1.47, P<0.01 and new LVH (RR = 1.26, CI = 1.04–1.54, P=0.02. PP increased at a greater rate in the usual than in lower MAP groups (slope ± SE: 1.08 ± 0.15 versus 0.42 ± 0.15 mmHg/year, P=0.002, but not by the antihypertensive treatment assignment. Observations indicate that control to a lower MAP slows the progression of PP, a correlate of cardiovascular remodeling and complications, and may be beneficial to CV health.

  13. 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.

  14. Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

    Science.gov (United States)

    Zhang, Jie; Fan, Guangpu; Zhao, Hui; Wang, Zhiwei; Li, Fei; Zhang, Peide; Zhang, Jing; Wang, Xu; Wang, Wei

    2017-01-01

    Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated. In this study, we tried to determine the preliminary mechanisms in regulating CF transformation to myofibroblasts and ECM synthesis relevant to the development of adverse cardiac remolding in vivo and in vitro. Our study provides even more evidence that FAK is directly related to the activation of CF in hypoxia condition in a dose-dependent and time-dependent manner. Pharmacological inhibition of FAK significantly reduces myofibroblast differentiation; our in vivo data demonstrated that a FAK inhibitor significantly decreases fibrotic score, and preserves partial left ventricular function. Both PI3K/AKT signalling and ERK1/2 are necessary for hypoxia-induced CF differentiation and ECM synthesis; this process also involves lysyl oxidase (LOX). These findings suggest that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. PMID:28225063

  15. Vagus nerve stimulation mitigates intrinsic cardiac neuronal and adverse myocyte remodeling postmyocardial infarction.

    Science.gov (United States)

    Beaumont, Eric; Southerland, Elizabeth M; Hardwick, Jean C; Wright, Gary L; Ryan, Shannon; Li, Ying; KenKnight, Bruce H; Armour, J Andrew; Ardell, Jeffrey L

    2015-10-01

    This paper aims to determine whether chronic vagus nerve stimulation (VNS) mitigates myocardial infarction (MI)-induced remodeling of the intrinsic cardiac nervous system (ICNS), along with the cardiac tissue it regulates. Guinea pigs underwent VNS implantation on the right cervical vagus. Two weeks later, MI was produced by ligating the ventral descending coronary artery. VNS stimulation started 7 days post-MI (20 Hz, 0.9 ± 0.2 mA, 14 s on, 48 s off; VNS-MI, n = 7) and was compared with time-matched MI animals with sham VNS (MI n = 7) vs. untreated controls (n = 8). Echocardiograms were performed before and at 90 days post-MI. At termination, IC neuronal intracellular voltage recordings were obtained from whole-mount neuronal plexuses. MI increased left ventricular end systolic volume (LVESV) 30% (P = 0.027) and reduced LV ejection fraction (LVEF) 6.5% (P < 0.001) at 90 days post-MI compared with baseline. In the VNS-MI group, LVESV and LVEF did not differ from baseline. IC neurons showed depolarization of resting membrane potentials and increased input resistance in MI compared with VNS-MI and sham controls (P < 0.05). Neuronal excitability and sensitivity to norepinephrine increased in MI and VNS-MI groups compared with controls (P < 0.05). Synaptic efficacy, as determined by evoked responses to stimulating input axons, was reduced in VNS-MI compared with MI or controls (P < 0.05). VNS induced changes in myocytes, consistent with enhanced glycogenolysis, and blunted the MI-induced increase in the proapoptotic Bcl-2-associated X protein (P < 0.05). VNS mitigates MI-induced remodeling of the ICNS, correspondingly preserving ventricular function via both neural and cardiomyocyte-dependent actions.

  16. Injected nanoparticles: the combination of experimental systems to assess cardiovascular adverse effects.

    Science.gov (United States)

    Vlasova, Maria A; Tarasova, Olga S; Riikonen, Joakim; Raula, Janne; Lobach, Anatoly S; Borzykh, Anna A; Smirin, Boris V; Kauppinen, Esko I; Eletskii, Alexander V; Herzig, Karl-Heinz; Salonen, Jarno; Tavi, Pasi; Lehto, Vesa-Pekka; Järvinen, Kristiina

    2014-05-01

    When nanocarriers are used for drug delivery they can often achieve superior therapeutic outcomes over standard drug formulations. However, concerns about their adverse effects are growing due to the association between exposure to certain nanosized particles and cardiovascular events. Here we examine the impact of intravenously injected drug-free nanocarriers on the cardiovasculature at both the systemic and organ levels. We combine in vivo and in vitro methods to enable monitoring of hemodynamic parameters in conscious rats, assessments of the function of the vessels after sub-chronic systemic exposure to nanocarriers and evaluation of the direct effect of nanocarriers on vascular tone. We demonstrate that nanocarriers can decrease blood pressure and increase heart rate in vivo via various mechanisms. Depending on the type, nanocarriers induce the dilation of the resistance arteries and/or change the responses induced by vasoconstrictor or vasodilator drugs. No direct correlation between physicochemical properties and cardiovascular effects of nanoparticles was observed. The proposed combination of methods empowers the studies of cardiovascular adverse effects of the nanocarriers.

  17. Targeting TRAF3IP2 by Genetic and Interventional Approaches Inhibits Ischemia/Reperfusion-induced Myocardial Injury and Adverse Remodeling.

    Science.gov (United States)

    Erikson, John M; Valente, Anthony J; Mummidi, Srinivas; Kandikattu, Hemanth Kumar; DeMarco, Vincent G; Bender, Shawn B; Fay, William P; Siebenlist, Ulrich; Chandrasekar, Bysani

    2017-02-10

    Re-establishing blood supply is the primary goal for reducing myocardial injury in subjects with ischemic heart disease. Paradoxically, reperfusion results in nitroxidative stress and a marked inflammatory response in the heart. TRAF3IP2 (TRAF3 Interacting Protein 2; previously known as CIKS or Act1) is an oxidative stress-responsive cytoplasmic adapter molecule that is an upstream regulator of both IκB kinase (IKK) and c-Jun N-terminal kinase (JNK), and an important mediator of autoimmune and inflammatory responses. Here we investigated the role of TRAF3IP2 in ischemia/reperfusion (I/R)-induced nitroxidative stress, inflammation, myocardial dysfunction, injury, and adverse remodeling. Our data show that I/R up-regulates TRAF3IP2 expression in the heart, and its gene deletion, in a conditional cardiomyocyte-specific manner, significantly attenuates I/R-induced nitroxidative stress, IKK/NF-κB and JNK/AP-1 activation, inflammatory cytokine, chemokine, and adhesion molecule expression, immune cell infiltration, myocardial injury, and contractile dysfunction. Furthermore, Traf3ip2 gene deletion blunts adverse remodeling 12 weeks post-I/R, as evidenced by reduced hypertrophy, fibrosis, and contractile dysfunction. Supporting the genetic approach, an interventional approach using ultrasound-targeted microbubble destruction-mediated delivery of phosphorothioated TRAF3IP2 antisense oligonucleotides into the LV in a clinically relevant time frame significantly inhibits TRAF3IP2 expression and myocardial injury in wild type mice post-I/R. Furthermore, ameliorating myocardial damage by targeting TRAF3IP2 appears to be more effective to inhibiting its downstream signaling intermediates NF-κB and JNK. Therefore, TRAF3IP2 could be a potential therapeutic target in ischemic heart disease.

  18. Association of Selected Antipsychotic Agents With Major Adverse Cardiovascular Events and Noncardiovascular Mortality in Elderly Persons

    DEFF Research Database (Denmark)

    Sahlberg, Marie; Holm, Ellen; Gislason, Gunnar H

    2015-01-01

    events and noncardiovascular mortality associated with individual APs (ziprasidone, olanzapine, risperidone, quetiapine, levomepromazine, chlorprothixen, flupentixol, and haloperidol) in Danish treatment-naïve patients aged ≥70 years. METHODS AND RESULTS: We followed all treatment-naïve Danish citizens...... of treatment, compared with risperidone, incidence rate ratios of major adverse cardiovascular events were higher with use of levomepromazine (3.80, 95% CI 3.43 to 4.21) and haloperidol (1.85, 95% CI 1.67 to 2.05) and lower for treatment with flupentixol (0.54, 95% CI 0.45 to 0.66), ziprasidone (0.31, 95% CI 0...

  19. Association of atherosclerotic renal artery stenosis with major adverse cardiovascular events after acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Zheng Bin; Liu Jinghua; Ma Qin; Zhao Donghui; Wang Xin; Zheng Ze

    2014-01-01

    Background Patients with atherosclerotic renal artery stenosis (ARAS) are in substantial risk of cardiovascular adverse events.We investigated whether myocardial infarction patients with ARAS are in additional risk of cardiovascular events.Methods In this retrospective study,257 patients with type 1 myocardial infarction were enrolled.Median follow-up was 42 months.Composite endpoint events are analyzed by definitions of ARAS as ≥50% or ≥70% diameter stenosis.Results Defining ARAS as ≥70% diameter stenosis,ARAS was a significant predictor for composite endpoint events including death,non-fatal myocardial infarction,ischaemic stroke and intracranial haemorrhage,rehospitalisation for cardiac failure (HR:4.381; 95% Cl:1.770-10.842) by Cox regression analysis,but not for death.Diabetes mellitus was also a significant predictor for composite endpoint events (HR:2.756; 95% Cl:1.295-5.863).However,defining ARAS ≥50% diameter stenosis,ARAS was no longer a significant predictor for composite endpoint events or death.Conclusions Although not associated with mortality,ARAS ≥70% is associated with major adverse cardiac events after acute myocardial infarction.For prognosis,≥70% diameter stenosis is a more appropriate criteria for ARAS definition than ≥50% diameter stenosis.

  20. Adverse Cardiovascular Effects of Nitrous Oxide: It is not all about Hyperhomocysteinaemia

    Directory of Open Access Journals (Sweden)

    Ata Mahmoodpoor

    2015-04-01

    Full Text Available Once admired for its supposed safety, nitrous oxide is presently blamed to increase adverse cardiovascular effects through augmenting plasma homocysteine concentrations (1, 2. Hemodynamic alterations following the administration of nitrous oxide are extremely complicated and sometimes contradictory. Enhanced venous return, arterial pressure, pulmonary and systemic vascular resistance, cardiac output, pupillary dilation and diaphoresis occur under nitrous oxide administration consistent with sympathomimetic properties of nitrous oxide (3. Conversely, reductions in arterial pressure are also probable, especially in patients with coronary artery disease. Nitrous oxide can also depress myocardial contractility due to decreased availability of Ca2+ for contractile activation; yet, myocardial relaxation kinetics remains intact (4. In the presence of a volatile anesthetic, nitrous oxide decreases MVO2 (Myocardial oxygen consumption and myocardial O2 extraction which may exacerbate myocardial ischemia during concomitant reductions in arterial pressure in patients with coronary artery disease. Consequently, it could be conjectured that probable adverse cardiovascular effects following nitrous oxide administration are variable and consequent of a multi-variable phenomenon rather than a single variable such as increased levels of homocysteine. Studied purely focusing on the effects of nitrous oxide are difficult to conduct due to the numerous confounding factors. In a study by Myles et al., hyperhomocysteinemia has been introduced as the source of the adverse cardiovascular effects of nitrous oxide. However, in this study, increased inspired oxygen concentrations were used to overcome arterial desaturation (1. Given the fact that a constant volume and flow rates are used throughout the anesthesia in a particular patient, increasing the concentrations of oxygen would be associated with decreased delivered nitrous oxide and volatile anesthetic concentrations

  1. Paraoxonase 1 polymorphism and prenatal pesticide exposure associated with adverse cardiovascular risk profiles at school age.

    Directory of Open Access Journals (Sweden)

    Helle R Andersen

    Full Text Available BACKGROUND: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1 has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. METHODS: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed. Serum was analyzed for insulin-like growth factor I (IGF-I, insulin-like growth factor binding protein 3 (IGFBP3, insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. RESULTS: Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. CONCLUSION: Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele.

  2. Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

    Science.gov (United States)

    Andersen, Helle R.; Wohlfahrt-Veje, Christine; Dalgård, Christine; Christiansen, Lene; Main, Katharina M.; Nellemann, Christine; Murata, Katsuyuki; Jensen, Tina K.; Skakkebæk, Niels E.; Grandjean, Philippe

    2012-01-01

    Background Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate pesticides. A common polymorphism, PON1 Q192R, affects both properties, but a potential interaction between PON1 genotype and pesticide exposure on cardiovascular risk factors has not been investigated. We explored if the PON1 Q192R genotype affects cardiovascular risk factors in school-age children prenatally exposed to pesticides. Methods Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex specific Z-scores. Results Prenatally pesticide exposed children carrying the PON1 192R-allele had higher abdominal circumference, body fat content, BMI Z-scores, blood pressure, and serum concentrations of leptin and IGF-I at school age than unexposed children. The effects were related to the prenatal exposure level. For children with the PON1 192QQ genotype, none of the variables was affected by prenatal pesticide exposure. Conclusion Our results indicate a gene-environment interaction between prenatal pesticide exposure and the PON1 gene. Only exposed children with the R-allele developed adverse cardiovascular risk profiles thought to be associated with the R-allele. PMID:22615820

  3. Onset of hypertension during pregnancy is associated with long-term worse blood pressure control and adverse cardiac remodeling.

    Science.gov (United States)

    Mesquita, Roberto F; Reis, Muriel; Beppler, Ana Paula; Bellinazzi, Vera Regina; Mattos, Sandra S; Lima-Filho, José L; Cipolli, José A; Coelho-Filho, Otavio R; Pio-Magalhães, José A; Sposito, Andrei C; Matos-Souza, José R; Nadruz, Wilson

    2014-11-01

    Up to 20% of women with hypertensive pregnancy disorders might persist with chronic hypertension. This study compared clinical and echocardiographic features between women whose hypertension began as hypertensive pregnancy disorders (PH group) and women whose diagnosis of hypertension did not occur during pregnancy (NPH group). Fifty PH and 100 NPH women were cross-sectionally evaluated by clinical, laboratory, and echocardiography analysis, and the groups were matched by duration of hypertension. PH exhibited lower age (46.6 ± 1.4 vs. 65.3 ± 1.1 years; P < .001), but higher systolic (159.8 ± 3.9 vs. 148.0 ± 2.5 mm Hg; P = .009) and diastolic (97.1 ± 2.4 vs. 80.9 ± 1.3 mm Hg; P < .001) blood pressure than NPH, although used more antihypertensive classes (3.4 ± 0.2 vs. 2.6 ± 0.1; P < .001). Furthermore, PH showed higher left ventricular wall thickness and increased prevalence of concentric hypertrophy than NPH after adjusting for age and blood pressure. In conclusion, this study showed that PH may exhibit worse blood pressure control and adverse left ventricular remodeling compared with NPH.

  4. CHADS2 Scores in the Prediction of Major Adverse Cardiovascular Events in Patients with Cushing's Syndrome

    Science.gov (United States)

    Chuang, Mei-Hua; Chuang, Tzyy-Ling; Huang, Kung-Yung; Lyu, Shaw-Ruey; Huang, Chih-Yuan; Lee, Ching-Chih

    2014-01-01

    Vascular events are one of the major causes of death in case of Cushing's syndrome (CS). However, due to the relative low frequency of CS, it is hard to perform a risk assessment for these events. As represented congestive heart failure (C), hypertension (H), age (A), diabetes (D), and stroke (S), the CHADS2 score is now accepted to classify the risk of major adverse cardiovascular events (MACEs) in patients with atrial fibrillation. In this study, participants were enrolled from the National Health Research Institute Database (NHIRD) of Taiwan, and we reviewed 551 patients with their sequential clinically diagnosed CS data between 2002 and 2009 in relation to MACEs risk using CHADS2 score. Good correlation could be identified between the CS and CHADS2 score (AUC = 0.795). Our results show that patients with CS show significantly higher risk of vascular events and the CHADS2 score could be applied for MACEs evaluation. Adequate lifestyle modifications and aggressive cardiovascular risks treatment are suggested for CS patients with higher CHADS2 score. PMID:25101124

  5. Fish oil and olive oil supplements attenuate the adverse cardiovascular effects of concentrated ambient air pollution particles exposure in healthy middle-aged adult human volunteers

    Science.gov (United States)

    Exposure to ambient levels of air pollution increases cardiovascular morbidity and mortality. Advanced age is among the factors associated with susceptibility to the adverse effects of air pollution. Dietary fatty acid supplementation has been shown to decrease cardiovascular ris...

  6. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications.

  7. 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

    (CMR) to assess reverse myocardial remodeling in patients after MitraClip implantation. MATERIALS AND METHODS: 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...

  8. Acute and prolonged adverse effects of temperature on mortality from cardiovascular diseases.

    Directory of Open Access Journals (Sweden)

    Yu-Kai Lin

    Full Text Available BACKGROUND: Cardiovascular diseases are the leading causes of death worldwide, especially for developed countries. Elevated mortality from cardiovascular diseases has been shown related to extreme temperature. We thus assessed the risk of mortality from cerebrovascular diseases, heart diseases, and ischemic heart disease (IHD in relation to temperature profiles in four subtropical metropolitans (Taipei, Taichung, Tainan, and Kaohsiung from 1994 to 2007 in Taiwan. METHODS: Distributed lag non-linear models were applied to estimate the cumulative relative risks (RRs with confidence intervals of cause-specific mortality associated with daily temperature from lag 0 to 20 days, and specific effect of extreme temperature episodes with PM10, NOx, and O3, and other potential confounders controlled. Estimates for cause-specific mortalities were then pooled by random-effect meta-analysis. RESULTS: Comparing to centered temperature at 27 °C, the cumulative 4-day (lag 0 to 3 risk of mortality was significantly elevated at 31 °C for cerebrovascular diseases (RR = 1.14; 95% CI: 1.00, 1.31 and heart diseases (RR =  1.22; 95% CI: 1.02, 1.46 , but not for IHD (RR =  1.09; 95% CI: 0.99, 1.21. To the other extreme, at 15 °C, the cumulative 21-day (lag 0 to 20 risk of mortality were also remarkably increased for cerebrovascular diseases, heart diseases, and IHD (RRs  =  1.48 with 95% CI: 1.04, 2.12, 2.04 with 95% CI: 1.61, 2.58, and 1.62 with 95% CI: 1.30, 2.01, respectively. Mortality risks for cardiovascular diseases were generally highest on the present day (lag 0 of extreme heat. No particular finding was detected on prolonged extreme temperature event by pooling estimations for cause-specific mortality. CONCLUSIONS: Low temperature was associated with greater risk of mortality from cardiovascular diseases in comparison with that of high temperature. Adverse effects of extreme temperatures are acute at the beginning of exposure.

  9. Carnitine deprivation adversely affects cardiovascular response to bacterial endotoxin (LPS) in the anesthetized neonatal pig.

    Science.gov (United States)

    Penn, D; Zhang, L; Bobrowski, P J; Quinn, M; Liu, X; McDonough, K H

    1998-11-01

    Sepsis and endotoxemia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine. To investigate whether carnitine deprivation affects the neonate's ability to respond to endotoxin, 19 newborn piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN-) or supplemented (CARN+) with L-carnitine (400 mg/L). Cardiovascular performance, i.e., heart rate; blood pressure (BP); cardiac output (CO); systemic vascular resistance (SVR), and metabolic response, i.e., plasma glucose; lactate; tumor necrosis factor alpha; tissue nitric oxide; and urinary nitrites, were studied serially in anesthetized piglets for 3 h after endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or vehicle administration. Plasma and tissue carnitine values were lower in CARN- than in CARN+ piglets. Prior to LPS, no differences were found for most parameters (excepting lower diastolic BP and SVR in CARN- animals). Systolic, diastolic, and mean BP fell after LPS but recovered by the end of the experiment. Nadirs were lower in CARN- than in CARN+ piglets. CO tended to be higher in CARN- than in CARN+ animals and fell after LPS. SVR fell after LPS and was lower in CARN- than in CARN+ piglets. LPS-treated animals transiently increased urinary flow. By all measures (plasma tumor necrosis factor alpha, glucose and lactate, tissue nitric oxide, and urinary nitrite excretion), LPS provocation was similar for both groups. Chronologically, BP changes were more closely related to SVR than to CO. Our findings suggest that carnitine deprivation diminishes tissue carnitine concentrations and adversely affects cardiovascular response to LPS, in part mediated by the peripheral vasculature.

  10. Influence of age on perioperative major adverse cardiovascular events and mortality risks in elective non-cardiac surgery

    DEFF Research Database (Denmark)

    Hansen, Peter Wæde; Gislason, Gunnar H.; Jørgensen, Mads Emil;

    2016-01-01

    -cause mortality were analyzed by multivariable logistic regression models (adjusted for comorbidities, revised cardiac risk index, cardiovascular pharmacotherapy, body mass index, and surgery type). RESULTS: A total of 386,818 procedures on 302,459 patients were included; mean age was 54.8years (min-max 20......BACKGROUND AND AIMS: Advanced age increases the risk of perioperative cardiovascular complications and may pose reluctance to subject elderly patients to surgery. We examined the impact of high age on perioperative major adverse cardiovascular events (MACE) and mortality in a nationwide cohort...... of patients undergoing elective surgery. METHODS: All Danish patients aged ≥20years undergoing non-cardiac, elective surgery in 2005-2011 were identified from nationwide administrative registers. Risks of 30-day MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, or cardiovascular death) and all...

  11. The role of Notch in the cardiovascular system: potential adverse effects of investigational Notch inhibitors

    Directory of Open Access Journals (Sweden)

    Paola eRizzo

    2015-01-01

    Full Text Available Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta- like ligand 4 (Dll4- activated Notch signalling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long term cardiotoxicity associated to Notch inhibition in cancer patients. In this review we will focus on mechanisms through which inhibition of Notch signalling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor

  12. Concomitant use of clopidogrel and statins and risk of major adverse cardiovascular events following coronary stent implantation

    DEFF Research Database (Denmark)

    Schmidt, Morten; Johansen, Martin B; Mæng, Michael

    2012-01-01

    WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical...... quantification of the interaction effect. WHAT THIS STUDY ADDS • Clopidogrel and CYP3A4-metabolizing statin use were each associated with a substantially reduced rate of major adverse cardiovascular events within 12 months after coronary stent implantation. • Although we observed an interaction between use...... of clopidogrel and statins, statin use vs. non-use was not associated with an increased rate of major adverse cardiovascular events in patients using clopidogrel after coronary stent implantation. AIMS To examine whether CYP3A4-metabolizing statin use modified the association between clopidogrel use and major...

  13. Peri-infarct zone pacing to prevent adverse left ventricular remodelling in patients with large myocardial infarction

    DEFF Research Database (Denmark)

    Stone, Gregg W; Chung, Eugene S; Stancak, Branislav;

    2016-01-01

    AIMS: We sought to determine whether peri-infarct pacing prevents left ventricular (LV) remodelling and improves functional and clinical outcomes in patients with large first myocardial infarction (MI). METHODS AND RESULTS: A total of 126 patients at 27 international sites within 10 days of onset...

  14. Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events

    DEFF Research Database (Denmark)

    Jespersen, Lasse; Hvelplund, Anders; Abildstrøm, Steen Z

    2012-01-01

    AimsPatients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD...... with no obstructive CAD in focus.Methods and resultsWe identified 11 223 patients referred for coronary angiography (CAG) in 1998-2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events.......ConclusionPatients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease....

  15. The role of adverse childhood experiences in cardiovascular disease risk: a review with emphasis on plausible mechanisms.

    Science.gov (United States)

    Su, Shaoyong; Jimenez, Marcia P; Roberts, Cole T F; Loucks, Eric B

    2015-10-01

    Childhood adversity, characterized by abuse, neglect, and household dysfunction, is a problem that exerts a significant impact on individuals, families, and society. Growing evidence suggests that adverse childhood experiences (ACEs) are associated with health decline in adulthood, including cardiovascular disease (CVD). In the current review, we first provide an overview of the association between ACEs and CVD risk, with updates on the latest epidemiological evidence. Second, we briefly review plausible pathways by which ACEs could influence CVD risk, including traditional risk factors and novel mechanisms. Finally, we highlight the potential implications of ACEs in clinical and public health. Information gleaned from this review should help physicians and researchers in better understanding potential long-term consequences of ACEs and considering adapting current strategies in treatment or intervention for patients with ACEs.

  16. The influence of a triclosan toothpaste on adverse events in patients with cardiovascular disease over 5-years.

    Science.gov (United States)

    Cullinan, Mary P; Palmer, Janet E; Carle, Anne D; West, Malcolm J; Westerman, Bill; Seymour, Gregory J

    2015-03-01

    Adverse effects of long-term usage of triclosan-containing toothpaste in humans are currently unknown. We assessed the effect of long-term use of 0.3% triclosan-toothpaste on serious adverse events (SAEs) in patients with cardiovascular disease (CVD). 438 patients with a history of stable CVD were entered into the 5-year longitudinal Cardiovascular and Periodontal Study at Prince Charles Hospital, Brisbane, Australia and randomised into test (triclosan) or placebo groups. There were no significant differences in demographics or clinical features between the groups. Patients were examined at baseline, and annually for 5-years. SAEs were classified according to the System Organ Classes defined by MedDRA (Medical Dictionary for Regulatory Activities). Results were analysed using chi square and Kaplan Meier analysis. Overall, 232 patients (123 in the triclosan group; 109 in the placebo group) experienced 569 SAEs (288 in the triclosan group and 281 in the placebo group). There was no significant difference between the groups in numbers of patients experiencing SAEs (p=0.35) or specific cardiovascular SAEs (p=0.82), nor in time to the first SAE or first cardiovascular SAE, irrespective of gender, age or BMI after adjusting for multiple comparisons (p>0.05). The adjusted odds of experiencing an SAE were estimated to increase by 2.7% for each year of age (p=0.02) and the adjusted odds of experiencing a cardiovascular SAE were estimated to increase by 5.1% for each unit increase in BMI (p=0.02). Most cardiovascular events were related to unstable angina or myocardial infarcts, 21 were associated with arrhythmia and 41 were vascular events such as aortic aneurysm and cerebrovascular accident. Within the limitations of the present study the data suggest that the use of triclosan-toothpaste may not be associated with any increase in SAEs in this CVD population. The long-term impact of triclosan on hormone-related disease, such as cancer, in humans remains to be determined.

  17. Risk of Major Adverse Cardiovascular Events and All-Cause Mortality in Patients With Hidradenitis Suppurativa

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Gislason, Gunnar H; Hansen, Peter R

    2016-01-01

    IMPORTANCE: Hidradenitis suppurativa (HS) is a common inflammatory skin disease. The disease has been associated with cardiovascular (CV) risk factors, but the risk of CV disease in patients with HS is unknown. OBJECTIVE: To investigate CV risk in patients with HS. DESIGN, SETTING, AND PARTICIPAN...

  18. Sustained myocardial production of stromal cell-derived factor-1α was associated with left ventricular adverse remodeling in patients with myocardial infarction.

    Science.gov (United States)

    Uematsu, Manabu; Yoshizaki, Toru; Shimizu, Takuya; Obata, Jun-ei; Nakamura, Takamitsu; Fujioka, Daisuke; Watanabe, Kazuhiro; Watanabe, Yosuke; Kugiyama, Kiyotaka

    2015-11-15

    The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI. An increment in SDF-1α level from AO to AIV, reflecting SDF-1α release from infarcted myocardium, was more frequent in patients with MI in the early phase of MI [n = 52 (65%), P = 0.03] but not in the chronic phase of MI [n = 46 (58%), P = 0.11] compared with that in control patients [n = 6/17 (35%)]. On linear regression analysis, the transmyocardial gradient in SDF-1α level in the chronic phase of MI was correlated with percentage changes in LV end-diastolic volume index (r = 0.39, P infarcted myocardium in the chronic phase of MI was associated with LV adverse remodeling and progressive dysfunction in AMI survivors.

  19. Minimizing Cardiovascular Adverse Effects of Atypical Antipsychotic Drugs in Patients with Schizophrenia

    Directory of Open Access Journals (Sweden)

    Fadi T. Khasawneh

    2014-01-01

    Full Text Available The use of atypical antipsychotic agents has rapidly increased in the United States and worldwide in the last decade. Nonetheless, many health care practitioners do not appreciate the significance of the cardiovascular side effects that may be associated with their use and the means to minimize them. Thus, atypical antipsychotic medications can cause cardiovascular side effects such as arrhythmias and deviations in blood pressure. In rare cases, they may also cause congestive heart failure, myocarditis, and sudden death. Patients with schizophrenia have a higher risk of cardiovascular mortality than healthy individuals, possibly because of excessive smoking, the underlying disorder itself, or a combination of both factors. Increased awareness of these potential complications can allow pharmacists and physicians to better manage and monitor high risk patients. Accurate assessments are very important to avoid medications from being given to patients inappropriately. Additionally, monitoring patients regularly via blood draws and checking blood pressure, heart rate, and electrocardiogram can help catch any clinical problems and prevent further complications. Finally, patient and family-member education, which pharmacists in particular can play key roles in, is central for the management and prevention of side effects, which is known to reflect positively on morbidity and mortality in these patients.

  20. Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis

    Science.gov (United States)

    Wu, Shunquan; Wu, Fuquan; Ding, Yingying; Hou, Jun; Bi, Jingfeng; Zhang, Zheng

    2016-01-01

    Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR = 1.14, 95% CI: 0.99–1.32) and CVD mortality (HR = 1.10, 95% CI: 0.86–1.41). However, NAFLD was associated with an increased risk of prevalent (OR = 1.81, 95% CI: 1.23–2.66) and incident (HR = 1.37, 95% CI: 1.10–1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR = 1.87, 95% CI: 1.47–2.37) and incident (HR = 2.31, 95% CI: 1.46–3.65) coronary artery disease (CAD), prevalent (OR = 1.24, 95% CI: 1.14–1.36) and incident (HR = 1.16, 95% CI: 1.06–1.27) hypertension, and prevalent (OR = 1.32, 95% CI: 1.07–1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD. PMID:27633274

  1. Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance.

    Science.gov (United States)

    Thomas, Liza; Abhayaratna, Walter P

    2017-01-01

    The left atrium is considered a biomarker for adverse cardiovascular outcomes, particularly in patients with left ventricular diastolic dysfunction and atrial fibrillation in whom left atrial (LA) enlargement is of prognostic importance. LA enlargement with a consequent decrease in LA function represents maladaptive structural and functional "remodeling" that in turn promotes electrical remodeling and a milieu conducive for incident atrial fibrillation. Medical and nonmedical interventions may arrest this pathophysiologic process to the extent that subsequent reverse remodeling results in a reduction in LA size and improvement in LA function. This review examines cellular and basic mechanisms involved in LA remodeling, evaluates the noninvasive techniques that can assess these changes, and examines potential mechanisms that may initiate reverse remodeling.

  2. Paraoxonase 1 Polymorphism and Prenatal Pesticide Exposure Associated with Adverse Cardiovascular Risk Profiles at School Age

    DEFF Research Database (Denmark)

    Andersen, Helle R.; Wohlfahrt-Veje, Christine; Dalgard, Christine

    2012-01-01

    Background: Prenatal environmental factors might influence the risk of developing cardiovascular disease later in life. The HDL-associated enzyme paraoxonase 1 (PON1) has anti-oxidative functions that may protect against atherosclerosis. It also hydrolyzes many substrates, including organophosphate...... prenatally exposed to pesticides. Methods: Pregnant greenhouse-workers were categorized as high, medium, or not exposed to pesticides. Their children underwent a standardized examination at age 6-to-11 years, where blood pressure, skin folds, and other anthropometric parameters were measured. PON1-genotype...... was determined for 141 children (88 pesticide exposed and 53 unexposed). Serum was analyzed for insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP3), insulin and leptin. Body fat percentage was calculated from skin fold thicknesses. BMI results were converted to age and sex...

  3. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation

    DEFF Research Database (Denmark)

    Schmidt, M; Johansen, M B; Robertson, D J

    2012-01-01

    Aliment Pharmacol Ther 2012; 35: 165-174 SUMMARY: Background  Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. Aim  To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE...... implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders. Results......  During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0...

  4. Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery

    DEFF Research Database (Denmark)

    Tully, Phillip J; Winefield, Helen R; Baker, Robert A

    2015-01-01

    BACKGROUND: Although depression and anxiety have been implicated in risk for major adverse cardiovascular and cerebrovascular events (MACCE), a theoretical approach to identifying such putative links is lacking. The objective of this study was to examine the association between theoretical...... conceptualisations of depression and anxiety with MACCE at the diagnostic and symptom dimension level. METHODS: Before coronary artery bypass graft (CABG) surgery, patients (N = 158; 20.9 % female) underwent a structured clinical interview to determine caseness for depression and anxiety disorders. Depression...... and anxiety disorders were arranged into the distress cluster (major depression, dysthymia, generalized anxiety disorder, post-traumatic stress disorder) and fear cluster (panic disorder, agoraphobia, social phobia). Patients also completed the self-report Mood and Anxiety Symptom Questionnaire, measuring...

  5. Hormonal regulation of energy-protein homeostasis in hemodialysis patients: an anorexigenic profile that may predispose to adverse cardiovascular outcomes.

    Science.gov (United States)

    Suneja, Manish; Murry, Daryl J; Stokes, John B; Lim, Victoria S

    2011-01-01

    To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with

  6. Adverse effects of androgen deprivation therapy in men with prostate cancer: a focus on metabolic and cardiovascular complications

    Institute of Scientific and Technical Information of China (English)

    Lauren Collins; Shehzad Basaria

    2012-01-01

    Prostate cancer (PCa) is the most common malignancy in men.Prostate being an androgen responsive tissue,androgen deprivation therapy (ADT) is used in the management of locally advanced (improves survival) and metastatic (improves pain and quality of life) PCa.Over the past two decades,the use of ADT has significantly increased as it is also being used in patients with localized disease and those experiencing biochemical recurrences,though without any evidence of survival advantage.Hypogonadism resulting from ADT is associated with decreased muscle mass and strength,increased fat mass,sexual dysfunction,vasomotor symptoms,decreased quality of life,anemia and bone loss.Insulin resistance,diabetes and cardiovascular disease have recently been added to the list of these complications.As the majority of men with PCa die of conditions other than their primary malignancy,recognition and management of these adverse effects is paramount.Here we review data evaluating metabolic and cardiovascular complications of ADT.

  7. CHADS2 Scores in the Prediction of Major Adverse Cardiovascular Events in Patients with Cushing’s Syndrome

    Directory of Open Access Journals (Sweden)

    Yuh-Feng Wang

    2014-01-01

    Full Text Available Vascular events are one of the major causes of death in case of Cushing’s syndrome (CS. However, due to the relative low frequency of CS, it is hard to perform a risk assessment for these events. As represented congestive heart failure (C, hypertension (H, age (A, diabetes (D, and stroke (S, the CHADS2 score is now accepted to classify the risk of major adverse cardiovascular events (MACEs in patients with atrial fibrillation. In this study, participants were enrolled from the National Health Research Institute Database (NHIRD of Taiwan, and we reviewed 551 patients with their sequential clinically diagnosed CS data between 2002 and 2009 in relation to MACEs risk using CHADS2 score. Good correlation could be identified between the CS and CHADS2 score (AUC=0.795. Our results show that patients with CS show significantly higher risk of vascular events and the CHADS2 score could be applied for MACEs evaluation. Adequate lifestyle modifications and aggressive cardiovascular risks treatment are suggested for CS patients with higher CHADS2 score.

  8. Use of clopidogrel and calcium channel blockers and risk of major adverse cardiovascular events

    DEFF Research Database (Denmark)

    Schmidt, Morten; Johansen, Martin B; Robertson, Douglas J

    2012-01-01

    Eur J Clin Invest 2011 ABSTRACT: Background  The CYP3A4 inhibition by calcium channel blockers (CCBs) may attenuate the effectiveness of clopidogrel. Using time-varying drug exposure ascertainment, we examined whether CCB use modified the association between clopidogrel use and major adverse......-month follow-up, we tracked the use of clopidogrel and CCBs and the rate of MACE (composite of myocardial infarction, ischaemic stroke, stent thrombosis, target lesion revascularization, or cardiac death). We used Cox regression to compute hazard ratios, controlling for potential confounders. Results......  Overall, the 12-month risk for MACE was 14·5%. The rate was 130 per 1000 person years for concomitant clopidogrel and CCB use, 106 for clopidogrel without CCB use, 213 for CCB without clopidogrel use, and 248 for no use of either drug. The adjusted hazard ratio for MACE comparing clopidogrel use...

  9. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study

    DEFF Research Database (Denmark)

    Charlot, Mette; Grove, Erik; Hansen, Peter Riis;

    2011-01-01

    OBJECTIVE: To examine the effect of proton pump inhibitors on adverse cardiovascular events in aspirin treated patients with first time myocardial infarction. DESIGN: Retrospective nationwide propensity score matched study based on administrative data. Setting All hospitals in Denmark. PARTICIPANTS...... analysis showed no increase in risk related to use of H(2) receptor blockers (1.04, 0.79 to 1.38; P=0.78). Conclusion In aspirin treated patients with first time myocardial infarction, treatment with proton pump inhibitors was associated with an increased risk of adverse cardiovascular events....

  10. Depression, anxiety and major adverse cardiovascular and cerebrovascular events in patients following coronary artery bypass graft surgery: A five year longitudinal cohort study

    NARCIS (Netherlands)

    P.J. Tully (Phillip); H.R. Winefield (Helen); R.A. Baker (Robert); J. Denollet (Johan); S.S. Pedersen (Susanne); G.A. Wittert (Gary); D.A. Turnbull (Deborah)

    2015-01-01

    textabstractBackground: Although depression and anxiety have been implicated in risk for major adverse cardiovascular and cerebrovascular events (MACCE), a theoretical approach to identifying such putative links is lacking. The objective of this study was to examine the association between theoretic

  11. High intake of dietary tyramine does not deteriorate glucose handling and does not cause adverse cardiovascular effects in mice.

    Science.gov (United States)

    Carpéné, Christian; Schaak, Stéphane; Guilbeau-Frugier, Céline; Mercader, Josep; Mialet-Perez, Jeanne

    2016-09-01

    Tyramine is naturally occurring in food and induces pressor responses. Low-tyramine diets are recommended for patients treated with MAO inhibitors to avoid the fatal hypertensive crisis sadly known as "cheese effect". Hence, tyramine intake is suspected to have toxicological consequences in humans, while its administration to type 1 diabetic rodents has been reported to improve glucose tolerance. We investigated in mice whether prolonged tyramine ingestion could alter glucose homeostasis, insulin sensitivity, adipose tissue physiology or cardiovascular functions. Tyramine was added at 0.04 or 0.14 % in the drinking water since this was estimated to increase by 10- to 40-fold the spontaneous tyramine intake of control mice fed a standard diet. Ten to 12 weeks of such tyramine supplementation did not influence body weight gain, adiposity or food consumption. Both doses (reaching approx. 300 and 1100 μmol tyramine/kg bw/day) decreased nonfasting blood glucose but did not modify glucose tolerance or fasting levels of glucose, insulin or circulating lipids. Blood pressure was not increased in tyramine-drinking mice, while only the higher tested dose moderately increased heart rate without change in its variability. Markers of cardiac tissue injury or oxidative stress remained unaltered, except an increased hydrogen peroxide production in heart preparations. In isolated adipocytes, tyramine inhibited lipolysis similarly in treated and control groups, as did insulin. The lack of serious adverse cardiovascular effects of prolonged tyramine supplementation in normoglycemic mice together with the somewhat insulin-like effects found on adipose cells should lead to reconsider favourably the risk/benefit ratio of the intake of this dietary amine.

  12. t-10, c-12 CLA dietary supplementation inhibits atherosclerotic lesion development despite adverse cardiovascular and hepatic metabolic marker profiles.

    Science.gov (United States)

    Mitchell, Patricia L; Karakach, Tobias K; Currie, Deborah L; McLeod, Roger S

    2012-01-01

    Animal and human studies have indicated that fatty acids such as the conjugated linoleic acids (CLA) found in milk could potentially alter the risk of developing metabolic disorders including diabetes and cardiovascular disease (CVD). Using susceptible rodent models (apoE(-/-) and LDLr(-/-) mice) we investigated the interrelationship between mouse strain, dietary conjugated linoleic acids and metabolic markers of CVD. Despite an adverse metabolic risk profile, atherosclerosis (measured directly by lesion area), was significantly reduced with t-10, c-12 CLA and mixed isomer CLA (Mix) supplementation in both apoE(-/-) (pCLA supplemented animals having distinct patterns, suggestive of hepatic insulin resistance, regardless of mouse strain. The effect of CLA supplementation on hepatic lipid and fatty acid composition was explored in the LDLr(-/-) strain. Dietary supplementation with t-10, c-12 CLA significantly increased liver weight (pCLA also increased the ratio of 18∶1 to 18∶0 fatty acid in the liver suggesting an increase in the activity of stearoyl-CoA desaturase. Changes in plasma adiponectin and liver weight with t-10, c-12 CLA supplementation were evident within 3 weeks of initiation of the diet. These observations provide evidence that the individual CLA isomers have divergent mechanisms of action and that t-10, c-12 CLA rapidly changes plasma and liver markers of metabolic syndrome, despite evidence of reduction in atherosclerosis.

  13. Major Adverse Cardiovascular Events in Treated Periodontitis: A Population-Based Follow-Up Study from Taiwan.

    Directory of Open Access Journals (Sweden)

    Shing-Hsien Chou

    Full Text Available The aim of the present study was to identify the long-term major adverse cardiovascular events (MACE in treated periodontitis patients in Taiwan.From the National Health Insurance Research Database (2001-2010, adult patients (≥ 18 years with treated periodontitis were identified. Comparison was made between patients with mild form and severe form of treated periodontitis after propensity score matching. The primary end point was the incidence of MACE.A total of 32,504 adult patients with treated periodontitis were identified between 2001 and 2010. After propensity score matching, 27,146 patients were preserved for comparison, including 13,573 patients with mild form and 13,573 patients with severe form of treated periodontitis. During follow-up, 728 individuals in mild treated periodontitis group and 1,206 individuals in severe treated periodontitis group had at least 1 MACE event. After adjustment for gender, hyperlipidemia, hypertension and diabetes mellitus, severe treated periodontitis was associated with a mildly but significantly increased risk of MACE among older patients > 60 years of age (incidence rate ratio, 1.26; 95% confidence interval, 1.08-1.46. No association was found among younger patients ≤ 60 years of age.Severe form of treated periodontitis was associated with an increased risk of MACE among older Taiwanese patients, but not among younger Taiwanese patients. We should put more efforts on the improvement of periodontal health to prevent further MACE.

  14. The lysyl oxidase inhibitor (β-aminopropionitrile) reduces leptin profibrotic effects and ameliorates cardiovascular remodeling in diet-induced obesity in rats.

    Science.gov (United States)

    Martínez-Martínez, Ernesto; Rodríguez, Cristina; Galán, María; Miana, María; Jurado-López, Raquel; Bartolomé, María Visitación; Luaces, María; Islas, Fabián; Martínez-González, José; López-Andrés, Natalia; Cachofeiro, Victoria

    2016-03-01

    Lysyl oxidase (LOX) is an extracellular matrix (ECM)-modifying enzyme that has been involved in cardiovascular remodeling. We explore the impact of LOX inhibition in ECM alterations induced by obesity in the cardiovascular system. LOX is overexpressed in the heart and aorta from rats fed a high-fat diet (HFD). β-Aminopropionitrile (BAPN), an inhibitor of LOX activity, significantly attenuated the increase in body weight and cardiac hypertrophy observed in HFD rats. No significant differences were found in cardiac function or blood pressure among any group. However, HFD rats showed cardiac and vascular fibrosis and enhanced levels of superoxide anion (O2(-)), collagen I and transforming growth factor β (TGF-β) in heart and aorta and connective tissue growth factor (CTGF) in aorta, effects that were attenuated by LOX inhibition. Interestingly, BAPN also prevented the increase in circulating leptin levels detected in HFD fed animals. Leptin increased protein levels of collagen I, TGF-β and CTGF, Akt phosphorylation and O2(-) production in both cardiac myofibroblasts and vascular smooth muscle cells in culture, while LOX inhibition ameliorated these alterations. LOX knockdown also attenuated leptin-induced collagen I production in cardiovascular cells. Our findings indicate that LOX inhibition attenuates the fibrosis and the oxidative stress induced by a HFD on the cardiovascular system. The reduction of leptin levels by BAPN in vivo and the ability of this compound to inhibit leptin-induced profibrotic mediators and ROS production in cardiac and vascular cells suggest that interactions between leptin and LOX regulate downstream events responsible for myocardial and vascular fibrosis in obesity.

  15. Analysis of Withdrawn Drugs Because of Cardiovascular Adverse Reactions%因心血管不良反应撤市的药物情况分析

    Institute of Scientific and Technical Information of China (English)

    毛璐; 高杰

    2013-01-01

    OBJECTIVE: To investigate the drugs withdrawn from the market because of cardiovascular adverse reactions in recent years, and to sum up the characteristics leading to cardiovascular adverse reactions and provide reference for rational use of drugs in the clinic. METHODS: Retrieved from domestic and foreign literature databases and the Internet, the data of drugs withdrawn from the market because of cardiovascular adverse reactions and related information were collected and summarized in recent years. RESULTS: In recent years because of cardiovascular events, more than ten drugs were withdrawn, involving non-steroidal anti-inflammatory drugs, diet pills, anti-histamine, etc. CONCLUSION: The cardiovascular adverse drug reactions should be noticed. The dosage and combined use of drugs should be standardized, in order to improve the safety and effectiveness of clinical medication.%目的:调查近年来因心血管不良反应撤市的药品情况,总结其引发心血管不良反应的特点,为临床合理使用药物提供借鉴.方法:检索国内外文献数据库及互联网,收集近年来因引起心血管不良反应而撤市的药物及其相关信息,并进行总结.结果:近年来在国内外因心血管事件撤市的药品涉及非甾体抗炎药、减肥药、抗组胺药等十余品种.结论:临床应警惕药物的心血管不良反应,规范用药剂量及合并药物,提高临床用药的有效性和安全性.

  16. t-10, c-12 CLA dietary supplementation inhibits atherosclerotic lesion development despite adverse cardiovascular and hepatic metabolic marker profiles.

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    Patricia L Mitchell

    Full Text Available Animal and human studies have indicated that fatty acids such as the conjugated linoleic acids (CLA found in milk could potentially alter the risk of developing metabolic disorders including diabetes and cardiovascular disease (CVD. Using susceptible rodent models (apoE(-/- and LDLr(-/- mice we investigated the interrelationship between mouse strain, dietary conjugated linoleic acids and metabolic markers of CVD. Despite an adverse metabolic risk profile, atherosclerosis (measured directly by lesion area, was significantly reduced with t-10, c-12 CLA and mixed isomer CLA (Mix supplementation in both apoE(-/- (p<0.05, n = 11 and LDLr(-/- mice (p<0.01, n = 10. Principal component analysis was utilized to delineate the influence of multiple plasma and tissue metabolites on the development of atherosclerosis. Group clustering by dietary supplementation was evident, with the t-10, c-12 CLA supplemented animals having distinct patterns, suggestive of hepatic insulin resistance, regardless of mouse strain. The effect of CLA supplementation on hepatic lipid and fatty acid composition was explored in the LDLr(-/- strain. Dietary supplementation with t-10, c-12 CLA significantly increased liver weight (p<0.05, n = 10, triglyceride (p<0.01, n = 10 and cholesterol ester content (p<0.01, n = 10. Furthermore, t-10, c-12 CLA also increased the ratio of 18∶1 to 18∶0 fatty acid in the liver suggesting an increase in the activity of stearoyl-CoA desaturase. Changes in plasma adiponectin and liver weight with t-10, c-12 CLA supplementation were evident within 3 weeks of initiation of the diet. These observations provide evidence that the individual CLA isomers have divergent mechanisms of action and that t-10, c-12 CLA rapidly changes plasma and liver markers of metabolic syndrome, despite evidence of reduction in atherosclerosis.

  17. Association of variants in NEDD4L with blood pressure response and adverse cardiovascular outcomes in hypertensive patients treated with thiazide diuretics

    Science.gov (United States)

    McDonough, Caitrin W.; Burbage, Sarah E.; Duarte, Julio D.; Gong, Yan; Langaee, Taimour Y.; Turner, Stephen T.; Gums, John G.; Chapman, Arlene B.; Bailey, Kent R.; Beitelshees, Amber L.; Boerwinkle, Eric; Pepine, Carl J.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.

    2013-01-01

    Objective Single-nucleotide polymorphisms (SNPs) in NEDD4L may influence the ability of the NEDD4L protein to reduce epithelial sodium channel expression. A variant in NEDD4L, rs4149601, was associated with antihypertensive response and cardiovascular outcomes during treatment with thiazide diuretics and β-blockers in a Swedish population. We sought to further evaluate associations between NEDD4L polymorphisms, blood pressure response and cardiovascular outcomes with thiazide diuretics and β-blockers. Methods Four SNPs, rs4149601, rs292449, rs1008899 and rs75982813, were genotyped in 767 patients from the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) clinical trial and association was assessed with blood pressure response to hydrochlorothiazide and atenolol. One SNP, rs4149601, was also genotyped in 1345 patients from the International Verapmil SR Trandolapril Study (INVEST), and association was examined with adverse cardiovascular outcomes relative to hydrochlorothiazide treatment. Results Significant associations or trends were found between rs4149601, rs292449, rs75982813 and rs1008899 and decreases in blood pressure in whites on hydrochlorothiazide, and a significant association was observed with increasing copies of the GC rs4149601-rs292449 haplotype and greater blood pressure response to hydrochlorothiazide in whites (P = 0.0006 and 0.006, SBP and DBP, respectively). Significant associations were also seen with rs4149601 and an increased risk for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide [P = 0.022, odds ratio (95% confidence interval) = 10.65 (1.18–96.25)]. Conclusion NEDD4L rs4149601, rs292449 and rs75982813 may be predictors for blood pressure response to hydrochlorothiazide in whites, and NEDD4L rs4149601 may be a predictor for adverse cardiovascular outcomes in whites not treated with hydrochlorothiazide. PMID:23353631

  18. Association of β-blocker therapy with risks of adverse cardiovascular events and deaths in patients with ischemic heart disease undergoing noncardiac surgery

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Mérie, Charlotte; Jørgensen, Mads

    2014-01-01

    IMPORTANCE: Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction......, ischemic stroke, cardiovascular death, and all-cause death). OBJECTIVE: To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE...... to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy. MAIN OUTCOMES AND MEASURES: Thirty-day risk of MACE and all-cause mortality. RESULTS: Of 28,263 patients with ischemic heart disease undergoing...

  19. LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association

    Directory of Open Access Journals (Sweden)

    Caruppannan Ketheswaram

    2011-04-01

    Full Text Available Abstract Background In patients with severe aortic stenosis (AS, long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability. Hypothesis We hypothesize that changes in LV structure and function following aortic valve replacement (AVR are detectable by CMR and once triggered by AVR, continue for an extended period. Methods Tweny-four patients of which ten (67 ± 12 years, 6 female with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured. Results All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m2, p 2. Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p 2. LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p Conclusion After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.

  20. Hypertension and Cardiovascular Remodelling in Rats Exposed to Continuous Light: Protection by ACE-Inhibition and Melatonin

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    Fedor Simko

    2014-01-01

    Full Text Available Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day or melatonin (10 mg/kg/day. Exposure to continuous light led to hypertension, left ventricular (LV hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.

  1. cardiovasculares

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    Cristina Guerrero

    2006-01-01

    Full Text Available Uno de los aspectos que más discusión ha suscitado en los últimos tiempos entre quienes nos dedicamos al estudio de la emoción tiene que ver con la eventual asociación entre percepción, valoración y respuesta fisiológica. Esto es, siguiendo la máxima aristotélica, cabría cuestionar si las cosas son como son o son como cada quien las percibe. El objetivo de este experimento ha sido establecer la existencia de una conexión entre percepción de control y responsividad cardiovascular. La muestra estudiada ha estado conformada por estudiantes de la Universidad de Castellón; todos ellos han participado de forma voluntaria. La prueba de estrés ha consistido en un examen real de una asignatura troncal de la titulación que cursaban los participantes. Así pues, utilizando una situación de estrés real, hipotetizamos que las respuestas cardiovasculares (medidas a través de la tasa cardiaca, la presión sanguínea sistólica y la presión sanguínea diastólica dependen de la percepción de control que el individuo tiene, o cree tener, sobre la situación.

  2. Validation of the Ability of SYNTAX and Clinical SYNTAX Scores to Predict Adverse Cardiovascular Events After Stent Implantation: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Chen, JiaYuan; Tang, Buzhou; Lin, YongQing; Ru, Ying; Wu, MaoXiong; Wang, Xiaolong; Chen, Qingcai; Chen, YangXin; Wang, JingFeng

    2016-10-01

    To compare the predicative ability of SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) and clinical SYNTAX scores for major adverse cardiac events (MACEs) after stent implantation in patients with coronary artery disease (CAD). Studies were identified by electronic and manual searches. Twenty-six studies were included in the meta-analysis. The pooled C-statistics of SYNTAX score for 1- and 5-year all-cause mortality (ACM) were 0.65 (95% confidence interval [CI]: 0.61-0.68) and 0.62 (95% CI: 0.59-0.65), respectively, with weak heterogeneity. The 1- and 5-year ACM pooled C-statistics for clinical SYNTAX scores were significantly higher at 0.77 and 0.71, respectively (Ps SYNTAX score for predicting 1-year ACM per unit was 1.04 (95% CI: 1.03-1.05). Calibration analysis indicated SYNTAX scores overestimated the risk of major adverse cardiac and cerebrovascular events in each risk stratum. The SYNTAX score demonstrated minimal discrimination in predicting 1- or 5-year adverse cardiovascular events after percutaneous coronary intervention in patients with CAD. The clinical SYNTAX score could further improve the predictive capability for ACM but not MACE.

  3. The Personality and Psychological Stress Predict Major Adverse Cardiovascular Events in Patients With Coronary Heart Disease After Percutaneous Coronary Intervention for Five Years.

    Science.gov (United States)

    Du, Jinling; Zhang, Danyang; Yin, Yue; Zhang, Xiaofei; Li, Jifu; Liu, Dexiang; Pan, Fang; Chen, Wenqiang

    2016-04-01

    To investigate the effects of personality type and psychological stress on the occurrence of major adverse cardiovascular events (MACEs) at 5 years in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Two hundred twenty patients with stable angina (SA) or non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with PCI completed type A behavioral questionnaire, type D personality questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Trait Coping Style Questionnaire (TCSQ), and Symptom Checklist 90 (SCL-90) at 3 days after PCI operation. Meanwhile, biomedical markers (cTnI, CK-MB, LDH, LDH1) were assayed. MACEs were monitored over a 5-year follow-up. NSTE-ACS group had higher ratio of type A behavior, type A/D behavior, and higher single factor scores of type A personality and type D personality than control group and SAP group. NSTE-ACS patients had more anxiety, depression, lower level of mental health (P Type D patients were at a cumulative increased risk of adverse outcome compared with non-type D patients (P type A and type D personality and this tendency was associated with myocardial injury. They also had obvious anxiety, depression emotion, and lower level of mental health, which were related to personality and coping style. Type D personality was an independent predictor of adverse events.

  4. Short- and long-term major cardiovascular adverse events in carotid artery interventions: a nationwide population-based cohort study in Taiwan.

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    Ming-Lung Tsai

    Full Text Available Carotid artery stenosis is one of the leading causes of ischemic stroke. Carotid artery stenting has become well-established as an effective treatment option for carotid artery stenosis. For this study, we aimed to determine the efficacy and safety of carotid stenting in a population-based large cohort of patients by analyzing the Taiwan National Healthcare Insurance (NHI database.2,849 patients who received carotid artery stents in the NHI database from 2004 to 2010 were identified. We analyzed the risk factors of outcomes including major adverse cardiovascular events including death, acute myocardial infarction, and cerebral vascular accidents at 30 days, 1 year, and overall period and further evaluated cause of death after carotid artery stenting.The periprocedural stroke rate was 2.7% and the recurrent stroke rate for the overall follow-up period was 20.3%. Male, diabetes mellitus, and heart failure were significant risk factors for overall recurrent stroke (Hazard Ratio (HR = 1.35, p = 0.006; HR = 1.23, p = 0.014; HR = 1.61, p < 0.001, respectively. The periprocedural acute myocardial infarction rate was 0.3%. Age and Diabetes mellitus were the significant factors to predict periprocedural myocardial infarction (HR = 3.06, p = 0.019; HR = 1.68, p < 0.001, respectively. Periprocedural and overall mortality rates were 1.9% and 17.3%, respectively. The most significant periprocedural mortality risk factor was acute renal failure. Age, diabetes mellitus, acute or chronic renal failure, heart failure, liver disease, and malignancy were factors correlated to the overall period mortality.Periprocedural acute renal failure significantly increased the mortality rate and the number of major adverse cardiovascular events, and the predict power persisted more than one year after the procedure. Age and diabetes mellitus were significant risk factors to predict acute myocardial infarction after carotid artery stenting.

  5. Low health-related quality of life is a predictor of major adverse cardiovascular events in patients with chronic nonischemic heart failure

    Science.gov (United States)

    Zakliczyński, Michał; Owczarek, Aleksander; Partyka, Robert; Mościński, Mateusz; Pudlo, Robert; Kaczmarczyk, Marcin; Zembala, Marian; Poloński, Lech

    2014-01-01

    Introduction The need to indentify patients with chronic heart failure (CHF) at a higher risk of major adverse cardiovascular events (MACEs) has become increasingly important; therefore, new parameters, such as health-related quality of life (HRQoL), are gaining ground. The aim of this study The aim of this study was to determine the risk factors for MACEs, with a special emphasis on HRQoL in chronic non-ischemic heart failure (NIHF) patients. Material and methods This prospective study enrolled 271 hospitalized patients with heart failure symptoms (NYHA II and III), without neoplastic disease, diabetes, hepatic cirrhosis or chronic kidney disease, who had been receiving optimal medical treatment. In all the patients, laboratory examinations, electrocardiography, echocardiography, a 6-minute walking test, invasive right heart pressure measurements and coronary angiography were performed. HRQoL assessment was conducted with the Short-Form Health Survey (SF-36). Clinical observation commenced on admission to the hospital and lasted 3 years. Data concerning MACE incidence (death, transplantation, circulatory support, hospitalization) were obtained during outpatient visits. Results The final analysis enrolled 202 patients, while 17 patients were lost to follow up. The MACE incidence was 42.1%. Major adverse cardiovascular events risk factors in multiple factor analysis were: alkaline phosphatase (hazard ratio [HR] = 1.01; p < 0.05); right ventricular end-diastolic diameter (HR = 1.08; p < 0.001); hsCRP (HR = 1.04; p < 0.05); and the following HRQoL indices: Bodily Pain (HR = 0.98; p < 0.05) and Mental Health (HR = 0.97; p < 0.01). Conclusions Low values for HRQoL parameters (Bodily Pain and Mental Health), right ventricular end-diastolic diameter, serum concentration of hsCRP and alkaline phosphatase are prognostic factors in NIHF patients. PMID:26336436

  6. Body mass index and risk of perioperative cardiovascular adverse events and mortality in 34,744 Danish patients undergoing hip or knee replacement

    DEFF Research Database (Denmark)

    Thornqvist, Catharina; Gislason, Gunnar H; Køber, Lars;

    2014-01-01

    underwent elective primary hip or knee replacement surgery between 2005 and 2011. We used multivariable Cox regression models to calculate the 30-day risks of MACE and mortality associated with 5 BMI groups (underweight (BMI overweight (25-29 kg/m(2)), obese...... 1 (30-34 kg/m(2)), and obese 2 (≥ 35 kg/m(2))). RESULTS: In total, 232 patients (0.7%) had a MACE and 111 (0.3%) died. Compared with overweight, adjusted hazard ratios (HRs) were 1.2 (95% CI: 0.4-3.3), 1.3 (0.95-1.8), 1.6 (1.1-2.2), and 1.0 (0.6-1.9) for underweight, normal weight, obese 1......BACKGROUND AND PURPOSE: Obesity is a risk factor for osteoarthritis in the lower limb, yet the cardiovascular risks associated with obesity in hip or knee replacement surgery are unknown. We examined associations between body mass index (BMI) and the risk of a major adverse cardiovascular event...

  7. A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel.

    Science.gov (United States)

    Thomas, Mark R; Wijeyeratne, Yanushi D; May, Jane A; Johnson, Andrew; Heptinstall, Stan; Fox, Susan C

    2014-01-01

    There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the results of a novel strategy for assessing platelet reactivity (based on P-selectin measurement) are associated with clinical outcomes in patients with acute coronary syndromes (ACS). This was a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel. P-selectin tests designed to assess response to P2Y12 antagonists or aspirin were performed alongside light transmission aggregometry. For the P2Y12 P-selectin test, an optimal cutoff for high platelet reactivity was determined by receiver operating characteristic (ROC) curve analysis. Patients were divided into two cohorts based on this value: patients with (n = 42) or without (n = 58) high platelet reactivity. The primary endpoint was defined as the composite of cardiovascular death, myocardial infarction and stent thrombosis. After 12 months, the primary endpoint occurred in 12 patients. ROC curve analysis determined that the P2Y12 P-selectin test results were predictive of the primary endpoint (area under curve = 0.69, p = 0.046). The primary endpoint occurred more frequently in patients with high on-treatment platelet reactivity compared to those without (21.4% vs. 5.2%; hazard ratio (HR) 4.14; p = 0.026). The P2Y12 P-selectin test results correlated with light transmission aggregometry (Spearman p P-selectin test, only two patients demonstrated high on-treatment platelet reactivity. This study suggests that a P2Y12 P-selectin test is capable of detecting high on-treatment platelet reactivity, which is associated with subsequent cardiovascular events.

  8. Adverse trends of cardiovascular risk factors among low risk populations (1983-1994 - a cohort study of workers and farmers in Guangzhou, China

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    Liu Xiaoqing

    2011-12-01

    Full Text Available Abstract Background The levels and trends of cardiovascular risk factors vary greatly throughout China. We examine 10-year trends of cardiovascular risk factors (1983-1994 and the factors related to these trends among low-risk cohorts of workers and farmers in Guangzhou, China. Methods This is a cohort study of 3,131 workers and 3,493 farmers aged 25-64 years at baseline with 10 years of follow-up. We performed a longitudinal analysis to account for the aging of the cohorts and the repeated measures of the same individual. Results At baseline the prevalence of overweight (including obese ranged from 1.0% to 11.8%, hypertension ranged from 3.8% to 10.5%, and mean serum total cholesterol (TC ranged from 155.4 mg/dl to 187.2 mg/dl. Although prevalence of smoking declined, blood pressure levels and body mass index (BMI increased significantly, and lipid profiles changed unfavorably during the 10-year follow-ups. The prevalence of hypertension increased from 5.0 percentage points (female farmers to 12.3 percentage points (male farmers. Mean TC increased significantly (e.g., +22.8 mg/dl and +17.0 mg/dl in male and female farmers, respectively. In the longitudinal data analyses, increase in BMI was associated with increase in blood pressure levels and TC. Significant adverse trends of risk factors persisted after adjustment for aging, education, BMI, smoking, and alcohol intake. Conclusion Urgent action is needed to prevent and reverse the unhealthy trends occurring among these low risk Chinese workers and farmers.

  9. Role of thyroid hormones in ventricular remodeling.

    Science.gov (United States)

    Rajagopalan, Viswanathan; Gerdes, A Martin

    2015-04-01

    Cardiac remodeling includes alterations in molecular, cellular, and interstitial systems contributing to changes in size, shape, and function of the heart. This may be the result of injury, alterations in hemodynamic load, neurohormonal effects, electrical abnormalities, metabolic changes, etc. Thyroid hormones (THs) serve as master regulators for diverse remodeling processes of the cardiovascular system-from the prenatal period to death. THs promote a beneficial cardiomyocyte shape and improve contractility, relaxation, and survival via reversal of molecular remodeling. THs reduce fibrosis by decreasing interstitial collagen and reduce the incidence and duration of arrhythmias via remodeling ion channel expression and function. THs restore metabolic function and also improve blood flow both by direct effects on the vessel architecture and decreasing atherosclerosis. Optimal levels of THs both in the circulation and in cardiac tissues are critical for normal homeostasis. This review highlights TH-based remodeling and clinically translatable strategies for diverse cardiovascular disorders.

  10. Long-Term Overexpression of Hsp70 Does Not Protect against Cardiac Dysfunction and Adverse Remodeling in a MURC Transgenic Mouse Model with Chronic Heart Failure and Atrial Fibrillation.

    Science.gov (United States)

    Bernardo, Bianca C; Sapra, Geeta; Patterson, Natalie L; Cemerlang, Nelly; Kiriazis, Helen; Ueyama, Tomomi; Febbraio, Mark A; McMullen, Julie R

    2015-01-01

    Previous animal studies had shown that increasing heat shock protein 70 (Hsp70) using a transgenic, gene therapy or pharmacological approach provided cardiac protection in models of acute cardiac stress. Furthermore, clinical studies had reported associations between Hsp70 levels and protection against atrial fibrillation (AF). AF is the most common cardiac arrhythmia presenting in cardiology clinics and is associated with increased rates of heart failure and stroke. Improved therapies for AF and heart failure are urgently required. Despite promising observations in animal studies which targeted Hsp70, we recently reported that increasing Hsp70 was unable to attenuate cardiac dysfunction and pathology in a mouse model which develops heart failure and intermittent AF. Given our somewhat unexpected finding and the extensive literature suggesting Hsp70 provides cardiac protection, it was considered important to assess whether Hsp70 could provide protection in another mouse model of heart failure and AF. The aim of the current study was to determine whether increasing Hsp70 could attenuate adverse cardiac remodeling, cardiac dysfunction and episodes of arrhythmia in a mouse model of heart failure and AF due to overexpression of Muscle-Restricted Coiled-Coil (MURC). Cardiac function and pathology were assessed in mice at approximately 12 months of age. We report here, that chronic overexpression of Hsp70 was unable to provide protection against cardiac dysfunction, conduction abnormalities, fibrosis or characteristic molecular markers of the failing heart. In summary, elevated Hsp70 may provide protection in acute cardiac stress settings, but appears insufficient to protect the heart under chronic cardiac disease conditions.

  11. O polimorfismo do gene AKL7 está associado ao risco de síndrome metabólica e à remodelação cardiovascular ALK7 gene polymorphism is associated with metabolic syndrome risk and cardiovascular remodeling

    Directory of Open Access Journals (Sweden)

    Wenchao Zhang

    2013-01-01

    Full Text Available FUNDAMENTO: Quinase Tipo Receptor de Ativina 7 (ALK7 é um tipo de receptor I para a superfamília TGF-β e recentemente apresentou ter uma função importante na manutenção de homeostase metabólica. OBJETIVO: Investigar a associação do polimorfismo do gene ALK7 à síndrome metabólica (SMet e remodelação cardiovascular em pacientes com SMet. MÉTODOS: O polimorfismo de nucleotídeo único rs13010956 no gene ALK7 foi genotipado em 351 indivíduos chineses submetidos à ultrassonografia cardíaca e das carótidas. As associações do polimorfismo do gene ALK7 ao fenótipo e aos parâmetros da síndrome metabólica e características ultrassônicas cardiovasculares foram analisadas. RESULTADOS: O polimorfismo de rs13010956 no gene ALK7 foi considerado significativamente relacionado ao fenótipo de SMet em mulheres (p BACKGROUND: Activin receptor-like kinase 7 (ALK7 is a type I receptor for the TGF-β superfamily and has recently been demonstrated to play an important role in the maintenance of metabolic homeostasis. OBJECTIVE: To investigate the association of the ALK7 gene polymorphism with metabolic syndrome (MetS and cardiovascular remodeling in MetS patients. METHODS: The single nucleotide polymorphism rs13010956 in the ALK7 gene was genotyped in 351 Chinese subjects undergoing carotid and cardiac ultrasonography. The associations of the ALK7 gene polymorphism with the MetS phenotype, MetS parameters, and cardiovascular ultrasonic features were analyzed. RESULTS: The rs13010956 polymorphism in the ALK7 gene was found to be significantly associated with the MetS phenotype in females (p < 0.05 and was also significantly associated with blood pressure in the total (p < 0.05 and female populations (p < 0.01. Further analysis revealed that rs13010956 was associated with mean intima-media thickness of the carotid arteries in females (p < 0.05. After control for body mass index, blood pressure, fasting blood glucose, and triglycerides, rs

  12. Sex-Specific Associations Between Coronary Artery Plaque Extent and Risk of Major Adverse Cardiovascular Events: from the CONFIRM Long-Term Registry

    Science.gov (United States)

    Gransar, Heidi; Lin, Fay; Valenti, Valentina; Cho, Iksung; Berman, Daniel; Callister, Tracy; DeLago, Augustin; Hadamitzky, Martin; Hausleiter, Joerg; Al-Mallah, Mouaz; Budoff, Matthew; Kaufmann, Philipp; Achenbach, Stephan; Raff, Gilbert; Chinnaiyan, Kavitha; Cademartiri, Filippo; Maffei, Erica; Villines, Todd; Kim, Yong-Jin; Leipsic, Jonathon; Feuchtner, Gudrun; Rubinshtein, Ronen; Pontone, Gianluca; Andreini, Daniele; Marques, Hugo; Shaw, Leslee; Min, James K.

    2016-01-01

    Objective To examine sex-specific associations, if any, between per-vessel CAD extent and the risk of major adverse cardiovascular events (MACE) over a five-year study duration. Background The presence and extent of coronary artery disease (CAD) diagnosed by coronary computed tomography angiography (CCTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of gender on these findings. Methods 5,632 patients (mean age 60.2 + 11.8 years, 36.5% female) from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry were followed over the course of 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional-hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction (MI). Results Obstructive CAD was more prevalent in men (42% vs. 26%, p<0.001) whereas women were more likely to have normal coronary arteries (43% vs. 27%, p<0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and non-obstructive CAD (HR 2.16 for women, 2.56 for men, p<0.001 for both), obstructive one-vessel CAD (HR 3.69 and 2.66, p<0.001), two-vessel CAD (HR 3.92 and 3.55, p<0.001) and three-vessel/left-main CAD (HR 5.94 and 4.44, p<0.001). Further exploratory analyses of atherosclerotic burden did not identify gender-specific patterns predictive of MACE. Conclusion In a large prospective CCTA cohort followed long-term, we did not observe an interaction of gender for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by CCTA for the risk of MACE in both women and men. PMID:27056154

  13. Monitoring and analysis of adverse reactions associated with medicines recently approved for treatment of cardiovascular disease collected through the spontaneous reporting system

    OpenAIRE

    Tarapués Román, Mónica Natalie

    2015-01-01

    Existen varios medicamentos disponibles para el tratamiento de la patología cardiovascular, así como para otras enfermedades consideradas factores de riesgo cardiovasculares, como son; diabetes, hipertensión y dislipidemia. Cuando un medicamento es comercializado por primera vez, su perfil de seguridad debe considerarse provisional debido a limitaciones propias de los ensayos clínicos pre-comercialización. Para los nuevos medicamentos, la información relevante sobre su seguridad en la poblaci...

  14. Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study

    DEFF Research Database (Denmark)

    Friis-Møller, Nina; Thiébaut, Rodolphe; Reiss, Peter;

    2010-01-01

    aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. METHODS AND RESULTS: Prospective multinational cohort study. The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection.......670-0.818) for coronary heart disease and 0.769 (0.695-0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. CONCLUSION: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters...

  15. Relation of Serum Adiponectin Levels to Number of Traditional Atherosclerotic Risk Factors and All-Cause Mortality and Major Adverse Cardiovascular Events (from the Copenhagen City Heart Study)

    DEFF Research Database (Denmark)

    Lindberg, Soren; Mogelvang, Rasmus; Pedersen, Sune H;

    2013-01-01

    Adiponectin exerts anti-inflammatory and antiatherogenic effects and appears to protect against arteriosclerosis. Accordingly, an association between low concentrations of plasma adiponectin and cardiovascular (CV) disease has been demonstrated in several studies. In contrast, elevated plasma...... or nonfatal myocardial infarction or ischemic stroke (n = 502). High adiponectin was inversely associated with an increasing number of traditional CV risk factors (p...

  16. Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population

    Science.gov (United States)

    Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T)...

  17. Evaluation of risk profiles for gastrointestinal and cardiovascular adverse effects in nonselective NSAID and COX-2 inhibitor users - A cohort study using pharmacy dispensing data in the Netherlands

    NARCIS (Netherlands)

    Layton, Deborah; Souverein, Patrick C.; Heerdink, Eibert R.; Shakir, Saad A. W.; Egberts, Antoine C. G.

    2008-01-01

    Background: Newly approved drugs, in comparison with older drugs, are more often prescribed to patients who have not responded satisfactorily to established related drugs or as first-line therapy to patients with a high baseline risk for adverse outcomes (i.e. channelling). However, these patients a

  18. Cardiovascular pharmacogenetics.

    Science.gov (United States)

    Myburgh, Renier; Hochfeld, Warren E; Dodgen, Tyren M; Ker, James; Pepper, Michael S

    2012-03-01

    Human genetic variation in the form of single nucleotide polymorphisms as well as more complex structural variations such as insertions, deletions and copy number variants, is partially responsible for the clinical variation seen in response to pharmacotherapeutic drugs. This affects the likelihood of experiencing adverse drug reactions and also of achieving therapeutic success. In this paper, we review key studies in cardiovascular pharmacogenetics that reveal genetic variations underlying the outcomes of drug treatment in cardiovascular disease. Examples of genetic associations with drug efficacy and toxicity are described, including the roles of genetic variability in pharmacokinetics (e.g. drug metabolizing enzymes) and pharmacodynamics (e.g. drug targets). These findings have functional implications that could lead to the development of genetic tests aimed at minimizing drug toxicity and optimizing drug efficacy in cardiovascular medicine.

  19. Radiation-induced cardiovascular effects

    Science.gov (United States)

    Tapio, Soile

    Recent epidemiological studies indicate that exposure to ionising radiation enhances the risk of cardiovascular mortality and morbidity in a moderate but significant manner. Our goal is to identify molecular mechanisms involved in the pathogenesis of radiation-induced cardiovascular disease using cellular and mouse models. Two radiation targets are studied in detail: the vascular endothelium that plays a pivotal role in the regulation of cardiac function, and the myocardium, in particular damage to the cardiac mitochondria. Ionising radiation causes immediate and persistent alterations in several biological pathways in the endothelium in a dose- and dose-rate dependent manner. High acute and cumulative doses result in rapid, non-transient remodelling of the endothelial cytoskeleton, as well as increased lipid peroxidation and protein oxidation of the heart tissue, independent of whether exposure is local or total body. Proteomic and functional changes are observed in lipid metabolism, glycolysis, mitochondrial function (respiration, ROS production etc.), oxidative stress, cellular adhesion, and cellular structure. The transcriptional regulators Akt and PPAR alpha seem to play a central role in the radiation-response of the endothelium and myocardium, respectively. We have recently started co-operation with GSI in Darmstadt to study the effect of heavy ions on the endothelium. Our research will facilitate the identification of biomarkers associated with adverse cardiac effects of ionising radiation and may lead to the development of countermeasures against radiation-induced cardiac damage.

  20. Being born under adverse economic conditions leads to a higher cardiovascular mortality rate later in life: evidence based on individuals born at different stages of the business cycle

    DEFF Research Database (Denmark)

    van den Berg, Gerard J; Doblhammer-Reiter, Gabriele; Christensen, Kaare

    2011-01-01

    since the 1870s and including the cause of death. To capture exogenous variation of conditions early in life, we use the state of the business cycle around birth. We find significant negative effects of economic conditions around birth on the individual CV mortality rate at higher ages......We connect the recent medical and economic literatures on the long-run effects of early-life conditions by analyzing the effects of economic conditions on the individual cardiovascular (CV) mortality rate later in life, using individual data records from the Danish Twin Registry covering births....... There is no effect on the cancer-specific mortality rate. From variation within and between monozygotic and dizygotic twin pairs born under different conditions, we conclude that the fate of an individual is more strongly determined by genetic and household-environmental factors if early-life conditions are poor...

  1. 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

  2. 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

    2016-06-22

    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.

  3. ADMA, cardiovascular disease and diabetes.

    Science.gov (United States)

    Krzyzanowska, Katarzyna; Mittermayer, Friedrich; Wolzt, Michael; Schernthaner, Guntram

    2008-12-15

    The endogenous competitive nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an emerging risk marker for future cardiovascular events. Elevated ADMA concentrations have been described in patients with an adverse cardiovascular risk profile. Recently, various studies investigated the independent role of ADMA as a cardiovascular risk predictor in several patient cohorts. In addition, ADMA might not only be a risk marker but also a causative factor for cardiovascular disease. This review summarizes the literature on the relationship between ADMA, cardiovascular disease and diabetes.

  4. Immune modulation of resistance artery remodelling.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2012-01-01

    Low-grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune responses participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodelling that occurs in cardiovascular disease. Effector T cells such as T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (that produce interleukin-4), as well as Th17 (that produce interleukin-17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone-salt and aldosterone-salt, as well as in models of hypertension such as the Dahl-salt-sensitive rat. The mechanism whereby the immune system is activated is unclear, but it has been suggested that neo-antigens may be generated by the elevation of blood pressure or other stimuli, leading to the activation of the immune response. Activated Th1 may contribute to vascular remodelling directly on blood vessels via effects of the cytokines produced or indirectly by actions on the kidney. The protective effect of Treg may be mediated similarly directly or via renal effects. These data offer promise for the discovery of new therapeutic targets to ameliorate vascular remodelling, which could lead to improved outcome in cardiovascular disease in humans.

  5. Risk of cardiovascular adverse events from trastuzumab (Herceptin(®)) in elderly persons with breast cancer: a population-based study.

    Science.gov (United States)

    Tsai, H-T; Isaacs, C; Fu, A Z; Warren, J L; Freedman, A N; Barac, A; Huang, C-Y; Potosky, A L

    2014-02-01

    Randomized controlled trials have reported a 4-5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin (®) ) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77-2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66-75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006-2007 vs. 1.86 for 1998-2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients' diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.

  6. Fructose Containing Sugars at Normal Levels of Consumption Do Not Effect Adversely Components of the Metabolic Syndrome and Risk Factors for Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Theodore J. Angelopoulos

    2016-03-01

    Full Text Available The objective of the current study was to explore our hypothesis that average consumption of fructose and fructose containing sugars would not increase risk factors for cardiovascular disease (CVD and the metabolic syndrome (MetS. A randomized, double blind, parallel group study was conducted where 267 individuals with BMI between 23 and 35 kg/m2 consumed low fat sugar sweetened milk, daily for ten weeks as part of usual weight-maintenance diet. One group consumed 18% of calories from high fructose corn syrup (HFCS, another group consumed 18% of calories from sucrose, a third group consumed 9% of calories from fructose, and the fourth group consumed 9% of calories from glucose. There was a small change in waist circumference (80.9 ± 9.5 vs. 81.5 ± 9.5 cm in the entire cohort, as well as in total cholesterol (4.6 ± 1.0 vs. 4.7 ± 1.0 mmol/L, p < 0.01, triglycerides (TGs (11.5 ± 6.4 vs. 12.6 ± 8.9 mmol/L, p < 0.01, and systolic (109.2 ± 10.2 vs. 106.1 ± 10.4 mmHg, p < 0.01 and diastolic blood pressure (69.8 ± 8.7 vs. 68.1 ± 9.7 mmHg, p < 0.01. The effects of commonly consumed sugars on components of the MetS and CVD risk factors are minimal, mixed and not clinically significant.

  7. Fructose Containing Sugars at Normal Levels of Consumption Do Not Effect Adversely Components of the Metabolic Syndrome and Risk Factors for Cardiovascular Disease

    Science.gov (United States)

    Angelopoulos, Theodore J.; Lowndes, Joshua; Sinnett, Stephanie; Rippe, James M.

    2016-01-01

    The objective of the current study was to explore our hypothesis that average consumption of fructose and fructose containing sugars would not increase risk factors for cardiovascular disease (CVD) and the metabolic syndrome (MetS). A randomized, double blind, parallel group study was conducted where 267 individuals with BMI between 23 and 35 kg/m2 consumed low fat sugar sweetened milk, daily for ten weeks as part of usual weight-maintenance diet. One group consumed 18% of calories from high fructose corn syrup (HFCS), another group consumed 18% of calories from sucrose, a third group consumed 9% of calories from fructose, and the fourth group consumed 9% of calories from glucose. There was a small change in waist circumference (80.9 ± 9.5 vs. 81.5 ± 9.5 cm) in the entire cohort, as well as in total cholesterol (4.6 ± 1.0 vs. 4.7 ± 1.0 mmol/L, p < 0.01), triglycerides (TGs) (11.5 ± 6.4 vs. 12.6 ± 8.9 mmol/L, p < 0.01), and systolic (109.2 ± 10.2 vs. 106.1 ± 10.4 mmHg, p < 0.01) and diastolic blood pressure (69.8 ± 8.7 vs. 68.1 ± 9.7 mmHg, p < 0.01). The effects of commonly consumed sugars on components of the MetS and CVD risk factors are minimal, mixed and not clinically significant. PMID:27023594

  8. 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.

  9. 戒烟药物的心血管不良反应%Cardiovascular adverse reaction of pharmacologic agents for cessation

    Institute of Scientific and Technical Information of China (English)

    丁荣晶

    2013-01-01

    Smoking cessation can reduce morbidity and mortality of cardiovascular disease(CVD), which is important in CVD secondary prevention. Smoking is a chronic addiction disease, smoking cessation lead to relapse, often due to withdrawal symptoms. Psychological support and pharmacologic agents for cessation are needed during the smoking cessation process. Multiple randomized, control ed clinical trials demonstrated the benefits of counseling patients with CVD on smoking cessation. In contrast, relatively few clinical trials tested the safety or efficacy of pharmacotherapy for smokers with CVD. Researchers raised concerns about the safety of NRT, champix and sustained-release bupropion in patients with CVD, because both agents can have sympathetic activity and can theoretical y increase myocardial work, and NRT might also aggravate endothelial dysfunction, and reduce the myocardial oxygen supply through coronary vasoconstriction .So more and more doctors has paid attention on the safety of pharmacotherapy in smokers with CVD.%  戒烟可降低心血管疾病发生和死亡风险,是心血管疾病二级预防的重要内容。吸烟是一种慢性成瘾性疾病,戒烟过程中常因戒断症状导致复吸,在戒烟过程中需要心理支持治疗和戒烟药物辅助治疗。许多随机对照临床试验证实,戒烟心理辅导有助于患有心血管疾病吸烟者的戒烟。但很少有临床试验证实戒烟药物在心血管疾病患者应用的安全性及有效性。由于尼古丁替代治疗,以及缓释安非他酮和伐尼克兰均可引起交感神经兴奋,理论上增加心肌作功,提高心肌耗氧量;其中尼古丁替代治疗还可能引起内皮功能障碍,使冠状动脉收缩,心肌供氧量减少,因此,越来越多的研究者开始关注合并心血管疾病吸烟者中戒烟药物应用的安全性。

  10. Predictors and prognostic value of left atrial remodelling after acute myocardial infarction

    DEFF Research Database (Denmark)

    Kyhl, Kasper; Vejlstrup, Niels; Lønborg, Jacob;

    2015-01-01

    PURPOSE: Left atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling...... remodelling. Kaplan-Meier and Log Rank analyses showed that patients in the highest tertiles of LAmin or LAmax remodelling are at higher risk (0.030 and p=0.018). CONCLUSIONS: After a myocardial infarction, LA remodelling reflects a parallel ventricular-atrial remodelling. Infarct size is a major determinant......, larger infarct size by CMR, higher peak troponin T, larger area at risk and adverse left ventricular (LV) remodelling. LA maximum volume (LAmax) remodelling was correlated to larger infarct size by CMR, higher peak troponin T, larger area at risk, larger LV mass, impaired LV function and adverse LV...

  11. Infusão intravenosa de vasopressina causa efeitos cardiovasculares adversos dose-dependentes em cães anestesiados Infusión intravenosa de vasopresina causa efectos cardiovasculares adversos dependientes de la dosis en canes anestesiados Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs

    Directory of Open Access Journals (Sweden)

    Luiz Cláudio Martins

    2010-02-01

    hemodinámico en la práctica clínica, especialmente cuando son necesarias dosis mayores a 0,01 U/kg/min.BACKGROUND: Arginine vasopressin (AVP has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8 and AVP (n=8 groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min, at them 20-min intervals. Heart rate (HR and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min a progressive increase in mean arterial pressure (MAP and systemic vascular resistance index (SVRI were observed, with a significant decrease in HR and the cardiac index (CI. A significant increase in the pulmonary vascular resistance index (PVRI was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed.

  12. A meta-analysis on the efficacy of stem cell transplantation therapy on the prevention of cardiac remodeling and main adverse cardiovascular event in patients with chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    何炜

    2013-01-01

    Objective Stem cell transplantation is a promising strategy in cardiology.This meta-analysis summarizes the efficacy and safety of stem cells transplantation on top of standard medication on chronic heart failure patients

  13. Exercise-induced cardiac remodeling.

    Science.gov (United States)

    Weiner, Rory B; Baggish, Aaron L

    2012-01-01

    Early investigations in the late 1890s and early 1900s documented cardiac enlargement in athletes with above-normal exercise capacity and no evidence of cardiovascular disease. Such findings have been reported for more than a century and continue to intrigue scientists and clinicians. It is well recognized that repetitive participation in vigorous physical exercise results in significant changes in myocardial structure and function. This process, termed exercise-induced cardiac remodeling (EICR), is characterized by structural cardiac changes including left ventricular hypertrophy with sport-specific geometry (eccentric vs concentric). Associated alterations in both systolic and diastolic functions are emerging as recognized components of EICR. The increasing popularity of recreational exercise and competitive athletics has led to a growing number of individuals exhibiting these findings in routine clinical practice. This review will provide an overview of EICR in athletes.

  14. 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...

  15. Analysis of Association between Adverse Drug Reactions Induced by Cardiovascular and Cerebrovascular Drugs and Patients%心脑血管用药不良反应与用药人群间的关联关系分析

    Institute of Scientific and Technical Information of China (English)

    冯变玲; 魏芬; 杨世民; 赵君; 雷祎; 覃蓝

    2011-01-01

    目的 分析药品不良反应与用药人群的性别、年龄间潜在的关联关系,为心脑血管类疾病用药的安全、合理、有效提供参考.方法 根据江苏省药品不良反应监测中心2004-2009年收集的9 640份心脑血管疾病用药不良反应报告数据,运用数据挖掘技术中广义规则归纳法(GRI)的关联规则算法对数据进行分析.从年龄、性别支持度,不同不良反应现象与不同年龄段间关联关系的置信度以及不同不良反应现象与不同性别间关联关系的置信度进行分析,得出相关结果.结果与结论 药品不良反应主要发生在2个年龄段,一是50~59岁年龄段,不良反应主要为咳嗽和头晕;二是60~69岁年龄段,不良反应主要为头晕和恶心.药品不良反应在男性身上发生的频次较女性多;个别不良反应有较明显的性别偏向.%OBJECTIVE: To explore potential correlation of adverse drug reaction (ADR) with patient's gender and age, and to provide the best evidence for medical staff to making decision to ensure that security of drug use for cardiovascular and cerebro-vascular diseases and improve therapeutic efficacy. METHODS: 9 640 ADR reports on drug use for cardiovascular and cerebrovas-cular diseases were collected from Jiangsu Province Adverse Drug Reaction Monitoring Centre during 2004 - 2009. GRI association rules algorithm of data mining technology was used for data analysis. RESULTS: During 2004-2009, data was analyzed from support of age and gender, confidence level of association of different ADR phenomena with different age groups and confidence level of association of different ADR phenomenon with gender. Related results were obtained. CONCLUSION: The ADR mainly occurred in two age groups, 50~59 age group and ADR included coughing and dizziness; 60~69 age group and ADR included dizziness and nausea. ADR occurred in more male than female; individual ADR were more obvious gender bias, such as cough mainly in

  16. Remodeling A School Shop?

    Science.gov (United States)

    Baker, G. E.

    1970-01-01

    Presents guidelines for remodeling a school shop combining major considerations of funds, program changes, class management, and flexibility, with the needs of wiring, painting, and placement of equipment. (Author)

  17. Anti-CCL21 Antibody Attenuates Infarct Size and Improves Cardiac Remodeling After Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Yi Jiang

    2015-09-01

    Full Text Available Background/Aims: Over-activation of cellular inflammatory effectors adversely affects myocardial function after acute myocardial infarction (AMI. The CC-chemokine CCL21 is, via its receptor CCR7, one of the key regulators of inflammation and immune cell recruitment, participates in various inflammatory disorders, including cardiovascular ones. This study explored the therapeutic effect of an anti-CCL21 antibody in cardiac remodeling after myocardial infarction. Methods and Results: An animal model of AMI generated by left anterior descending coronary artery ligation in C57BL/6 mice resulted in higher levels of circulating CCL21 and cardiac CCR7. Neutralization of CCL21 by intravenous injection of anti-CCL21 monoclonal antibody reduced infarct size after AMI, decreased serum levels of neutrophil and monocyte chemo attractants post AMI, diminished neutrophil and macrophage recruitment in infarcted myocardium, and suppressed MMP-9 and total collagen content in myocardium. Anti-CCL21 treatment also limited cardiac enlargement and improved left ventricular function. Conclusions: Our study indicated that CCL21 was involved in cardiac remodeling post infarction and anti-CCL21 strategies might be useful in the treatment of AMI.

  18. Myocardial Tissue Remodeling in Adolescent Obesity

    OpenAIRE

    Shah, Ravi V.; Abbasi, Siddique A.; Neilan, Tomas G; Hulten, Edward; Coelho‐Filho, Otavio; Hoppin, Alison; Levitsky, Lynne; de Ferranti, Sarah; Rhodes, Erinn T.; Traum, Avram; Goodman, Elizabeth; Feng, Henry; Heydari, Bobak; Harris, William S.; Hoefner, Daniel M.

    2013-01-01

    Background: Childhood obesity is a significant risk factor for cardiovascular disease in adulthood. Although ventricular remodeling has been reported in obese youth, early tissue‐level markers within the myocardium that precede organ‐level alterations have not been described. Methods and Results: We studied 21 obese adolescents (mean age, 17.7±2.6 years; mean body mass index [BMI], 41.9±9.5 kg/m2, including 11 patients with type 2 diabetes [T2D]) and 12 healthy volunteers (age, 15.1±4.5 years...

  19. Electrical and myocardial remodeling in primary aldosteronism

    Directory of Open Access Journals (Sweden)

    Mario eCurione

    2014-11-01

    Full Text Available Objective and design: primary aldosteronism (PA represents the most common cause of secondary hypertension. An higher risk of cardiovascular events has been reported in patients with PA than otherwise similar patients with essential hypertension (EH. At today few studies has been investigated the electrocardiographic changes in PA patients compared to EH patients.Methods: to investigate the electrocardiographic changes and heart remodeling in PA we enrolled 61 consecutive patients, 30 with PA (12 with aldosterone producing adenoma-APA and 18 with bilateral adrenal hyperplasia-IHA and 30 with EH. In all subjects electrelectrocardiographic parameters were evaluated from 12-lead electrocardiograms and heart remodeling with echocardiogram.Results: no significant differences in age, sex , body mass index (BMI and blood pressure were found in two groups. The P wave and PR interval duration were significantly prolonged in patientswith PA respect to EH (p< 0.003 and p< 0.002, respectively. First degree atrioventricular block was present in 16% patient with PA and only in 3.2% patients with EH. In PA patients the interventricular septum thickness (IVST correlated with left ventricular mass indecized (LVMi (r= 0.54; p< 0.04, and with PR duration (r= 0.51; p< 0.03. Left ventricular hypertrophy (LVH was present in 53% patients with PA and in 26% patients with EH (χ2 p<0.03.Conclusions: in this case-control study, patients with PA show more anatomic and electrical heart remodeling than those with EH. We hypothesize that in patients with PA these cardiac changes may play a role for the increased risk of future cardiovascular events.

  20. Urotensin II in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    Fraser D Russell

    2008-08-01

    Full Text Available Fraser D RussellSchool of Health and Sport Sciences, Faculty of Science, Health and Education, University of the Sunshine Coast, Sippy Downs, Queensland, AustraliaAbstract: Cardiovascular function is modulated by neuronal transmitters, circulating hormones, and factors that are released locally from tissues. Urotensin II (UII is an 11 amino acid peptide that stimulates its’ obligatory G protein coupled urotensin II receptors (UT to modulate cardiovascular function in humans and in other animal species, and has been implicated in both vasculoprotective and vasculopathic effects. For example, tissue and circulating concentrations of UII have been reported to increase in some studies involving patients with atherosclerosis, heart failure, hypertension, preeclampsia, diabetes, renal disease and liver disease, raising the possibility that the UT receptor system is involved in the development and/or progression of these conditions. Consistent with this hypothesis, administration of UT receptor antagonists to animal models of cardiovascular disease have revealed improvements in cardiovascular remodelling and hemodynamics. However, recent studies have questioned this contributory role of UII in disease, and have instead postulated a protective effect on the cardiovascular system. For example, high concentrations of circulating UII correlated with improved clinical outcomes in patients with renal disease or myocardial infarction. The purpose of this review is to consider the regulation of the cardiovascular system by UII, giving consideration to methodologies for measurement of plasma concentrations, sites of synthesis and triggers for release.Keywords: urotensin II, cardiovascular disease, heart failure, hypertension

  1. Antihypertension and anti-cardiovascular remodeling by phenylalanine in spontaneously hypertensive rats: effectiveness and mechanisms%苯丙氨酸对自发性高血压大鼠的抗高血压和抗心血管重塑的效果和机制

    Institute of Scientific and Technical Information of China (English)

    赵光胜; 李振波; 顾天华

    2001-01-01

    目的 阐明苯丙氨酸(phe)在自发性高血压大鼠(SHR)中的抗高血压和抗心血管重塑的效果和机制。 方法 4-6周龄SHRs鼠用或不用3% phe的饲料进行干预,比较两组间血压及心血管变化。用VIDAS数字式视频处理技术、光学显微镜及透射电镜检测心血管结构变化。测量胸主动脉平滑肌细胞(CASMCs)的[3H]胸腺嘧啶放射性计数(cpm)和用结晶紫染色法测量细胞数目。Smith法测定Ca2+内流,Grynkic法测量[Ca2+]i。心肌总mRNA进行Northern blot分析。HPLC法测定酪氨酸羟化酶(TH)活性。用HPLC测定脑组织儿茶酚胺含量。 静脉注射3H-L-phe(1ml/kg)后进行动力学计算。测定和比较CASMCs对3H-L-phe的摄取。 结果 Phe能(1)阻止血压和心重/体重比值随年龄的增加。减少SHR-phe组大鼠主动脉中层厚度和胶原含量;(2)抑制胶原α2(I)mRNA、c-fos和c-myc表达;降低细胞内[Ca2+]i;增高尾核TH活性和下丘脑肾上腺素含量;(3)部分逆转phe动力学异常。 结论 幼龄SHR鼠用Phe干预具有抗高血压和抗心血管重塑作用。机制可能是:直接抑制心血管细胞生长;降低中枢交感神经活性;逆转phe的代谢异常和降低细胞内[Ca2+]i。%Objective To investigate mechanisms of anti-hypertension and anti-cardiovascular remodeling by phenylalanine (phe) in spontaneously hypertensive rats (SHRs). Methods The comparison of blood pressure (BP) increment with the ages and cardiovascular changes of SHRs was made between the 3% phe-intervented group (SHR-phe) and the control SHRs group. Detection of the structural changes with the VIDAS digital vedio-frequency processing technique and light and electron microscopy were made. The cell growth and proliferation of cultured smooth muscle cells (CSMCs) of the thoracic aortas or myocardial fibroblasts were evaluated by measuring the 3 H-thymidine counts per minute (cpm) incorporated into the new

  2. Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer

    NARCIS (Netherlands)

    Han, Y.W.; Houcken, W.; Loos, B.G.; Schenkein, H.A.; Tezal, M.

    2014-01-01

    Interrelationships between periodontal infection and systemic conditions such as cardiovascular disease, adverse pregnancy outcomes, and head-and-neck cancer have become increasingly appreciated in recent years. Periodontitis is associated with cardiovascular disease (CVD) and, experimentally, with

  3. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    2017-01-01

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance?

  4. Advances in stem cell therapy for cardiovascular disease (Review).

    Science.gov (United States)

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  5. Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Xian-Liang Tang

    Full Text Available Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI. Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14 received oral atorvastatin (10 mg/kg/d daily for 3 wk before and 4 wk after MI, while group I (n = 12 received equivalent doses of vehicle. Infarct size (Masson's trichrome-stained sections was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF and fractional area change (FAC were higher while LV end-diastolic volume (LVEDV and LV end-systolic and end-diastolic diameters (LVESD and LVEDD were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt(max, end-systolic elastance (Ees, and preload recruitable stroke work (PRSW and lower LV end-diastolic pressure (LVEDP. Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.

  6. Remodeling with the sun

    Energy Technology Data Exchange (ETDEWEB)

    Bodzin, S. [ed.

    1997-05-01

    Remodeling is the perfect time to improve daylighting, direct gain heating and shading with passive solar techniques. It can also provide the best opportunity to add solar water heating or even photoboltaics to a home. This article describes addition of such energy efficient plans to a home in terms of what is needed and what the benefits are: adding windows, North glass, east and west glass, south glass, daylighting, the roof, shingles and roofing tiles, walls and floors, solar hot water, photovoltaics. Two side bars discuss the sunplace: a passive solar room and angles and overhangs.

  7. Adverse effects of statins - myths and reality.

    Science.gov (United States)

    Šimić, Iveta; Reiner, Željko

    2015-01-01

    Statins reduce cardiovascular mortality and morbidity as well as cardiovascular events in patients with a very high risk of cardiovascular disease (CVD) and also in subjects with high or moderate risk by reducing the levels of low-density lipoprotein cholesterol (LDL-C). Although they are considered to be drugs with a very good safety profile, because of their wide use there are many concerns that their adverse effects might compromise their proven beneficial effects. Therefore this article reviews all the data and provides an evidence- based insight what are the proven adverse effects of statins and what are the "myths" about them. The most important side effects include myopathy and rhabdomyolysis. Another side effect is increased activity of liver tests which occurs occasionally and is reversible. However, recent studies even suggest that statin therapy can improve hepatic steatosis. It is beyond any doubt that statins do slightly increase the incidence of type 2 diabetes mellitus in people with two or more components of metabolic syndrome but the cardiovascular benefits of such a treatment by far exceed this risk. Statin therapy has also been associated with some adverse renal effects, eg. acute renal failure, but recent data suggest even a possible protective effect of these drugs on renal dysfunction. Concerns that statins might increase cancer have not been proven. On the contrary, several studies have indicated a possible benefit of these drugs in patients with different types of cancer. Early concerns about cognitive dysfunction and memory loss associated with statins use could not be proven and most recent data even suggest a possible beneficial effect of statins in the prevention of dementia. Systematic reviews and clinical guidelines suggest that the cardiovascular benefits of statins by far out-weight non-cardiovascular harms in patients with cardiovascular risk.

  8. Cardiovascular Deconditioning

    Science.gov (United States)

    Charles, John B.; Fritsch-Yelle, Janice M.; Whitson, Peggy A.; Wood, Margie L.; Brown, Troy E.; Fortner, G. William

    1999-01-01

    Spaceflight causes adaptive changes in cardiovascular function that may deleteriously affect crew health and safety. Over the last three decades, symptoms of cardiovascular changes have ranged from postflight orthostatic tachycardia and decreased exercise capacity to serious cardiac rhythm disturbances during extravehicular activities (EVA). The most documented symptom of cardiovascular dysfunction, postflight orthostatic intolerance, has affected a significant percentage of U.S. Space Shuttle astronauts. Problems of cardiovascular dysfunction associated with spaceflight are a concern to NASA. This has been particularly true during Shuttle flights where the primary concern is the crew's physical health, including the pilot's ability to land the Orbiter, and the crew's ability to quickly egress and move to safety should a dangerous condition arise. The study of astronauts during Shuttle activities is inherently more difficult than most human research. Consequently, sample sizes have been small and results have lacked consistency. Before the Extended Duration Orbiter Medical Project (EDOMP), there was a lack of normative data on changes in cardiovascular parameters during and after spaceflight. The EDOMP for the first time allowed studies on a large enough number of subjects to overcome some of these problems. There were three primary goals of the Cardiovascular EDOMP studies. The first was to establish, through descriptive studies, a normative data base of cardiovascular changes attributable to spaceflight. The second goal was to determine mechanisms of cardiovascular changes resulting from spaceflight (particularly orthostatic hypotension and cardiac rhythm disturbances). The third was to evaluate possible countermeasures. The Cardiovascular EDOMP studies involved parallel descriptive, mechanistic, and countermeasure evaluations.

  9. To Remodel or To Build?

    Science.gov (United States)

    Rosenblum, Todd

    2009-01-01

    The question of remodeling an existing house to make it wheelchair accessible or building a new barrier-free house is a difficult decision. This article presents some initial questions and considerations followed by a list of pros and cons for remodeling an existing house vs. building a new house.

  10. 心脑血管疾病用药不良反应与药品品种关系的聚类分析%Cluster Analysis on The Adverse Drug Reactions Caused by Medication Used for Cardiovascular Disease and Cerebrovascular Disease According to The Varieties of Drugs

    Institute of Scientific and Technical Information of China (English)

    冯变玲; 杨世民; 蓝夏璐; 魏芬; 尤海生

    2011-01-01

    目的 寻找心脑血管疾病用药的不良反应与药品品种间聚类关系,促进临床安全合理用药.方法 运用数据挖掘技术中的两阶段聚类算法对药品的严重不良反应与药品品种间的关系进行聚类分析.结果由聚类结果可知,在使用心脑血管疾病用药时,出现的严重和新的严重不良反应为肝功能异常、肾功能异常、呼吸困难、横纹肌溶解,导致这些严重不良反应的药物有受体类药物、钙离子拮抗剂、降低胆固醇类药物.结论在选择心脑血管疾病用药时,受体类药物、钙离子拮抗剂、降低胆固醇类药物应慎用、少用,尽量避免严重的不良反应发生.%Objective To identify the clustering relations between adverse drug reactions (ADRs) with different varieties of drugs to assist medical staff to deal with safe and efficacious mediation. Methods Applying a two- stage clustering algorithm of data mining to conduct cluster analysis on the severe adverse events caused by medication used for cardiovascular disease and cerebrovascular disease according to the varieties of drugs. Results New and severe adverse events including dysfunction of liver, renal dysfunction, dyspnea and rhabdomyolysis are usually caused by receptor drugs, calcium antagonists and cholesterol- lowering drugs. Conclusions To avoid serious adverse events, receptor drugs, calcium antagonists and cholesterol-lowering drugs should be used prudently or seldom used in the medication used for cardiovascular disease and cerebrovascular disease.

  11. 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.

  12. Genetic influences on cardiovascular stress reactivity

    NARCIS (Netherlands)

    Wu, Ting; Snieder, Harold; de Geus, Eco

    2010-01-01

    Individual differences in the cardiovascular response to stress play a central role in the reactivity hypothesis linking frequent exposure to psychosocial stress to adverse outcomes in cardiovascular health. To assess the importance of genetic factors, a meta-analysis was performed on all published

  13. Development of Extracorporeal Shock Wave Therapy for the Treatment for Ischemic Cardiovascular Diseases

    Science.gov (United States)

    Shimokawa, Hiroaki

    Cardiovascular diseases, such as coronary artery disease and peripheral artery disease, are the major causes of death in developed countries, and the number of elderly patients has been rapidly increasing worldwide. Thus, it is crucial to develop new non-invasive therapeutic strategies for these patients. We found that a low-energy shock wave (SW) (about 10% of the energy density that is used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Subsequently, we demonstrated that extracorporeal cardiac SW therapy with low-energy SW up-regulates the expression of VEGF, enhances angiogenesis, and improves myocardial ischemia in a pig model of chronic myocardial ischemia without any adverse effects in vivo. Based on these promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic therapy with low-energy SW for cardiovascular diseases. Our extracorporeal cardiac SW therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe coronary artery disease without indication of percutaneous coronary intervention or coronary artery bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction in pigs and in enhancing angiogenesis in hindlimb ischemia in animals and patients with coronary artery disease. Furthermore, our recent experimental studies suggest that the SW therapy is also effective for indications other than cardiovascular diseases. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic strategy for cardiovascular medicine.

  14. Association of hypoglycemic treatment regimens with cardiovascular outcomes in overweight and obese subjects with type 2 diabetes

    DEFF Research Database (Denmark)

    Ghotbi, Adam Ali; Køber, Lars; Finer, Nick;

    2013-01-01

    To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk.......To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk....

  15. 糖尿病患者P物质含量与围手术期不良心血管事件的相关性研究%Correlative study on the substance P contents with perioperative adverse cardiovascular events in diabetic patients

    Institute of Scientific and Technical Information of China (English)

    王利平; 张瑞林; 郭政

    2016-01-01

    目的 探讨糖尿病患者血清P物质(substance P,SP)含量变化与围手术期不良心血管事件(adverse cardiovascular event,ACVE)的相关性. 方法 择期行胆囊切除术的患者44例,根据术前有无糖尿病分为两组(每组22例):糖尿病组(DM组)与对照组(C组).记录两组患者术前一般情况(年龄、性别、ASA分级、体重、血脂、肌酐等),术中血糖、心律、HR、BP、ECG、手术时间以及补液量等变化.采用ELISA法测定术前、术毕SP含量以及术前、术后24 h肌钙蛋白Ⅰ(cardiac troponin Ⅰ,cTnⅠ)含量. 结果 DM组患者胆囊切除术围手术期ACVE发生率(68.18%)较C组(36.36%)高(P<0.05);DM组患者术前、术毕血清SP含量[(1.1 ±0.4)、(1.0±0.5) μg/L]较C组[(1.6±o.7)、(1.3±o.6)ug/L]低(P<0.05),而术前、术后24 h血清cTnⅠ含量[(1.8±0.6)、(2.4±1.0)μg/L]较C组[(1.2±0.5)、(1.4±0.6)μg/L]高(P<0.05);根据围手术期有无发生ACVE进行分类,发生ACVE患者SP含量[(1.0±0.5)μg/L]较未发生ACVE患者(non-ACVE,NACVE)SP含量[(1.4±0.7)μg/L]低(P<0.05).结论 糖尿病患者血清SP含量降低可能与患者围手术期ACVE的发生率有关.%Objective The aim of the study was to investigate the association of reduction of serum substance P (SP) with increase in perioperative adverse cardiovascular events (ACVE) in diabetic patients.Methods Forty-four patients who underwent cholecystectomy were divided into control group (group C) and diabetes mellitus group (group DM)(n=22).The general characteristics,including age,gender,ASA grade,body weight,serum lipids,serum creatinine before the operation were analyzed.During the operation,heart rhythm,HR,ST-segment BP and ECG were monitored and the blood glucose,the volume of bleeding and the intravenous infusion were recorded.The content of serum SP (at pre-operation and the end-operation) and cardiac troponin Ⅰ (cTnⅠ),at pre-operation and at 24 h after-operation were examined by ELISA.Results The

  16. Stress and atherosclerotic cardiovascular disease.

    Science.gov (United States)

    Inoue, Nobutaka

    2014-01-01

    Recent major advances in medical science have introduced a wide variety of treatments against atherosclerosis-based cardiovascular diseases, which has led to a significant reduction in mortality associated with these diseases. However, atherosclerosis-based cardiovascular disease remains a leading cause of death. Furthermore, progress in medical science has demonstrated the pathogenesis of cardiovascular disease to be complicated, with a wide variety of underlying factors. Among these factors, stress is thought to be pivotal. Several types of stress are involved in the development of cardiovascular disease, including oxidative stress, mental stress, hemodynamic stress and social stress. Accumulating evidence indicates that traditional risk factors for atherosclerosis, including diabetes, hyperlipidemia, hypertension and smoking, induce oxidative stress in the vasculature. Oxidative stress is implicated in the pathogenesis of endothelial dysfunction, atherogenesis, hypertension and remodeling of blood vessels. Meanwhile, mental stress is a well-known major contributor to the development of cardiovascular disease. The cardiovascular system is constantly exposed to hemodynamic stress by the blood flow and/or pulsation, and hemodynamic stress exerts profound effects on the biology of vascular cells and cardiomyocytes. In addition, social stress, such as that due to a lack of social support, poverty or living alone, has a negative impact on the incidence of cardiovascular disease. Furthermore, there are interactions between mental, oxidative and hemodynamic stress. The production of reactive oxygen species is increased under high levels of mental stress in close association with oxidative stress. These stress responses and their interactions play central roles in the pathogenesis of atherosclerosis-based cardiovascular disease. Accordingly, the pathophysiological and clinical implications of stress are discussed in this article.

  17. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    DEFF Research Database (Denmark)

    Østrup, Olga; Hyttel, Poul; Klærke, Dan Arne;

    2011-01-01

    . This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling...... complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract......Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression...

  18. 有氧运动对大鼠心血管和胸主动脉平滑肌的功能重塑作用%Functional Remodeling of the Aerobic Exercise on the Cardiovascular System and Thoracic Aortic Smooth Muscle of Rats

    Institute of Scientific and Technical Information of China (English)

    石丽君; 李珊珊; 熊开宇; 龚丽景

    2011-01-01

    Objective: To investigate the aerobic exercise-induced functional remodeling of the rat cardiovascular systmem and thoracic aortic smooth muscle,and to explore the possible potassium channel mechanisms underlying these effects.Methods: 20 male Wistar rats(2M) were randomly divided into sedentary group and exercise group.Training protocol: 8 week treadmill.After 8 weeks,some animals(n=5 in each group) underwent femoral arterial and venous cannulation.Catheters were tunneled subcutaneously,exteriorized at the nape of the neck.Following one day recovery,the basal blood pressure,heart rate and the cardiovascular responses to intravenous(i.v.) injection of Ang II and non-specific K+ channel blocker TEA were monitored in vivo.In the other 10 animals,the thoracic aorta was carefully exposed after thoracotomy and dissected free.Segments were cut into rings and the endothelial cell lining was removed.The vessel contractility was examined in vitro.Results:1) After the aerobic exercises,the heart rate at rest reduced significantly.The mean arterial pressure of rats had a tendency to decrease but there was no significant difference between the sedentary and the exercise groups at rest.2)The pressor responses induced by i.v.injection of Ang II were attenuated in the exercise group compared with that in the sedentary group;3) The pressor responses induced by i.v.injection of TEA,was significantly enhanced after exercise training;4)Ang II(10-9~10-4M) caused a significantly increase of vascular tone in a concentration-dependent manner in both groups,while the increase amplitude was less in exercise group than in the sedentary group;5) TEA(5×10-3 M) could induce an increase of vessel contractility in two groups,while the amplitude of increase was significantly enhanced after exercise training.Conclusion: Aerobic exercise training can induce functional remodeling of the rat cardiovascular system and thoracic aorta smooth muscle,in which

  19. Role of arginase in vessel wall remodeling

    Directory of Open Access Journals (Sweden)

    William eDurante

    2013-05-01

    Full Text Available Arginase metabolizes the semi-essential amino acid L-arginine to L-ornithine and urea. There are two distinct isoforms of arginase, arginase I and II, which are encoded by separate genes and display differences in tissue distribution, subcellular localization, and molecular regulation. Blood vessels express both arginase I and II but their distribution appears to be cell-, vessel-, and species-specific. Both isoforms of arginase are induced by numerous pathologic stimuli and contribute to vascular cell dysfunction and vessel wall remodeling in several diseases. Clinical and experimental studies have documented increases in the expression and/or activity of arginase I or II in blood vessels following arterial injury and in pulmonary and arterial hypertension, aging, and atherosclerosis. Significantly, pharmacological inhibition or genetic ablation of arginase in animals ameliorates abnormalities in vascular cells and normalizes blood vessel architecture and function in all of these pathological states. The detrimental effect of arginase in vascular remodeling is attributable to its ability to stimulate vascular smooth muscle cell and endothelial cell proliferation, and collagen deposition by promoting the synthesis of polyamines and L-proline, respectively. In addition, arginase adversely impacts arterial remodeling by directing macrophages towards an inflammatory phenotype. Moreover, the proliferative, fibrotic, and inflammatory actions of arginase in the vasculature are further amplified by its capacity to inhibit nitric oxide synthesis by competing with nitric oxide synthase for substrate, L-arginine. Pharmacologic or molecular approaches targeting specific isoforms of arginase represent a promising strategy in treating obstructive fibroproliferative vascular disease.

  20. Remodelling of the microarchitecture of resistance arteries in cardiovascular diseases

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Brewer, Jonathan R.; Leurgans, Thomas;

    is largely unknown, and the presented project aims to investigate this. Innovative multiphoton excitation microscopy will be applied on live (vital), isolated, cannulated and pressurized arteries from parietal pericardial biopsies obtained during open cardiac surgery (coronary artery bypass grafting......, and endothelial and smooth muscle cells will be determined in relation to a range of distending pressures (50, 100, 150, 200 mmHg) and in relation to the frequently determined M:L. We present here our initial results from (pig) pericardial biopsies where we describe the microarchitecture of the tissue...... in comparison to other well-studied microvascular beds (e.g. rat mesentery). In the future we aim to compare the microarchitecture of small resistance arteries from parietal pericardial biopsies between patients with and without (treated) hypertension, diabetes and/or ischemic heart disease. 1. Buus, N.H., et...

  1. Risk of Bias in Systematic Reviews of Non-Randomized Studies of Adverse Cardiovascular Effects of Thiazolidinediones and Cyclooxygenase-2 Inhibitors: Application of a New Cochrane Risk of Bias Tool.

    Directory of Open Access Journals (Sweden)

    Anja Bilandzic

    2016-04-01

    Full Text Available Systematic reviews of the effects of healthcare interventions frequently include non-randomized studies. These are subject to confounding and a range of other biases that are seldom considered in detail when synthesizing and interpreting the results. Our aims were to assess the reliability and usability of a new Cochrane risk of bias (RoB tool for non-randomized studies of interventions and to determine whether restricting analysis to studies with low or moderate RoB made a material difference to the results of the reviews.We selected two systematic reviews of population-based, controlled non-randomized studies of the relationship between the use of thiazolidinediones (TZDs and cyclooxygenase-2 (COX-2 inhibitors and major cardiovascular events. Two epidemiologists applied the Cochrane RoB tool and made assessments across the seven specified domains of bias for each of 37 component studies. Inter-rater agreement was measured using the weighted Kappa statistic. We grouped studies according to overall RoB and performed statistical pooling for (a all studies and (b only studies with low or moderate RoB. Kappa scores across the seven bias domains ranged from 0.50 to 1.0. In the COX-2 inhibitor review, two studies had low overall RoB, 14 had moderate RoB, and five had serious RoB. In the TZD review, six studies had low RoB, four had moderate RoB, four had serious RoB, and two had critical RoB. The pooled odds ratios for myocardial infarction, heart failure, and death for rosiglitazone versus pioglitazone remained significantly elevated when analyses were confined to studies with low or moderate RoB. However, the estimate for myocardial infarction declined from 1.14 (95% CI 1.07-1.24 to 1.06 (95% CI 0.99-1.13 when analysis was confined to studies with low RoB. Estimates of pooled relative risks of cardiovascular events with COX-2 inhibitors compared with no nonsteroidal anti-inflammatory drug changed little when analyses were confined to studies with

  2. 10523例心血管药物不良反应报告分析%Analysis of 10523 Cases of Adverse Drug Reaction of Cardiovascular A-gents

    Institute of Scientific and Technical Information of China (English)

    张桂香

    2015-01-01

    抽取湖南省上报国家不良反应中心的10523 份心血管药物不良反应报告,按患者年龄、给药途径、药品种类、涉及器官或系统、临床表现及转归等进行统计、分析. 结果显示:静脉滴注较其它给药途径更易发生ADR (5375 例,占51.1%);降压药引发 ADR 的比例最高(4052例,占59.3%);ADR 的临床表现以头痛、头晕等神经系统损害为主. 应加强心血管药物ADR 监测,减少 ADR的发生,促进临床合理用药.%The data of a total of 10523 ADR cases from Hunan were analyzed according to age,route of ad-ministration, types of drug and organ systems in-volved.The results showed that ADR cases caused by intravenous drip was the most (5375 cases,51.1%);ADR cases were mainly caused by antihypertensive a-gents ( 4052 cases, 59.3%); The ADR manifested mainly as lesions of Nervous system.Medical staff must strengthen the monitoring of ADR in cardiovascular a-gents to promote rational use of drug and reduce the in-cidence of ADR.

  3. Correlation between paraoxonase 1 Q192R polymorphism and cardiovascular adverse events after treatment with clopidogrel: a Meta-analysis%对氧磷酶1 Q192R基因多态性与氯吡格雷治疗后心血管不良事件相关性的Meta分析

    Institute of Scientific and Technical Information of China (English)

    李新刚; 赵坤; 鲁燕侠; 赵志刚; 刘振华

    2015-01-01

    目的 评价对氧磷酶1(paraoxonase 1 ,PON1) Q192R基因多态性与氯吡格雷治疗后发生心血管不良事件的相关性. 方法 检索Web of Knowledge、PubMed、ScienceDirect、Embase、Cochrane Library,中国知网、万方数据库和维普中文科技期刊数据库(建库到2015年3月),收集符合纳入标准的前瞻性队列研究,采用Review Manager 5.3软件进行Meta分析.结果 采用比值比(OR)及其95%置信区间(CI)表示. 结果共有12项研究纳入Meta分析,患者共10 090例,其中亚洲人2 113例、欧洲人7 396例,北美洲人581例;PON1 Q192R基因型为QQ者4 096例,QR+ RR者5 994例.研究质量评价结果均为高质量.亚洲人群亚组中PON1 192QQ基因型者心血管事件发生率为8.1% (38/472),QR+ RR基因型者为10.8%(177/1 641),OR=1.06,95% CI为0.64 ~ 1.75,P=0.82;北美洲人群亚组中PON1 192QQ基因型者心血管事件发生率为10.4% (27/260),QR+ RR基因型者为10.9% (35/321),OR =0.95,95% CI为0.56 ~ 1.63,P=0.42;欧洲人群亚组中PON1 192QQ基因型者心血管事件发生率为6.5% (217/3 364),QR+ RR基因型者为5.6% (225/4 032),OR=1.21,95% CI为0.85 ~ 1.73,P=0.28.3个亚组合并后,PON1 192QQ基因型者心血管事件发生率为6.9% (282/4 096),QR+ RR基因型者为7.3% (437/5 994),OR=1.13,95% CI为0.89 ~ 1.44,P=0.33.漏斗图分析表明纳入研究不存在明显的发表偏倚或选择性偏倚. 结论 PON1 Q192R基因多态性与氯吡格雷治疗后的心血管不良事件之间没有明显相关性.%Objective To evaluate the correlation between paraoxonase 1 (PON1) Q192R polymorphism and cardiovascular adverse events in patients treated with clopidogrel.Methods Web of Knowledge, PubMed, ScienceDirect, Embase, Cochrane Library, China National Knowledge Infrastructure,Wanfang, and CQVIP were searched from the inception to March 2015 and prospective cohort studies in accordance with the criteria were collected.Meta-analysis was performed using Rev

  4. Cardiovascular risks associated with low dose ionizing particle radiation.

    Directory of Open Access Journals (Sweden)

    Xinhua Yan

    Full Text Available Previous epidemiologic data demonstrate that cardiovascular (CV morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton ((1H; 0.5 Gy, 1 GeV and iron ion ((56Fe; 0.15 Gy, 1GeV/nucleon irradiation with and without an acute myocardial ischemia (AMI event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in (56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, (56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

  5. Classification and Prognostic Evaluation of Left Ventricular Remodeling in Patients With Asymptomatic Heart Failure.

    Science.gov (United States)

    Pugliese, Nicola Riccardo; Fabiani, Iacopo; La Carrubba, Salvatore; Conte, Lorenzo; Antonini-Canterin, Francesco; Colonna, Paolo; Caso, Pio; Benedetto, Frank; Santini, Veronica; Carerj, Scipione; Romano, Maria Francesca; Citro, Rodolfo; Di Bello, Vitantonio

    2017-01-01

    Patients with asymptomatic heart failure (HF; stage A and B) are characterized by maladaptive left ventricular (LV) remodeling. Classic 4-group classification of remodeling considers only LV mass index and relative wall thickness as variables. Complex remodeling classification (CRC) includes also LV end-diastolic volume index. Main aim was to assess the prognostic impact of CRC in stage A and B HF. A total of 1,750 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. LV dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated, together with LV remodeling. We considered a composite end point: all-cause death, myocardial infarction, coronary revascularizations, cerebrovascular events, and acute pulmonary edema. CRC was suitable for 1,729 patients (men 53.6%; age 58.3 ± 13 years). Two hundred thirty-eight patients presented systolic dysfunction (ejection fraction remodeling, 47 eccentric remodeling, 350 concentric hypertrophy, 29 mixed hypertrophy, 86 dilated hypertrophy, and 53 eccentric hypertrophy. Age and gender distribution was noticed (p remodeling classification, systolic, and diastolic dysfunction), CRC was independent predictor of primary end point (p = 0.044, hazard ratio 1.101, 95% CI 1.003 to 1.21), confirmed in a logistic regression (p <0.03). In conclusion, CRC could help physicians in prognostic stratification of patients in stage A and B HF.

  6. Depressive Symptoms, Health Behaviors, and Risk of Cardiovascular Events in Patients With Coronary Heart Disease

    NARCIS (Netherlands)

    Whooley, Mary A.; de Jonge, Peter; Vittinghoff, Eric; Otte, Christian; Moos, Rudolf; Carney, Robert M.; Ali, Sadia; Dowray, Sunaina; Na, Beeya; Feldman, Mitchell D.; Schiller, Nelson B.; Browner, Warren S.

    2008-01-01

    Context Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown. Objective To determine why depressive symptoms are associated with an increased risk of cardiovascular events. Design and Part

  7. Regulation of CaMKII signaling in cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Mariya Yordanova Mollova

    2015-08-01

    Full Text Available Heart failure (HF is a major cause of death in the developed countries. (Murray and Lopez, 1996;Koitabashi and Kass, 2012. Adverse cardiac remodeling that precedes heart muscle dysfunction is characterized by a myriad of molecular changes affecting the cardiomyocyte. Among these, alterations in protein kinase pathways play often an important mediator role since they link upstream pathologic stress signaling with downstream regulatory programs and thus affect both the structural and functional integrity of the heart muscle. In the context of cardiac disease, a profound understanding for the overriding mechanisms that regulate protein kinase activity (protein-protein interactions, post-translational modifications, or targeting via anchoring proteins is crucial for the development of specific and effective pharmacological treatment strategies targeting the failing myocardium.In this review, we focus on several mechanisms of upstream regulation of Ca2+/Calmodulin-dependent kinase II (CaM Kinase II, CaMKII that play a relevant pathophysiological role in the development and progression of cardiovascular disease; precise targeting of these mechanisms might therefore represent novel and promising tools for prevention and treatment of HF.

  8. Social factors and cardiovascular morbidity.

    Science.gov (United States)

    Brunner, Eric John

    2017-03-01

    Recent progress in population health at aggregate level, measured by life expectancy, has been accompanied by lack of progress in reducing the difference in health prospects between groups defined by social status. Cardiovascular disease is an important contributor to this undesirable situation. The stepwise gradient of higher risk with lower status is accounted for partly by social gradients in health behaviors. The psychosocial hypothesis provides a stronger explanation, based on social patterning of living and working environments and psychological assets that individuals develop during childhood. Three decades of research based on Whitehall II and other cohort studies provide evidence for psychosocial pathways leading to cardiovascular morbidity and mortality. Job stress is a useful paradigm because exposure is long term and depends on occupational status. Studies of social-biological translation implicate autonomic and neuroendocrine function among the biological systems that mediate between chronic adverse psychosocial exposures and increased cardiometabolic risk and cardiovascular disease incidence.

  9. Microtissues in Cardiovascular Medicine: Regenerative Potential Based on a 3D Microenvironment

    Directory of Open Access Journals (Sweden)

    Julia Günter

    2016-01-01

    Full Text Available More people die annually from cardiovascular diseases than from any other cause. In particular, patients who suffer from myocardial infarction may be affected by ongoing adverse remodeling processes of the heart that may ultimately lead to heart failure. The introduction of stem and progenitor cell-based applications has raised substantial hope for reversing these processes and inducing cardiac regeneration. However, current stem cell therapies using single-cell suspensions have failed to demonstrate long-lasting efficacy due to the overall low retention rate after cell delivery to the myocardium. To overcome this obstacle, the concept of 3D cell culture techniques has been proposed to enhance therapeutic efficacy and cell engraftment based on the simulation of an in vivo-like microenvironment. Of great interest is the use of so-called microtissues or spheroids, which have evolved from their traditional role as in vitro models to their novel role as therapeutic agents. This review will provide an overview of the therapeutic potential of microtissues by addressing primarily cardiovascular regeneration. It will accentuate their advantages compared to other regenerative approaches and summarize the methods for generating clinically applicable microtissues. In addition, this review will illustrate the unique properties of the microenvironment within microtissues that makes them a promising next-generation therapeutic approach.

  10. Adverse cardiovascular effects of anabolic steroids : pathophysiology imaging

    NARCIS (Netherlands)

    Golestani, Reza; Slart, Riemer H. J. A.; Dullaart, Robin P. F.; Glaudemans, Andor W. J. M.; Zeebregts, Clark J.; Boersma, Hendrikus H.; Tio, Rene A.; Dierckx, Rudi A. J. O.

    2012-01-01

    Eur J Clin Invest 2012; 42 (7): 795803 Abstract Background Anabolic-androgenic steroids (AAS) are widely abused for enhancing muscle mass, strength, growth and improving athletic performance. Materials and methods In recent years, many observational and interventional studies have shown important ad

  11. The Role of Cardiolipin in Cardiovascular Health

    Directory of Open Access Journals (Sweden)

    Zheni Shen

    2015-01-01

    Full Text Available Cardiolipin (CL, the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria. The importance of CL in cardiovascular health is underscored by the life-threatening genetic disorder Barth syndrome (BTHS, which manifests clinically as cardiomyopathy, skeletal myopathy, neutropenia, and growth retardation. BTHS is caused by mutations in the gene encoding tafazzin, the transacylase that carries out the second CL remodeling step. In addition to BTHS, CL is linked to other cardiovascular diseases (CVDs, including cardiomyopathy, atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and Tangier disease. The link between CL and CVD may possibly be explained by the physiological roles of CL in pathways that are cardioprotective, including mitochondrial bioenergetics, autophagy/mitophagy, and mitogen activated protein kinase (MAPK pathways. In this review, we focus on the role of CL in the pathogenesis of CVD as well as the molecular mechanisms that may link CL functions to cardiovascular health.

  12. Remodeling of ribosomal genes in somatic cells by Xenopus egg extract

    Energy Technology Data Exchange (ETDEWEB)

    Ostrup, Olga, E-mail: osvarcova@gmail.com [Institute of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C (Denmark); Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo (Norway); Norwegian Center for Stem Cell Research, Oslo (Norway); Hyttel, Poul; Klaerke, Dan A. [Institute of Basic Animal and Veterinary Sciences, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C (Denmark); Collas, Philippe, E-mail: philc@medisin.uio.no [Stem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo (Norway); Norwegian Center for Stem Cell Research, Oslo (Norway)

    2011-09-02

    Highlights: {yields} Xenopus egg extract remodels nuclei and alter cell growth characteristics. {yields} Ribosomal genes are reprogrammed within 6 h after extract exposure. {yields} rDNA reprogramming involves promoter targeting of SNF2H remodeling complex. {yields} Xenopus egg extract does not initiate stress-related response in somatic cells. {yields} Aza-cytidine elicits a stress-induced response in reprogrammed cells. -- Abstract: Extracts from Xenopus eggs can reprogram gene expression in somatic nuclei, however little is known about the earliest processes associated with the switch in the transcriptional program. We show here that an early reprogramming event is the remodeling of ribosomal chromatin and gene expression. This occurs within hours of extract treatment and is distinct from a stress response. Egg extract elicits remodeling of the nuclear envelope, chromatin and nucleolus. Nucleolar remodeling involves a rapid and stable decrease in ribosomal gene transcription, and promoter targeting of the nucleolar remodeling complex component SNF2H without affecting occupancy of the transcription factor UBF and the stress silencers SUV39H1 and SIRT1. During this process, nucleolar localization of UBF and SIRT1 is not altered. On contrary, azacytidine pre-treatment has an adverse effect on rDNA remodeling induced by extract and elicits a stress-type nuclear response. Thus, an early event of Xenopus egg extract-mediated nuclear reprogramming is the remodeling of ribosomal genes involving nucleolar remodeling complex. Condition-specific and rapid silencing of ribosomal genes may serve as a sensitive marker for evaluation of various reprogramming methods.

  13. Exercise-Induced Cardiac Remodeling: Lessons from Humans, Horses, and Dogs

    Directory of Open Access Journals (Sweden)

    Rob Shave

    2017-02-01

    Full Text Available Physical activity is dependent upon the cardiovascular system adequately delivering blood to meet the metabolic and thermoregulatory demands of exercise. Animals who regularly exercise therefore require a well-adapted heart to support this delivery. The purpose of this review is to examine cardiac structure, and the potential for exercise-induced cardiac remodeling, in animals that regularly engage in strenuous activity. Specifically, we draw upon the literature that has studied the “athlete’s heart” in humans, horses, and dogs, to enable the reader to compare and contrast cardiac remodeling in these three athletic species. The available literature provides compelling evidence for exercise-induced cardiac remodeling in all three species. However, more work is required to understand the influence of species/breed specific genetics and exercise-related hemodynamics, in order to fully understand the impact of exercise on cardiac structure.

  14. 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.

  15. Effect of Administrative HDL-C Level on Adverse Cardiovascular Events After Discharge in Elder Patients With ST-segment Elevation Myocardial Infarction%老年ST段抬高型心肌梗死患者入院时高密度脂蛋白胆固醇水平对出院后不良心血管事件的影响研究

    Institute of Scientific and Technical Information of China (English)

    刘永; 葛华; 房玲

    2014-01-01

    Objective: To investigate the effect of administrative HDL-C (high density lipoprotein cholesterol) level on adverse cardiovascular events after discharge in elder patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 325 STEMI patients treated in our hospital from 2010-04 to 2012-07 were retrospectively studied. According to administrative HDL-C level, the patients were divided into 2 groups as High HDL-C group, n=139 and Low HDL-C group, n=186. The basic and clinical conditions, in-hospital treatment, death and the medication, adverse cardiovascular events during 6 and 12 months follow-up period were compared between 2 groups. Results: The patients with in-hospital reperfusion therapy was higher in Low HDL-C group, and Low HDL-C group had the higher ratio of emergent PCI treatment, all P Conclusion: The lower administrative HDL-C level in elder patients with STEMI had the higher risk of adverse cardiovascular events after discharge.%目的:探讨分析老年ST段抬高型心肌梗死(STEMI)患者入院时高密度脂蛋白胆固醇(HDL-C)水平对出院后心血管不良事件发生情况的影响。  方法:选取我院于2010-04至2012-07收治的325例老年STEMI患者,根据患者的HDL-C水平将其分为HDL-C高组(139例)与HDL-C低组(186例)。对比分析两组患者基线资料、临床资料、在院期间所接受的治疗、死亡情况、随访期间药物使用情况及不良心血管事件发生情况。  结果:HDL-C低组入院后接受再灌注治疗的比例高于HDL-C高组(P  结论:入院时HDL-C水平低的STEMI患者出院后发生不良心血管事件的风险更高。

  16. Relationship between vitamin D deficiency and cardiovascular disease

    OpenAIRE

    Ku, Yan-Chiou; Liu, Mu-En; Ku, Chang-Sheng; Liu, Ta-Yuan; Lin, Shoa-Lin

    2013-01-01

    Epidemiological studies have found that low 25-hydroxyvitamin D levels may be associated with coronary risk factors and adverse cardiovascular outcomes. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. In this review, we analyze the association between vitamin D supplementation and the reduction in cardiovascular disease. The role of v...

  17. Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment.

    Science.gov (United States)

    Palmeiro, Christopher; Davila, Maria I; Bhat, Mallika; Frishman, William H; Weiss, Irene A

    2013-01-01

    Subclinical hyperthyroidism (SHy), the mildest form of hyperthyroidism, is diagnosed in patients having a persistently low or undetectable serum concentration of thyroid-stimulating hormone (TSH) with normal free T4 and T3 concentrations. Although overt hyperthyroidism is associated with an increased risk of adverse cardiovascular outcomes, the cardiovascular risk of SHy is controversial. Multiple studies have demonstrated an increased risk of atrial fibrillation, especially in older individuals with TSH levels hyperthyroidism, and overall cardiovascular and osteoporotic fracture risks.

  18. Adverse outcomes after colposcopy

    Directory of Open Access Journals (Sweden)

    Damery Sarah L

    2011-01-01

    Full Text Available Abstract Background Colposcopy is an essential part of the National Health Service Cervical Screening Programme (NHSCSP. It is used for both diagnosis and treatment of pre-cancerous cells of the cervix. Despite colposcopy being a commonly performed and relatively invasive procedure, very little research has explored the potential long-term impacts of colposcopic examination upon patient quality of life. The aim of this study is to investigate and quantify any potential reduction in women's quality of life following a colposcopy procedure. More specifically, the degree of female sexual dysfunction and the excess risk of adverse events in those undergoing colposcopy will be explored. If such risks are identified, these can be communicated to women before undergoing colposcopy. It will also assist in identifying whether there are particular sub-groups at greater risk and if so, this may lead to a re-evaluation of current recommendations concerning colposcopically directed treatments. Methods/design Cohort study using postal surveys to assess sexual function and quality of life in women who have attended for colposcopy (cases, compared with those who have not attended colposcopy (controls. The prevalence and excess risk of female sexual dysfunction will be determined. Logistic regression will identify the predictors of adverse outcomes. Discussion There are more than 400,000 colposcopy appointments each year in England, of which 134,000 are new referrals. There is some evidence that there may be long-term implications for women treated under colposcopy with respect to adverse obstetric outcomes, persisting anxiety, increased rates of sexual dysfunction and reduced quality of life. Reliably establishing whether such adverse outcomes exist and the excess risk of adverse events will facilitate informed decision-making and patient choice.

  19. Geschlechterunterschiede beim kardialen Remodeling der extrazellulären Matrix durch Laufradtraining und Myokardinfarkt im Mausmodell

    OpenAIRE

    Ehrenberg, Nadine

    2010-01-01

    Cardiovascular diseases, especially the myocardial infarction, are the major cause of death in industrialized countries. Incidence and mortality show obvious gender-differences. Until menopause, women rarely have myocardial infarctions and mortality is also low. Postmeno-pausal however, the risk adapts quite fast and incidence and mortality rise. The reasons for the higher mortality in males are at least in the mouse model more fatal cardiac adaptations in extracellular matrix remodeling. Mal...

  20. Cutaneous lupus erythematosus and systemic lupus erythematosus are associated with clinically significant cardiovascular risk

    DEFF Research Database (Denmark)

    Hesselvig, J Halskou; Ahlehoff, O; Dreyer, L

    2017-01-01

    Systemic lupus erythematosus (SLE) is a well-known cardiovascular risk factor. Less is known about cutaneous lupus erythematosus (CLE) and the risk of developing cardiovascular disease (CVD). Therefore, we investigated the risk of mortality and adverse cardiovascular events in patients diagnosed...

  1. Laser therapy in cardiovascular disease

    Science.gov (United States)

    Rindge, David

    2009-02-01

    Cardiovascular disease is the number one cause of death worldwide. It is broadly defined to include anything which adversely affects the heart or blood vessels. One-third of Americans have one or more forms of it. By one estimate, average human life expectancy would increase by seven years if it were eliminated. The mainstream medical model seeks mostly to "manage" cardiovascular disease with pharmaceuticals or to surgically bypass or reopen blocked vessels via angioplasty. These methods have proven highly useful and saved countless lives. Yet drug therapy may be costly and ongoing, and it carries the risk of side effects while often doing little or nothing to improve underlying health concerns. Similarly, angioplasty or surgery are invasive methods which entail risk. Laser therapy1 regenerates tissue, stimulates biological function, reduces inflammation and alleviates pain. Its efficacy and safety have been increasingly well documented in cardiovascular disease of many kinds. In this article we will explore the effects of laser therapy in angina, atherosclerosis, coronary artery disease, hypertension, hyperlipidemia, myocardial infarction, stroke and other conditions. The clinical application of various methods of laser therapy, including laserpuncture and transcutaneous, supravascular and intravenous irradiation of blood will be discussed. Implementing laser therapy in the treatment of cardiovascular disease offers the possibility of increasing the health and wellbeing of patients while reducing the costs and enhancing safety of medical care.

  2. Adverse reactions to cosmetics

    Directory of Open Access Journals (Sweden)

    Dogra A

    2003-03-01

    Full Text Available Adverse reaction to cosmetics constitute a small but significant number of cases of contact dermatitis with varied appearances. These can present as contact allergic dermatitis, photodermatitis, contact irritant dermatitis, contact urticaria, hypopigmentation, hyperpigmentotion or depigmentation, hair and nail breakage. Fifty patients were included for the study to assess the role of commonly used cosmetics in causing adverse reactions. It was found that hair dyes, lipsticks and surprisingly shaving creams caused more reaction as compared to other cosmetics. Overall incidence of contact allergic dermatitis seen was 3.3% with patients own cosmetics. Patch testing was also done with the basic ingredients and showed positive results in few cases where casual link could be established. It is recommended that labeling of the cosmetics should be done to help the dermatologists and the patients to identify the causative allergen in cosmetic preparation.

  3. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

    Directory of Open Access Journals (Sweden)

    Thomas R. Cox

    2011-03-01

    Full Text Available Dynamic remodeling of the extracellular matrix (ECM is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

  4. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer.

    Science.gov (United States)

    Cox, Thomas R; Erler, Janine T

    2011-03-01

    Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM.

  5. Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer

    Science.gov (United States)

    Cox, Thomas R.; Erler, Janine T.

    2011-01-01

    Dynamic remodeling of the extracellular matrix (ECM) is essential for development, wound healing and normal organ homeostasis. Life-threatening pathological conditions arise when ECM remodeling becomes excessive or uncontrolled. In this Perspective, we focus on how ECM remodeling contributes to fibrotic diseases and cancer, which both present challenging obstacles with respect to clinical treatment, to illustrate the importance and complexity of cell-ECM interactions in the pathogenesis of these conditions. Fibrotic diseases, which include pulmonary fibrosis, systemic sclerosis, liver cirrhosis and cardiovascular disease, account for over 45% of deaths in the developed world. ECM remodeling is also crucial for tumor malignancy and metastatic progression, which ultimately cause over 90% of deaths from cancer. Here, we discuss current methodologies and models for understanding and quantifying the impact of environmental cues provided by the ECM on disease progression, and how improving our understanding of ECM remodeling in these pathological conditions is crucial for uncovering novel therapeutic targets and treatment strategies. This can only be achieved through the use of appropriate in vitro and in vivo models to mimic disease, and with technologies that enable accurate monitoring, imaging and quantification of the ECM. PMID:21324931

  6. Gender-related differences in β-adrenergic receptor-mediated cardiac remodeling.

    Science.gov (United States)

    Zhu, Baoling; Liu, Kai; Yang, Chengzhi; Qiao, Yuhui; Li, Zijian

    2016-12-01

    Cardiac remodeling is the pathological basis of various cardiovascular diseases. In this study, we found gender-related differences in β-adrenergic receptor (AR)-mediated pathological cardiac remodeling. Cardiac remodeling model was established by subcutaneous injection of isoprenaline (ISO) for 14 days. Heart rate (HR), mean arterial pressure (MAP), and echocardiography were obtained on 7th and 14th days during ISO administration. Myocardial cross-sectional area and the ratio of heart mass to tibia length (HM/TL) were detected to assess cardiac hypertrophy. Picro-Sirius red staining (picric acid + Sirius red F3B) was used to evaluate cardiac fibrosis. Myocardial capillary density was assessed by immunohistochemistry for von Willebrand factor. Further, real-time PCR was used to measure the expression of β1-AR and β2-AR. Results showed that ISO induced cardiac remodeling, the extent of which was different between female and male mice. The extent of increase in cardiac wall thickness, myocardial cross-sectional area, and collagen deposition in females was less than that in males. However, no gender-related difference was observed in HR, MAP, cardiac function, and myocardial capillary density. The distinctive decrease of β2-AR expression, rather than a decrease of β1-AR expression, seemed to result in gender-related differences in cardiac remodeling.

  7. The brain norepinephrine system, stress and cardiovascular vulnerability.

    Science.gov (United States)

    Wood, Susan K; Valentino, Rita J

    2017-03-01

    Chronic exposure to psychosocial stress has adverse effects on cardiovascular health, however the stress-sensitive neurocircuitry involved remains to be elucidated. The anatomical and physiological characteristics of the locus coeruleus (LC)-norepinephrine (NE) system position it to contribute to stress-induced cardiovascular disease. This review focuses on cardiovascular dysfunction produced by social stress and a major theme highlighted is that differences in coping strategy determine individual differences in social stress-induced cardiovascular vulnerability. The establishment of different coping strategies and cardiovascular vulnerability during repeated social stress has recently been shown to parallel a unique plasticity in LC afferent regulation, resulting in either excitatory or inhibitory input to the LC. This contrasting regulation of the LC would translate to differences in cardiovascular regulation and may serve as the basis for individual differences in the cardiopathological consequences of social stress. The advances described suggest new directions for developing treatments and/or strategies for decreasing stress-induced cardiovascular vulnerability.

  8. Insulin resistance and cardiovascular disease.

    Science.gov (United States)

    Egan, B M; Greene, E L; Goodfriend, T L

    2001-06-01

    Cardiovascular risk factors cluster in obese individuals. Insulin resistance emerges as a common pathogenetic denominator underlying the risk factor cluster. Defects in nonesterified fatty acids metabolism have been implicated in the abnormal lipid and glucose metabolism which characterize the cluster. Other evidence also leads to the adipocyte as an important contributor to the risk factor cluster and cardiovascular complications through effects not only on fatty acids but also on leptin, plasminogen activator inhibitor-1, and angiotensinogen, to name a few. Fatty acids are elevated among abdominally obese individuals, are more resistant to suppression by insulin, and may contribute to hypertension. Fatty acids may affect blood pressure by inhibiting endothelial nitric oxide synthase activity and impairing endothelium-dependent vasodilation. Fatty acids increase alpha1-adrenoceptor-mediated vascular reactivity and enhance the proliferation and migration of cultured vascular smooth-muscle cells. Several effects of fatty acids are mediated through oxidative stress. Fatty acids can also interact with other facets of cluster, including increased angiotensin II, to accentuate oxidative stress. Oxidative stress, in turn, is implicated in the pathogenesis of insulin resistance, hypertension, vascular remodeling, and vascular complications. A clearer delineation of the key reactive oxygen signaling pathways and the impact of various interventions on these pathways could facilitate a rationale approach to antioxidant therapy and improved outcomes among the rapidly growing number of high-risk, insulin-resistant, obese individuals.

  9. Matrix metalloproteinases as input and output signals for post-myocardial infarction remodeling.

    Science.gov (United States)

    Lindsey, Merry L; Iyer, Rugmani Padmanabhan; Jung, Mira; DeLeon-Pennell, Kristine Y; Ma, Yonggang

    2016-02-01

    Despite current optimal therapeutic regimens, approximately one in four patients diagnosed with myocardial infarction (MI) will go on to develop congestive heart failure, and heart failure has a high five-year mortality rate of 50%. Elucidating mechanisms whereby heart failure develops post-MI, therefore, is highly needed. Matrix metalloproteinases (MMPs) are key enzymes involved in post-MI remodeling of the left ventricle (LV). While MMPs process cytokine and extracellular matrix (ECM) substrates to regulate the inflammatory and fibrotic components of the wound healing response to MI, MMPs also serve as upstream signaling initiators with direct actions on cell signaling cascades. In this review, we summarize the current literature regarding MMP roles in post-MI LV remodeling. We also identify the current knowledge gaps and provide templates for experiments to fill these gaps. A more complete understanding of MMP roles, particularly with regards to upstream signaling roles, may provide new strategies to limit adverse LV remodeling.

  10. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes

    DEFF Research Database (Denmark)

    Marso, Steven P; Bain, Stephen C; Consoli, Agostino

    2016-01-01

    cardiovascular causes were similar in the two groups. Rates of new or worsening nephropathy were lower in the semaglutide group, but rates of retinopathy complications (vitreous hemorrhage, blindness, or conditions requiring treatment with an intravitreal agent or photocoagulation) were significantly higher...... (hazard ratio, 1.76; 95% CI, 1.11 to 2.78; P=0.02). Fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal. Conclusions In patients with type 2 diabetes who were at high cardiovascular risk, the rate......Background Regulatory guidance specifies the need to establish cardiovascular safety of new diabetes therapies in patients with type 2 diabetes in order to rule out excess cardiovascular risk. The cardiovascular effects of semaglutide, a glucagon-like peptide 1 analogue with an extended half...

  11. Remodeling, Renovation, & Conversion of Educational Facilities.

    Science.gov (United States)

    Association of Physical Plant Administrators of Universities and Colleges, Washington, DC.

    Based on a series of workshops, this collection of papers provides a framework for thought--emphasizing planning within time, flexibility, and maintenance constraints--as well as a practical guide for actual engineering of remodeling/renovation/conversion projects. Is remodeling always less expensive than new construction? Should high initial…

  12. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  13. Hypothyroidism and its rapid correction alter cardiac remodeling.

    Directory of Open Access Journals (Sweden)

    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.

  14. Endoglin: a critical mediator of cardiovascular health

    Directory of Open Access Journals (Sweden)

    Kapur NK

    2013-05-01

    Full Text Available Navin K Kapur,1 Kevin J Morine,1 Michelle Letarte2,31Molecular Cardiology Research Institute, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA; 2Molecular Structure and Function Program, Hospital for Sick Children, 3The Heart and Stroke Foundation Richard Lewar Centre of Excellence, and the Department of Immunology, University of Toronto, Toronto, Ontario, CanadaAbstract: Endoglin (CD105 is a type III auxiliary receptor for the transforming growth factor beta (TGFß superfamily. Several lines of evidence suggest that endoglin plays a critical role in maintaining cardiovascular homeostasis. Seemingly disparate disease conditions, including hereditary hemorrhagic telangiectasia, pre-eclampsia, and cardiac fibrosis, have now been associated with endoglin. Given the central role of the TGFß superfamily in multiple disease conditions, this review provides a detailed update on endoglin as an evolving therapeutic target in the management of cardiovascular disease.Keywords: endoglin, transforming growth factor beta, vascular, cardiac remodeling

  15. Vaccine adverse events.

    Science.gov (United States)

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  16. 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.

  17. 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.

  18. Sex steroids and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Bu Beng Yeap

    2014-04-01

    Full Text Available As men grow older, testosterone (T levels decline and the significance of this change is debated. The evidence supporting a causal role for lower circulating T, or its metabolites dihydrotestosterone (DHT and estradiol, in the genesis of atherosclerosis and cardiovascular disease (CVD in men is limited. Observational studies associate low baseline T levels with carotid atherosclerosis, aortic and peripheral vascular disease, and with the incidence of cardiovascular events and mortality. Studies using mass spectrometry suggest that when total T is assayed optimally, calculation of free T might not necessarily improve risk stratification. There is limited evidence to support an association of estradiol with CVD. Interventional studies of T therapy in men with coronary artery disease have shown beneficial effects on exercise-induced myocardial ischemia. However, placebo-controlled, randomized clinical trials (RCTs of T therapy in men with the prespecified outcomes of cardiovascular events or deaths are lacking. Meta-analyses of randomized controlled trials of T published up to 2010 found no increase in cardiovascular events, mortality, or prostate cancer with therapy. Recently, in a trial of older men with mobility limitations, men randomized to receive a substantial dose of T reported cardiovascular adverse effects. This phenomenon was not reported from a comparable trial where men received a more conservative dose of T, suggesting a prudent approach should be adopted when considering therapy in frail older men with existing CVD. Adequately powered RCTs of T in middle-aged and older men are needed to clarify whether or not hormonal intervention would reduce the incidence of CVD.

  19. Impact of gestational risk factors on maternal cardiovascular system

    Science.gov (United States)

    Perales, María; Santos-Lozano, Alejandro; Luaces, María; Pareja-Galeano, Helios; Garatachea, Nuria; Barakat, Rubén; Lucia, Alejandro

    2016-01-01

    Background Scarce evidence is available on the potential cardiovascular abnormalities associated with some common gestational complications. We aimed to analyze the potential maternal cardiac alterations related to gestational complications, including body mass index (BMI) >25 kg/m2, gaining excessive weight, or developing antenatal depression. Methods The design of this study was a secondary analysis of a randomized controlled trial. Echocardiography was performed to assess cardiovascular indicators of maternal hemodynamic, cardiac remodeling and left ventricular (LV) function in 59 sedentary pregnant women at 20 and 34 weeks of gestation. Results Starting pregnancy with a BMI >25 kg/m2, gaining excessive weight, and developing antenatal depression had no cardiovascular impact on maternal health (P value >0.002). Depressed women were more likely to exceed weight gain recommendations than non-depressed women (P value <0.002). Conclusions The evaluated gestational complications seem not to induce cardiovascular alterations in hemodynamic, remodeling and LV function indicators. However, developing antenatal depression increases the risk of an excessive weight gain. This finding is potentially important because excessive weight gain during pregnancy associates with a higher risk of cardiovascular diseases (CVD) later in life. PMID:27500154

  20. Airway remodeling in asthma: what really matters.

    Science.gov (United States)

    Fehrenbach, Heinz; Wagner, Christina; Wegmann, Michael

    2017-03-01

    Airway remodeling is generally quite broadly defined as any change in composition, distribution, thickness, mass or volume and/or number of structural components observed in the airway wall of patients relative to healthy individuals. However, two types of airway remodeling should be distinguished more clearly: (1) physiological airway remodeling, which encompasses structural changes that occur regularly during normal lung development and growth leading to a normal mature airway wall or as an acute and transient response to injury and/or inflammation, which ultimately results in restoration of a normal airway structures; and (2) pathological airway remodeling, which comprises those structural alterations that occur as a result of either disturbed lung development or as a response to chronic injury and/or inflammation leading to persistently altered airway wall structures and function. This review will address a few major aspects: (1) what are reliable quantitative approaches to assess airway remodeling? (2) Are there any indications supporting the notion that airway remodeling can occur as a primary event, i.e., before any inflammatory process was initiated? (3) What is known about airway remodeling being a secondary event to inflammation? And (4), what can we learn from the different animal models ranging from invertebrate to primate models in the study of airway remodeling? Future studies are required addressing particularly pheno-/endotype-specific aspects of airway remodeling using both endotype-specific animal models and "endotyped" human asthmatics. Hopefully, novel in vivo imaging techniques will be further advanced to allow monitoring development, growth and inflammation of the airways already at a very early stage in life.

  1. Maternal uterine vascular remodeling during pregnancy.

    Science.gov (United States)

    Osol, George; Mandala, Maurizio

    2009-02-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

  2. 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.

  3. Advances in chromatin remodeling and human disease.

    Science.gov (United States)

    Cho, Kyoung Sang; Elizondo, Leah I; Boerkoel, Cornelius F

    2004-06-01

    Epigenetic factors alter phenotype without changing genotype. A primary molecular mechanism underlying epigenetics is the alteration of chromatin structure by covalent DNA modifications, covalent histone modifications, and nucleosome reorganization. Remodeling of chromatin structure regulates DNA methylation, replication, recombination, and repair as well as gene expression. As these functions would predict, dysfunction of the proteins that remodel chromatin causes an array of multi-system disorders and neoplasias. Insights from these diseases suggest that during embryonic and fetal life, environmental distortions of chromatin remodeling encode a 'molecular memory' that predispose the individual to diseases in adulthood.

  4. Predictive value of heart fatty acid-binding protein to major adverse cardiovascular events in patients with acute myocardial infarction%心型脂肪酸结合蛋白对急性心肌梗死患者主要不良心脏事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    魏庆民; 周彬; 史永堂; 张友良

    2012-01-01

    Objective To observe the predictive value of peak concentration of plasma heart fatty acid-binding protein (H-FABP) to major adverse cardiovascular events ( MACE ) in patients with acute myocardial infarction ( AMI) . Methods The AMI patients ( n=60) were selected within two hours from admission to disease attack from Jan. 2010 to Jim. 2011. The concentration of plasma H-FABP was detected every two hours in the patients from admission to disease attack for 10 hours. According to the average value of H-FABP peak value, all the patients were divided into group A ( with higher H-FABP than average ) and group B ( with lower H-FABP than average ) . The occurrence status of MACE [severe heart failure, malignant arrhythmia, recurrent myocardial infarction, cardiac death and target lesion revascularization ( TLR ) ] was compared between two groups after disease attack for one month and one year. Results After disease attack for one month and one year, the incidence of severe heart failure was higher in group A than that in group B (P<0.05 ) , and the incidence of other events had no statistical difference between two groups. Conclusion The increase of H-FABP peak value has some predictive value to severe heart failure of MACE in AMI patients.%目的 观察血浆心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)的峰值浓度对急性心肌梗死(AMI)患者主要不良心脏事件(MACE)的预测价值.方法 入选2010年1月至2011年6月入院距发病时间2h以内的AMI患者60例,于入院即刻至发病10h期间,每2h测定1次血浆H-FABP的浓度.根据H-FABP峰值水平的平均值将患者划分为H-FABP高值组和低值组,比较两组患者发病后1个月、1年的主要不良心脏事件(严重心力衰竭、恶性心律失常、再发心肌梗死、心源性死亡、靶病变血管重建)的发生率.结果 与H-FABP低值组相比,H-FABP高值组发病后1个月、1年,MACE及严重心力衰竭的发生率更

  5. Air pollution and cardiovascular disease.

    Science.gov (United States)

    Nogueira, J Braz

    2009-06-01

    Air pollution is associated with increased cardiovascular morbidity and mortality. Recent experimental and epidemiologic studies show that particulate matter (PM) air pollution with PM10 or inhalable (thoracic) particles (mean aerodynamic diameter particles (aerodynamic diameter biological mechanisms responsible for adverse cardiovascular outcomes associated with PM have been described, including the release of pro-oxidative and pro-inflammatory mediators from the lungs into the circulation, autonomic nervous system imbalance, and the direct actions on the heart and vasculature of ultrafine particles translocated into the systemic circulation. The induction of oxidative stress by these particles may be central to all of these putative pathways that trigger coagulation and thrombosis, increased heart rate and reduced heart rate variability, endothelial dysfunction, arterial vasoconstriction, apoptosis, and hypertension. In chronic exposures these alterations favor the development and progression of atherosclerosis and possibly of hypertension in the long term, and in the short term acute exposures contribute to plaque instability, affect various traditional risk factors and trigger acute cardiovascular events (myocardial ischemia and infarction, stroke, heart failure, arrhythmias, and sudden death), particularly in high-risk subjects. There are currently also significant concerns with the risks of engineered nanoparticles.

  6. Simulations of trabecular remodeling and fatigue: is remodeling helpful or harmful?

    Science.gov (United States)

    van Oers, René F M; van Rietbergen, Bert; Ito, Keita; Huiskes, Rik; Hilbers, Peter A J

    2011-05-01

    Microdamage-targeted resorption is paradoxal, because it entails the removal of bone from a region that was already overloaded. Under continued intense loading, resorption spaces could potentially cause more damage than they remove. To investigate this problem, we incorporated damage algorithms in a computer-simulation model for trabecular remodeling. We simulated damage accumulation and bone remodeling in a trabecular architecture, for two fatigue regimens, a 'moderate' regimen, and an 'intense' regimen with a higher number of loading cycles per day. Both simulations were also performed without bone remodeling to investigate if remodeling removed or exacerbated the damage. We found that remodeling tends to remove damage under the 'moderate' fatigue regimen, but it exacerbates damage under the 'intense' regimen. This harmful effect of remodeling may play a role in the development of stress fractures.

  7. Level of matrix metalloproteinase-9 and myocardium remodeling in patients with acute postinfarction aneurism of left ventricle

    Directory of Open Access Journals (Sweden)

    V. D. Syvolap

    2013-12-01

    Full Text Available 67 patients with diagnosis: Q-wave myocardial infarction – were examined. Level of matrix metalloproteinase-9, structural and functional indexes of myocardium remodeling were studied in patients with acute postinfarction aneurism of left ventricle. Early predictors of left ventricle aneurism formation were revealed in patients with acute Q-wave myocardial infarction. Abstract Background. Problem of acute myocardial infarction till nowadays remains relevant, because it’s one of the leading causes of mortality, morbidity and disability in most developed countries. Severity of postinfarction remodeling is a factor that determines the degree of myocardial dysfunction and prognosis of survival. During the first few days after the onset of AMI disproportionately thinned and stretched infarcted area, which is no longer able to resist to intraventricular pressure, which subsequently leads to an expansion of a heart attack until the formation of an aneurysm or heart failure. In this case, the structural and functional changes in the heart muscle affects both the affected and intact areas of the myocardium , marked by the passage of the phase of adaptive and maladaptive processes. Mechanisms of postinfarction remodeling caused by the interaction of cell as well as extracellular factors, starting immediately after coronary artery occlusion with the normal degradation of the extracellular matrix , migration of inflammatory cells to the site of damage and induction of biologically active peptides. In recent studies there was a high expression of MMP -9 in patients with acute coronary syndrome, showing the value of its serum concentration as a marker of inflammation, a predictor of restenosis and cardiovascular mortality in patients with coronary heart disease. This gives reason to explore the prognostic value of early detection of the level of MMP -9 in myocardial infarction as a marker of adverse postinfarction remodeling. Methods. Sixty seven patients

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Cardiovascular Disease and Diabetes

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Nov 4,2016 The following statistics speak ... disease. This content was last reviewed August 2015. Diabetes • Home • About Diabetes • Why Diabetes Matters Introduction Cardiovascular ...

  10. Cardiovascular manifestations of phaeochromocytoma

    NARCIS (Netherlands)

    Prejbisz, A.; Lenders, J.W.M.; Eisenhofer, G.; Januszewicz, A.

    2011-01-01

    Clinical expression of phaeochromocytoma may involve numerous cardiovascular manifestations, but usually presents as sustained or paroxysmal hypertension associated with other signs and symptoms of catecholamine excess. Most of the life-threatening cardiovascular manifestations of phaeochromocytoma,

  11. Understanding cardiovascular disease

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000759.htm Understanding cardiovascular disease To use the sharing features on this page, ... lead to heart attack or stroke. Types of Cardiovascular Disease Coronary heart disease (CHD) is the most common ...

  12. APOE Genotyping, Cardiovascular Disease

    Science.gov (United States)

    ... Home Visit Global Sites Search Help? APOE Genotyping, Cardiovascular Disease Share this page: Was this page helpful? Also ... of choice to decrease the risk of developing cardiovascular disease (CVD) . However, there is a wide variability in ...

  13. Space radiation and cardiovascular disease risk

    Institute of Scientific and Technical Information of China (English)

    Marjan Boerma; Gregory A Nelson; Vijayalakshmi Sridharan; Xiao-Wen Mao; Igor Koturbash; Martin Hauer-Jensen

    2015-01-01

    Future long-distance space missions will be associated with significant exposures to ionizing radiation,and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Groundbased studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses,appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk,and several other studies are ongoing. Moreover,astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation,and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined,the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.

  14. Space radiation and cardiovascular disease risk.

    Science.gov (United States)

    Boerma, Marjan; Nelson, Gregory A; Sridharan, Vijayalakshmi; Mao, Xiao-Wen; Koturbash, Igor; Hauer-Jensen, Martin

    2015-12-26

    Future long-distance space missions will be associated with significant exposures to ionizing radiation, and the health risks of these radiation exposures during manned missions need to be assessed. Recent Earth-based epidemiological studies in survivors of atomic bombs and after occupational and medical low dose radiation exposures have indicated that the cardiovascular system may be more sensitive to ionizing radiation than was previously thought. This has raised the concern of a cardiovascular disease risk from exposure to space radiation during long-distance space travel. Ground-based studies with animal and cell culture models play an important role in estimating health risks from space radiation exposure. Charged particle space radiation has dense ionization characteristics and may induce unique biological responses, appropriate simulation of the space radiation environment and careful consideration of the choice of the experimental model are critical. Recent studies have addressed cardiovascular effects of space radiation using such models and provided first results that aid in estimating cardiovascular disease risk, and several other studies are ongoing. Moreover, astronauts could potentially be administered pharmacological countermeasures against adverse effects of space radiation, and research is focused on the development of such compounds. Because the cardiovascular response to space radiation has not yet been clearly defined, the identification of potential pharmacological countermeasures against cardiovascular effects is still in its infancy.

  15. Raise the Floor When Remodeling Science Labs

    Science.gov (United States)

    Nation's Schools, 1972

    1972-01-01

    A new remodeling idea adopts the concept of raised floor covering gas, water, electrical, and drain lines. The accessible floor has removable panels set into an adjustable support frame 24 inches above a concrete subfloor. (Author)

  16. Cholinergic regulation of airway inflammation and remodelling

    NARCIS (Netherlands)

    Kolahian, Saeed; Gosens, Reinoud

    2012-01-01

    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 disease

  17. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications...

  18. The Adverse Effects of Air Pollution on the Nervous System

    OpenAIRE

    Sermin Genc; Zeynep Zadeoglulari; Fuss, Stefan H.; Kursad Genc

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer’s disease, Parkinson’s dise...

  19. Chromatin Modification and Remodeling in Heart Development

    Directory of Open Access Journals (Sweden)

    Paul Delgado-Olguín

    2006-01-01

    Full Text Available In organogenesis, cell types are specified from determined precursors as morphogenetic patterning takes place. These events are largely controlled by tissue-specific transcription factors. These transcription factors must function within the context of chromatin to activate or repress target genes. Recent evidence suggests that chromatin-remodeling and -modifying factors may have tissue-specific function. Here we review the potential roles for chromatin-remodeling and -modifying proteins in the development of the mammalian heart.

  20. The Chd Family of Chromatin Remodelers

    OpenAIRE

    Marfella, Concetta G.A.; Imbalzano, Anthony N.

    2007-01-01

    Chromatin remodeling enzymes contribute to the dynamic changes that occur in chromatin structure during cellular processes such as transcription, recombination, repair, and replication. Members of the chromodomain helicase DNA-binding (Chd) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The Chd proteins are distinguished by the presence of two N-terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic,...

  1. 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.

  2. 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.

  3. Cardiovascular comorbiditiy in psoriasis

    OpenAIRE

    Gurcharan Singh; Simran Pal Singh Aneja

    2011-01-01

    The chronic inflammatory nature of psoriasis is also thought to predispose patients to other diseases with an inflammatory component, the most notable being cardiovascular and metabolic (cardiometabolite) disorders. This concept is supported by studies showing that psoriasis is associated with cardiovascular risk factors like diabetes, obesity, hypertension, dyslipidemia, smoking and diseases including MI. Given the increased prevalence of cardiovascular co morbidities in patients, dermatolog...

  4. 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.

  5. Bone remodeling as a spatial evolutionary game.

    Science.gov (United States)

    Ryser, Marc D; Murgas, Kevin A

    2017-04-07

    Bone remodeling is a complex process involving cell-cell interactions, biochemical signaling and mechanical stimuli. Early models of the biological aspects of remodeling were non-spatial and focused on the local dynamics at a fixed location in the bone. Several spatial extensions of these models have been proposed, but they generally suffer from two limitations: first, they are not amenable to analysis and are computationally expensive, and second, they neglect the role played by bone-embedded osteocytes. To address these issues, we developed a novel model of spatial remodeling based on the principles of evolutionary game theory. The analytically tractable framework describes the spatial interactions between zones of bone resorption, bone formation and quiescent bone, and explicitly accounts for regulation of remodeling by bone-embedded, mechanotransducing osteocytes. Using tools from the theory of interacting particle systems we systematically classified the different dynamic regimes of the spatial model and identified regions of parameter space that allow for global coexistence of resorption, formation and quiescence, as observed in physiological remodeling. In coexistence scenarios, three-dimensional simulations revealed the emergence of sponge-like bone clusters. Comparison between spatial and non-spatial dynamics revealed substantial differences and suggested a stabilizing role of space. Our findings emphasize the importance of accounting for spatial structure and bone-embedded osteocytes when modeling the process of bone remodeling. Thanks to the lattice-based framework, the proposed model can easily be coupled to a mechanical model of bone loading.

  6. 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...

  7. 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...

  8. Right ventricular relative wall thickness as a predictor of outcomes and of right ventricular reverse remodeling for patients with pulmonary hypertension.

    Science.gov (United States)

    Sano, Hiroyuki; Tanaka, Hidekazu; Motoji, Yoshiki; Fukuda, Yuko; Mochizuki, Yasuhide; Hatani, Yutaka; Matsuzoe, Hiroki; Hatazawa, Keiko; Shimoura, Hiroyuki; Ooka, Junichi; Ryo-Koriyama, Keiko; Nakayama, Kazuhiko; Matsumoto, Kensuke; Emoto, Noriaki; Hirata, Ken-Ichi

    2017-03-01

    Mid-term right ventricular (RV) reverse remodeling after treatment in patients with pulmonary hypertension (PH) is associated with long-term outcome as well as baseline RV remodeling. However, baseline factors influencing mid-term RV reverse remodeling after treatment and its prognostic capability remain unclear. We studied 54 PH patients. Mid-term RV remodeling was assessed in terms of the RV area, which was traced planimetrically at the end-systole (RVESA). RV reverse remodeling was defined as a relative decrease in the RVESA of at least 15% at 10.2 ± 9.4 months after treatment. Long-term follow-up was 5 years. Adverse events occurred in ten patients (19%) and mid-term RV reverse remodeling after treatment was observed in 37 (69%). Patients with mid-term RV reverse remodeling had more favorable long-term outcomes than those without (log-rank: p = 0.01). Multivariate logistic regression analysis showed that RV relative wall thickness (RV-RWT), as calculated as RV free-wall thickness/RV basal linear dimension at end-diastole, was an independent predictor of mid-term RV reverse remodeling (OR 1.334; 95% CI, 1.039-1.713; p = 0.03). Moreover, patients with RV-RWT ≥0.21 showed better long-term outcomes than did those without (log-rank p = 0.03), while those with RV-RWT ≥0.21 and mid-term RV reverse remodeling had the best long-term outcomes. Patients with RV-RWT remodeling, on the other hand, had worse long-term outcomes than other sub-groups. In conclusions, RV-RWT could predict mid-term RV reverse remodeling after treatment in PH patients, and was associated with long-term outcomes. Our finding may have clinical implications for better management of PH patients.

  9. Future of Pharmacogenetics in Cardiovascular Diseases

    OpenAIRE

    Schie, Rianne; Verhoef, Talitha; Maitland-van der Zee, Anke-Hilse; de Boer, Anthonius; van der Meer, F.J.M.; Redekop, Ken; Thariani, Rahber

    2012-01-01

    textabstractIntroduction: Pharmacogenetics is the study of variations in DNA sequence as related to drug response (European Medicines Agency [EMA], 2007). Several gene-drug interactions have been discovered in the field of cardiovascular diseases (CVDs). These gene-drug interactions can help to identify nonresponse to drugs, estimate dose requirements or identify an increased risk of developing adverse drug reactions. An individualized approach based on pharmacogenetic testing will provide ph...

  10. Cardiovascular events in patients with COPD: TORCH study results

    DEFF Research Database (Denmark)

    Calverley, Peter M A; Anderson, Julie A; Celli, Bartolome;

    2010-01-01

    BACKGROUND: Previous studies have suggested that long-term use of beta agonists to treat chronic obstructive pulmonary disease (COPD) may increase the risk of cardiovascular adverse events. In this post hoc analysis, data from the TOwards a Revolution in COPD Health (TORCH) study were used...... to investigate whether use of the long-acting beta(2) agonist salmeterol over 3 years increased the risk of cardiovascular adverse events in patients with moderate to severe COPD. METHODS: TORCH was a randomised, double-blind, placebo controlled study conducted at 444 centres in 42 countries. Patients (n=6184.......2% for placebo, 22.7% for salmeterol, 24.3% for fluticasone propionate and 20.8% for SFC. Although a history of myocardial infarction doubled the probability of cardiovascular adverse events, the event rates remained similar across treatment groups. CONCLUSION: Post hoc analysis of the 3-year TORCH dataset...

  11. Testosterone Replacement Therapy and the Cardiovascular System.

    Science.gov (United States)

    Naderi, Sahar

    2016-04-01

    As testosterone replacement therapy (TRT) has emerged as a commonly prescribed therapy for symptomatic low testosterone, conflicting data have been reported in terms of both its efficacy and potential adverse outcomes. One of the most controversial associations has been that of TRT and cardiovascular morbidity and mortality. This review briefly provides background on the history of TRT, the indications for TRT, and the data behind TRT for symptomatic low testosterone. It then specifically delves into the rather limited data for cardiovascular outcomes of those with low endogenous testosterone and those who receive TRT. The available body of literature strongly suggests that more work, by way of clinical trials, needs to be done to better understand the impact of testosterone and TRT on the cardiovascular system.

  12. ISPD Cardiovascular and Metabolic Guidelines in Adult Peritoneal Dialysis Patients Part I - Assessment and Management of Various Cardiovascular Risk Factors.

    Science.gov (United States)

    Wang, Angela Yee Moon; Brimble, K Scott; Brunier, Gillian; Holt, Stephen G; Jha, Vivekanand; Johnson, David W; Kang, Shin-Wook; Kooman, Jeroen P; Lambie, Mark; McIntyre, Chris; Mehrotra, Rajnish; Pecoits-Filho, Roberto

    2015-01-01

    Cardiovascular disease contributes significantly to the adverse clinical outcomes of peritoneal dialysis (PD) patients. Numerous cardiovascular risk factors play important roles in the development of various cardiovascular complications. Of these, loss of residual renal function is regarded as one of the key cardiovascular risk factors and is associated with an increased mortality and cardiovascular death. It is also recognized that PD solutions may incur significant adverse metabolic effects in PD patients. The International Society for Peritoneal Dialysis (ISPD) commissioned a global workgroup in 2012 to formulate a series of recommendations regarding lifestyle modification, assessment and management of various cardiovascular risk factors, as well as management of the various cardiovascular complications including coronary artery disease, heart failure, arrhythmia (specifically atrial fibrillation), cerebrovascular disease, peripheral arterial disease and sudden cardiac death, to be published in 2 guideline documents. This publication forms the first part of the guideline documents and includes recommendations on assessment and management of various cardiovascular risk factors. The documents are intended to serve as a global clinical practice guideline for clinicians who look after PD patients. The ISPD workgroup also identifies areas where evidence is lacking and further research is needed.

  13. Ranking Adverse Drug Reactions With Crowdsourcing

    KAUST Repository

    Gottlieb, Assaf

    2015-03-23

    Background: There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective: The intent of the study was to rank ADRs according to severity. Methods: We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results: There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions: ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making.

  14. Sleep Deficiency and Deprivation Leading to Cardiovascular Disease

    OpenAIRE

    Michelle Kohansieh; Amgad N. Makaryus

    2015-01-01

    Sleep plays a vital role in an individual’s mental, emotional, and physiological well-being. Not only does sleep deficiency lead to neurological and psychological disorders, but also the literature has explored the adverse effects of sleep deficiency on the cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD) risk factors, such as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep de...

  15. Reverse right ventricular structural and extracellular matrix remodeling by estrogen in severe pulmonary hypertension.

    Science.gov (United States)

    Nadadur, Rangarajan D; Umar, Soban; Wong, Gabriel; Eghbali, Mansour; Iorga, Andrea; Matori, Humann; Partow-Navid, Rod; Eghbali, Mansoureh

    2012-07-01

    Chronic pulmonary hypertension (PH) leads to right-ventricular failure (RVF) characterized by RV remodeling. Ventricular remodeling is emerging as an important process during heart failure and recovery. Remodeling in RVF induced by PH is not fully understood. Recently we discovered that estrogen (E2) therapy can rescue severe preexisting PH. Here, we focused on whether E2 (42.5 μg·kg(-1)·day(-1), 10 days) can reverse adverse RV structural and extracellular matrix (ECM) remodeling induced by PH using monocrotaline (MCT, 60 mg/kg). RV fibrosis was evident in RVF males. Intact females developed less severe RV remodeling compared with males and ovariectomized (OVX) females. Novel ECM-degrading disintegrin-metalloproteinases ADAM15 and ADAM17 transcripts were elevated ∼2-fold in all RVF animals. E2 therapy reversed RV remodeling in all groups. In vitro, E2 directly inhibited ANG II-induced expression of fibrosis markers as well as the metalloproteinases in cultured cardiac fibroblasts. Estrogen receptor-β agonist diarylpropionitrile (DPN) but not estrogen receptor-α agonist 4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT) was as effective as E2 in inhibiting expression of these genes. Expression of ECM-interacting cardiac fetal-gene osteopontin (OPN) also increased ∼9-fold in RVF males. Intact females were partially protected from OPN upregulation (∼2-fold) but OVX females were not. E2 reversed OPN upregulation in all groups. Upregulation of OPN was also reversed in vitro by E2. Plasma OPN was elevated in RVF (∼1.5-fold) and decreased to control levels in the E2 group. RVF resulted in elevated Akt phosphorylation, but not ERK, in the RV, and E2 therapy restored Akt phosphorylation. In conclusion, E2 therapy reverses adverse RV remodeling associated with PH by reversing fibrosis and upregulation of novel ECM enzymes ADAM15, ADAM17, and OPN. These effects are likely mediated through estrogen receptor-β.

  16. Adverse Reactions to Hallucinogenic Drugs.

    Science.gov (United States)

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  17. Circulating microRNAs in Cardiovascular Diseases.

    Science.gov (United States)

    Orlicka-Płocka, Marta; Gurda, Dorota; Fedoruk-Wyszomirska, Agnieszka; Smolarek, Iwona; Wyszko, Eliza

    2016-01-01

    Cardiovascular Diseases (CD) are currently one of the most common causes of death. Because heart related deaths occur on such an enormous scale this phenomenon is referred to as an epidemic. Chronic and acute injury of the heart could be an effect of cardiac remodeling, which is a result of molecular, cellular and interstitial changes, influenced by hemodynamic load or neurohormonal activation (Cohn et al., 2000). These small deviations in cardiac activity and morphology may lead to an enormous negative effect. Despite a significant progress, knowledge of standard risk factors for cardiovascular diseases has become less and less effective, which is why predicting and seeking an appropriate treatment is very challenging. As a result, there is a growing interest in finding new markers of the CD. MicroRNAs (miRNAs), are short, non-coding RNAs responsible for regulation of gene expression at the post-transcriptional level. Among them that have the greatest potential are microRNA molecules that circulate in the blood plasma or serum, that are related to direct activation of signaling pathways, implicated in the aging process and thus for the development of cardiovascular disease. This paper is a summary of the current state of knowledge on miRNAs, their biogenesis and potential role as biomarkers to diagnose heart disease.

  18. Sleep Deficiency and Deprivation Leading to Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Michelle Kohansieh

    2015-01-01

    Full Text Available Sleep plays a vital role in an individual’s mental, emotional, and physiological well-being. Not only does sleep deficiency lead to neurological and psychological disorders, but also the literature has explored the adverse effects of sleep deficiency on the cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD risk factors, such as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep deficiency and deprivation as a cause for cardiovascular disease and cite endothelial dysfunction as a common underlying mechanism.

  19. Adult ADHD Medications and Their Cardiovascular Implications

    Directory of Open Access Journals (Sweden)

    A. Sinha

    2016-01-01

    Full Text Available Attention-deficit/hyperactivity disorder (ADHD is a chronic neurobiological disorder exhibited by difficulty maintaining attention, as well as hyperactivity and impulsive behavior. Central nervous system (CNS stimulants are the first line of treatment for ADHD. With the increase in number of adults on CNS stimulants, the question that arises is how well do we understand the long-term cardiovascular effects of these drugs. There has been increasing concern that adults with ADHD are at greater risk for developing adverse cardiovascular events such as sudden death, myocardial infarction, and stroke as compared to pediatric population. Cardiovascular response attributed to ADHD medication has mainly been observed in heart rate and blood pressure elevations, while less is known about the etiology of rare cardiovascular events like acute myocardial infarction (AMI, arrhythmia, and cardiomyopathy and its long-term sequelae. We present a unique case of AMI in an adult taking Adderall (mixed amphetamine salts and briefly discuss the literature relevant to the cardiovascular safety of CNS stimulants for adult ADHD.

  20. Astaxanthin in cardiovascular health and disease.

    Science.gov (United States)

    Fassett, Robert G; Coombes, Jeff S

    2012-02-20

    Oxidative stress and inflammation are established processes contributing to cardiovascular disease caused by atherosclerosis. However, antioxidant therapies tested in cardiovascular disease such as vitamin E, C and β-carotene have proved unsuccessful at reducing cardiovascular events and mortality. Although these outcomes may reflect limitations in trial design, new, more potent antioxidant therapies are being pursued. Astaxanthin, a carotenoid found in microalgae, fungi, complex plants, seafood, flamingos and quail is one such agent. It has antioxidant and anti-inflammatory effects. Limited, short duration and small sample size studies have assessed the effects of astaxanthin on oxidative stress and inflammation biomarkers and have investigated bioavailability and safety. So far no significant adverse events have been observed and biomarkers of oxidative stress and inflammation are attenuated with astaxanthin supplementation. Experimental investigations in a range of species using a cardiac ischaemia-reperfusion model demonstrated cardiac muscle preservation when astaxanthin is administered either orally or intravenously prior to the induction of ischaemia. Human clinical cardiovascular studies using astaxanthin therapy have not yet been reported. On the basis of the promising results of experimental cardiovascular studies and the physicochemical and antioxidant properties and safety profile of astaxanthin, clinical trials should be undertaken.

  1. Prevention of cardiovascular disease in women.

    Science.gov (United States)

    Bavry, Anthony A; Limacher, Marian C

    2014-11-01

    Cardiovascular disease is the leading cause of death among women. In fact, the cardiovascular disease mortality rate among women exceeds the rate in men. Unfortunately, many minority women are still unaware of the importance of this disease. All women, including those with no history of cardiovascular disease, should have an accurate estimate of the probability of a cardiovascular disease event (death, myocardial infarction, or stroke) usually within the next decade. Such an estimate will help determine if women are candidates for preventive measures and specific therapies such as aspirin. Data from the Framingham Heart Study were used to construct a risk score, which is now widely used; however, other risk scores are available. To prevent cardiovascular disease, women should refrain from smoking, maintain a healthy weight, eat a heart-healthy diet, be physically active, and have normal blood pressure and cholesterol levels. Aspirin can be considered for primary prevention, with expected benefit to prevent ischemic stroke; however, this needs to be balanced against potential bleeding risk. Hormone therapy is no longer recommended due to an increase in adverse events (most consistently seen as increased ischemic stroke risk). Folic acid is also no longer recommended due to lack of benefit.

  2. Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation - Potential implications for cyclooxygenase-2 inhibition

    NARCIS (Netherlands)

    Arehart, Eric; Stitham, Jeremiah; Asselbergs, Folkert W.; Douville, Karen; MacKenzie, Todd; Fetalvero, Kristina M.; Gleim, Scott; Kasza, Zsolt; Rao, Yamini; Martel, Laurie; Segel, Sharon; Robb, John; Kaplan, Aaron; Simons, Michael; Powell, Richard J.; Moore, Jason H.; Rimm, Eric B.; Martin, Kathleen A.; Hwa, John

    2008-01-01

    Recent increased adverse cardiovascular events observed with selective cyclooxygenase-2 inhibition led to the withdrawal of rofecoxib ( Vioxx) and valdecoxib ( Bextra), but the mechanisms underlying these atherothrombotic events remain unclear. Prostacyclin is the major end product of cyclooxygenase

  3. Molecular Aspects of Exercise-induced Cardiac Remodeling.

    Science.gov (United States)

    Bernardo, Bianca C; McMullen, Julie R

    2016-11-01

    Exercise-induced cardiac remodeling is typically an adaptive response associated with cardiac myocyte hypertrophy and renewal, increased cardiac myocyte contractility, sarcomeric remodeling, cell survival, metabolic and mitochondrial adaptations, electrical remodeling, and angiogenesis. Initiating stimuli/triggers of cardiac remodeling include increased hemodynamic load, increased sympathetic activity, and the release of hormones and growth factors. Prolonged and strenuous exercise may lead to maladaptive exercise-induced cardiac remodeling including cardiac dysfunction and arrhythmia. In addition, this article describes novel therapeutic approaches for the treatment of heart failure that target mechanisms responsible for adaptive exercise-induced cardiac remodeling, which are being developed and tested in preclinical models.

  4. Updates on cardiovascular comorbidities associated with psoriatic diseases: epidemiology and mechanisms.

    Science.gov (United States)

    Yim, Kaitlyn M; Armstrong, April W

    2017-01-01

    Psoriasis and psoriatic arthritis are associated with a significantly increased risk of cardiovascular risk factors and major adverse cardiovascular events (MACE). Active research is ongoing to elucidate this relationship between psoriatic diseases and cardiovascular comorbidities, as well as their shared pathogenic mechanisms. This review focuses on (1) the epidemiologic association between psoriasis and cardiovascular risk factors, (2) the epidemiologic association between psoriasis and MACE, (3) the epidemiologic association between psoriatic arthritis, cardiovascular risk factors, and MACE, and (4) proposed mechanisms for the contribution of psoriatic diseases to cardiovascular diseases. The proposed mechanisms for shared pathogenesis between psoriatic diseases and cardiovascular diseases are inflammation, insulin resistance, dyslipidemia, angiogenesis, oxidative stress, and endothelial dysfunction. There is complex interplay and overlap among these mechanisms and their contributions to shared pathogenesis. Future translational research is necessary to elucidate the link between psoriatic diseases and cardiovascular diseases. Such findings may be applied clinically to improve the lives of psoriasis patients.

  5. Influenza vaccines for preventing cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Christine Clar

    Full Text Available ABSTRACTBACKGROUND: This is an update of the original review published in 2008. The risk of adverse cardiovascular outcomes is increased with influenza-like infection, and vaccination against influenza may improve cardiovascular outcomes.OBJECTIVES: To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease.METHODS:Search methods:We searched the following electronic databases on 18 October 2013: The Cochrane Library (including Cochrane Central Register of Controlled Trials (CENTRAL, Database of Abstracts of Reviews of Effects (DARE, Economic Evaluation Database (EED and Health Technology Assessment database (HTA, MEDLINE, EMBASE, Science Citation Index Expanded, Conference Proceedings Citation Index - Science and ongoing trials registers (www.controlled-trials.com/ and www.clinicaltrials.gov. We examined reference lists of relevant primary studies and systematic reviews. We performed a limited PubMed search on 20 February 2015, just before publication.Selection criteria:Randomised controlled trials (RCTs of influenza vaccination compared with placebo or no treatment in participants with or without cardiovascular disease, assessing cardiovascular death or non-fatal cardiovascular events.Data collection and analysis:We used standard methodological procedures as expected by The Cochrane Collaboration. We carried out meta-analyses only for cardiovascular death, as other outcomes were reported too infrequently. We expressed effect sizes as risk ratios (RRs, and we used random-effects models.MAIN RESULTS: We included eight trials of influenza vaccination compared with placebo or no vaccination, with 12,029 participants receiving at least one vaccination or control treatment. We included six new studies (n = 11,251, in addition to the two included in the previous version of the review. Four of these trials (n = 10,347 focused on prevention of influenza in the general or elderly population

  6. Adverse Event Reporting System (AERS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Adverse Event Reporting System (AERS) is a computerized information database designed to support the FDA's post-marketing safety surveillance program for all...

  7. Impact of urate level on cardiovascular risk in allopurinol treated patients. A nested case control study

    DEFF Research Database (Denmark)

    Larsen, Kasper Søltoft; Pottegård, Anton; Lindegaard, H. M.;

    2015-01-01

    Background: Gout gives rise to increased risk of adverse cardiovascular outcomes. Gout attacks can be effectively prevented with urate lowering drugs such as allopurinol, and allopurinol further potentially reduces the cardiovascular risk. Whether treatment to a target level of uric acid...

  8. Strategies for Energy Efficient Remodeling: SEER 2003 Case Study Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2004-11-01

    The goal of the Strategies for Energy Efficiency in Remodeling (SEER) project is to provide information, based on research and case studies, to remodelers and consumers about opportunities to increase home energy performance.

  9. Chinese Herbal Medicine on Cardiovascular Diseases and the Mechanisms of Action

    OpenAIRE

    Cuiqing Liu; Yu Huang

    2016-01-01

    Cardiovascular diseases are the principal cause of death worldwide. The potentially serious adverse effects of therapeutic drugs lead to growing awareness of the role of Chinese herbal medicine in the treatment of cardiovascular diseases. Chinese herbal medicine has been widely used in many countries especially in China from antiquity, however, the mechanisms by which herbal medicine acts in the prevention and treatment of cardiovascular diseases are far from clear. In this review, we briefly...

  10. Dietary sodium and cardiovascular disease.

    Science.gov (United States)

    Smyth, Andrew; O'Donnell, Martin; Mente, Andrew; Yusuf, Salim

    2015-06-01

    Although an essential nutrient, higher sodium intake is associated with increasing blood pressure (BP), forming the basis for current population-wide sodium restriction guidelines. While short-term clinical trials have achieved low intake (6 months). Guidelines assume that low sodium intake will reduce BP and reduce cardiovascular disease (CVD), compared to moderate intake. However, current observational evidence suggests a J-shaped association between sodium intake and CVD; the lowest risks observed with 3-5 g/day but higher risk with 5 g/day) and increased risk of CVD. Although lower intake may reduce BP, this may be offset by marked increases in neurohormones and other adverse effects which may paradoxically be adverse. Large randomised clinical trials with sufficient follow-up are required to provide robust data on the long-term effects of sodium reduction on CVD incidence. Until such trials are completed, current evidence suggests that moderate sodium intake for the general population (3-5 g/day) is likely the optimum range for CVD prevention.

  11. 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.

  12. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction.

    Science.gov (United States)

    Wang, Wei; Zhang, Fuyang; Xia, Yunlong; Zhao, Shihao; Yan, Wenjun; Wang, Helin; Lee, Yan; Li, Congye; Zhang, Ling; Lian, Kun; Gao, Erhe; Cheng, Hexiang; Tao, Ling

    2016-11-01

    Cardiac metabolic remodeling is a central event during heart failure (HF) development following myocardial infarction (MI). It is well known that myocardial glucose and fatty acid dysmetabolism contribute to post-MI cardiac dysfunction and remodeling. However, the role of amino acid metabolism in post-MI HF remains elusive. Branched chain amino acids (BCAAs) are an important group of essential amino acids and function as crucial nutrient signaling in mammalian animals. The present study aimed to determine the role of cardiac BCAA metabolism in post-MI HF progression. Utilizing coronary artery ligation-induced murine MI models, we found that myocardial BCAA catabolism was significantly impaired in response to permanent MI, therefore leading to an obvious elevation of myocardial BCAA abundance. In MI-operated mice, oral BCAA administration further increased cardiac BCAA levels, activated the mammalian target of rapamycin (mTOR) signaling, and exacerbated cardiac dysfunction and remodeling. These data demonstrate that BCAAs act as a direct contributor to post-MI cardiac pathologies. Furthermore, these BCAA-mediated deleterious effects were improved by rapamycin cotreatment, revealing an indispensable role of mTOR in BCAA-mediated adverse effects on cardiac function/structure post-MI. Of note, pharmacological inhibition of branched chain ketoacid dehydrogenase kinase (BDK), a negative regulator of myocardial BCAA catabolism, significantly improved cardiac BCAA catabolic disorders, reduced myocardial BCAA levels, and ameliorated post-MI cardiac dysfunction and remodeling. In conclusion, our data provide the evidence that impaired cardiac BCAA catabolism directly contributes to post-MI cardiac dysfunction and remodeling. Moreover, improving cardiac BCAA catabolic defects may be a promising therapeutic strategy against post-MI HF.

  13. Lifestyle in Cardiovascular Disease

    NARCIS (Netherlands)

    J.O. Younge (John)

    2015-01-01

    markdownabstract__Abstract__ Globally, the burden of cardiovascular disease (CVD) is still increasing. However, in recent decades, better treatment modalities have led to less cardiovascular related deaths. After years of research, we now generally accept that lifestyle factors are the most importa

  14. Over-expression of Arabidopsis AtCHR23 chromatin remodeling ATPase results in increased variability of growth and gene expression

    NARCIS (Netherlands)

    Folta, A.; Severing, E.I.; Krauskopf, J.; Geest, van de H.C.; Verver, J.; Nap, J.P.H.; Mlynarova, L.

    2014-01-01

    Background Plants are sessile organisms that deal with their -sometimes adverse- environment in well-regulated ways. Chromatin remodeling involving SWI/SNF2-type ATPases is thought to be an important epigenetic mechanism for the regulation of gene expression in different developmental programs and f

  15. Mechanisms of Airway Remodeling in Asthma

    Directory of Open Access Journals (Sweden)

    Etsuko Tagaya

    2007-01-01

    To date, many studies have identified candidate mechanisms and mediators for these observed structural changes, which are thus potential targets in the treatment of asthma. In this review, we describe the recent knowledge of the mechanisms and clinical implications of airway remodeling in asthma.

  16. Revealing remodeler function: Varied and unique

    Science.gov (United States)

    Eastlund, Allen

    Chromatin remodelers perform a necessary and required function for the successful expression of our genetic code. By modifying, shifting, or ejecting nucleosomes from the chromatin structure they allow access to the underlying DNA to the rest of the cell's machinery. This research has focused on two major remodeler motors from major families of chromatin remodelers: the trimeric motor domain of RSC and the motor domain of the ISWI family, ISWI. Using primarily stopped-flow spectrofluorometry, I have categorized the time-dependent motions of these motor domains along their preferred substrate, double-stranded DNA. Combined with collected ATP utilization data, I present the subsequent analysis and associated conclusions that stem from the underlying assumptions and models. Interestingly, there is little in common between the investigated proteins aside from their favored medium. While RSC exhibits modest translocation characteristics and highly effective motion with the ability for large molecular forces, ISWI is not only structurally different but highly inefficient in its motion leading to difficulties in determining its specific translocation mechanics. While chromatin remodeling is a ubiquitous facet of eukaryotic life, there remains much to be understood about their general mechanisms.

  17. 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

  18. Retinal remodeling in human retinitis pigmentosa.

    Science.gov (United States)

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  19. Psoriasis and cardiovascular disease: epidemiology, mechanisms, and clinical implications

    Directory of Open Access Journals (Sweden)

    Pearson KC

    2012-01-01

    Full Text Available Kelly C Pearson1, April W Armstrong21Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 2Department of Dermatology, University of California, Davis, Sacramento, CA, USAAbstract: Psoriasis is a systemic inflammatory disorder, which has been reported to be associated with adverse cardiovascular (CV risks. CV comorbidities, such as diabetes, dyslipidemia, hypertension, and obesity appear to be increased in psoriasis patients compared with the general population. Psoriasis may contribute independently to adverse cardiac outcomes after accounting for traditional CV risk factors. In this article, it was aimed to summarize large population studies that examine the relationship between psoriasis and CV risk factors and major adverse cardiac outcomes, and highlight proposed mechanisms for the observed epidemiologic link. Specifically, large population-based studies with over 1000 total subjects from 1975 to September 2008 in the English literature are highlighted. The relevant search terms in the Ovid Medline database were applied. The majority of the studies presented evidence for an increased incidence of CV risk factors and an increased risk for major adverse cardiac outcomes in patients with severe psoriasis. The increased risk in severe psoriasis necessitates regular screening for other comorbidities. Current guidelines for screening CV risk factors among psoriasis patients are discussed. Also reviewed is the scarce literature in therapeutic strategies to reduce CV risk factors and major adverse cardiac outcomes in psoriasis patients. Specifically, an emerging area of research on the effects of biologic agents on CV risk factors and CV adverse outcomes in psoriasis is discussed.Keywords: cardiovascular disease, cardiovascular risk factors, psoriasis, diabetes mellitus, myocardial infarction, major adverse cardiovascular events, MACE, hypertension

  20. Triglycerides and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Varbo, Anette

    2014-01-01

    cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride......-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk...... of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence...

  1. Cardiovascular disease: primary prevention, disease modulation and regenerative therapy.

    LENUS (Irish Health Repository)

    Sultan, Sherif

    2012-10-01

    Cardiovascular primary prevention and regeneration programs are the contemporary frontiers in functional metabolic vascular medicine. This novel science perspective harnesses our inherent ability to modulate the interface between specialized gene receptors and bioavailable nutrients in what is labeled as the nutrient-gene interaction. By mimicking a natural process through the conveyance of highly absorbable receptor specific nutrients, it is feasible to accelerate cell repair and optimize mitochondrial function, thereby achieving cardiovascular cure. We performed a comprehensive review of PubMed, EMBASE and Cochrane Review databases for articles relating to cardiovascular regenerative medicine, nutrigenomics and primary prevention, with the aim of harmonizing their roles within contemporary clinical practice. We searched in particular for large-scale randomized controlled trials on contemporary cardiovascular pharmacotherapies and their specific adverse effects on metabolic pathways which feature prominently in cardiovascular regenerative programs, such as nitric oxide and glucose metabolism. Scientific research on \\'cardiovascular-free\\' centenarians delineated that low sugar and low insulin are consistent findings. As we age, our insulin level increases. Those who can decelerate the rapidity of this process are prompting their cardiovascular rejuvenation. It is beginning to dawn on some clinicians that contemporary treatments are not only failing to impact on our most prevalent diseases, but they may be causing more damage than good. Primary prevention programs are crucial elements for a better outcome. Cardiovascular primary prevention and regeneration programs have enhanced clinical efficacy and quality of life and complement our conventional endovascular practice.

  2. Gender differences in developmental programming of cardiovascular diseases.

    Science.gov (United States)

    Dasinger, John Henry; Alexander, Barbara T

    2016-03-01

    Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease.

  3. Calcitriol attenuates cardiac remodeling and dysfunction in a murine model of polycystic ovary syndrome.

    Science.gov (United States)

    Gao, Ling; Cao, Jia-Tian; Liang, Yan; Zhao, Yi-Chao; Lin, Xian-Hua; Li, Xiao-Cui; Tan, Ya-Jing; Li, Jing-Yi; Zhou, Cheng-Liang; Xu, Hai-Yan; Sheng, Jian-Zhong; Huang, He-Feng

    2016-05-01

    Polycystic ovary syndrome (PCOS) is a complex reproductive and metabolic disorder affecting 10 % of reproductive-aged women, and is well associated with an increased prevalence of cardiovascular risk factors. However, there are few data concerning the direct association of PCOS with cardiac pathologies. The present study aims to investigate the changes in cardiac structure, function, and cardiomyocyte survival in a PCOS model, and explore the possible effect of calcitriol administration on these changes. PCOS was induced in C57BL/6J female mice by chronic dihydrotestosterone administration, as evidenced by irregular estrous cycles, obesity and dyslipidemia. PCOS mice progressively developed cardiac abnormalities including cardiac hypertrophy, interstitial fibrosis, myocardial apoptosis, and cardiac dysfunction. Conversely, concomitant administration of calcitriol significantly attenuated cardiac remodeling and cardiomyocyte apoptosis, and improved cardiac function. Molecular analysis revealed that the beneficial effect of calcitriol was associated with normalized autophagy function by increasing phosphorylation levels of AMP-activated protein kinase and inhibiting phosphorylation levels of mammalian target of rapamycin complex. Our findings provide the first evidence for the presence of cardiac remodeling in a PCOS model, and vitamin D supplementation may be a potential therapeutic strategy for the prevention and treatment of PCOS-related cardiac remodeling.

  4. Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Jian Yang

    2016-06-01

    Full Text Available Background: In our previous study, farnesyl pyrophosphate synthase (FPPS was shown to be increased in spontaneously hypertensive rats (SHR and in mice with angiotensin-II induced cardiac hypertrophy. Overexpression of FPPS induced cardiac hypertrophy and fibrosis in mice, accompanied by an increase in the synthesis of farnesyl pyrophosphate (FPP and geranylgeranyl pyrophosphate (GGPP. In the present study, we investigated the mechanisms of reversing cardiovascular remodeling in SHR by inhibiting FPPS. Methods and Results: Six-week-old rats were given vehicle or an FPPS inhibitor (alendronate, 100 ug/kg/d daily for twelve weeks by osmotic mini-pump. The results demonstrated that FPPS inhibition attenuated cardiac hypertrophy and fibrosis in SHR as shown by the heart weight to body weight ratio, echocardiographic parameters, and histological examination. In addition, FPPS inhibition attenuated aortic remodeling as shown by reduced media thickness, media cross-sectional area and collagen of the aorta as well as SBP, DBP, MBP. Furthermore, 12 weeks of alendronate treatment significantly decreased FPP and GGPP levels, RhoA activation and geranylgeranylation in the heart and aorta, all of which were significantly upregulated in SHR compared with normotensive Wistar-Kyoto rats. Conclusion: Taken together, these results indicate that chronic treatment with alendronate decreases the development of cardiac and aortic remodeling, by a pathway which involves inhibition of the geranylgeranylation and activation of RhoA.

  5. Effects of the use of assisted reproduction and high-caloric diet consumption on body weight and cardiovascular health of juvenile mouse offspring.

    Science.gov (United States)

    Schenewerk, Angela L; Ramírez, Francisco Í; Foote, Christopher; Ji, Tieming; Martínez-Lemus, Luis A; Rivera, Rocío Melissa

    2014-01-01

    Maternal obesity and the use of assisted reproductive technologies (ART) are two suboptimal developmental environments that can lead to offspring obesity and cardiovascular disease. We hypothesized that these environments independently and synergistically adversely affect the offspring's weight and cardiovascular performance at ~7 weeks of age. Mice were fed either 24% fat and 17.5% high-fructose (HF) corn syrup or maintenance chow (5% fat; low-fat, no-fructose (LF)). Dams were subdivided into no ART and ART groups. ART embryos were cultured in Whitten's medium and transferred into pseudopregnant recipients consuming the same diet as the donor. Offspring were fed the same diet as the mother. Body weights (BW) were measured weekly and mean arterial pressure (MAP) was collected through carotid artery catheterization at killing (55±0.5 days old). Expression of genes involved in cardiovascular remodeling was measured in thoracic aorta using qRT-PCR, and levels of reactive oxygen species (ROS) were measured intracellularly and extracellularly in mesenteric resistance arteries. ART resulted in increased BW at weaning. This effect decreased over time and diet was the predominant determinant of BW by killing. Males had greater MAP than females (P=0.002) and HF consumption was associated with greater MAP regardless of sex (P<0.05). Gene expression was affected by sex (P<0.05) and diet (P<0.1). Lastly, the use of ART resulted in offspring with increased intracellular ROS (P=0.05). In summary, exposure to an obesogenic diet pre- and/or post-natally affects weight, MAP, and gene expression while ART increases oxidative stress in mesenteric resistance arteries of juvenile offspring, no synergistic effects were observed.

  6. Fermented Wheat Germ Extract (Avemar in the Treatment of Cardiac Remodeling and Metabolic Symptoms in Rats

    Directory of Open Access Journals (Sweden)

    Abishek Iyer

    2011-01-01

    Full Text Available Avemar, a product of industrial fermentation of wheat germ with a standardized content of benzoquinone and plant flavonoids, has been tested as an anti-cancer and immunomodulatory dietary supplement. Proposed mechanisms include anti-oxidant and anti-inflammatory actions. This study has determined whether these actions of Avemar may also be useful in the treatment of cardiovascular diseases. Two experimental rat models of cardiovascular remodeling were used in this project: the deoxycorticosterone acetate (DOCA-salt-induced model of chronic hypertension (study I and a high-carbohydrate/high-fat diet-induced model producing chronic symptoms of the metabolic syndrome and its associated cardiovascular complications (study II. Our results in these rat models of hypertension and diet-induced obesity show that treatment with Avemar improved cardiac function, decreased macrophage infiltration resulting in decreased collagen deposition in the ventricular myocardium, reversed an increased stiffness of the left ventricle in the diseased hearts and attenuated increased plasma malondialdehyde concentrations. In addition to the changes in the heart, Avemar reversed glucose intolerance, normalized systolic blood pressure and decreased visceral fat deposition in rats fed a high-fat/high-carbohydrate diet. In conclusion, the fermented wheat germ extract Avemar has a potential role in attenuating chronic hypertension, diabetes or metabolic syndrome-induced cardiovascular symptoms along with metabolic abnormalities such as glucose tolerance and obesity.

  7. Fermented wheat germ extract (avemar) in the treatment of cardiac remodeling and metabolic symptoms in rats.

    Science.gov (United States)

    Iyer, Abishek; Brown, Lindsay

    2011-01-01

    Avemar, a product of industrial fermentation of wheat germ with a standardized content of benzoquinone and plant flavonoids, has been tested as an anti-cancer and immunomodulatory dietary supplement. Proposed mechanisms include anti-oxidant and anti-inflammatory actions. This study has determined whether these actions of Avemar may also be useful in the treatment of cardiovascular diseases. Two experimental rat models of cardiovascular remodeling were used in this project: the deoxycorticosterone acetate (DOCA)-salt-induced model of chronic hypertension (study I) and a high-carbohydrate/high-fat diet-induced model producing chronic symptoms of the metabolic syndrome and its associated cardiovascular complications (study II). Our results in these rat models of hypertension and diet-induced obesity show that treatment with Avemar improved cardiac function, decreased macrophage infiltration resulting in decreased collagen deposition in the ventricular myocardium, reversed an increased stiffness of the left ventricle in the diseased hearts and attenuated increased plasma malondialdehyde concentrations. In addition to the changes in the heart, Avemar reversed glucose intolerance, normalized systolic blood pressure and decreased visceral fat deposition in rats fed a high-fat/high-carbohydrate diet. In conclusion, the fermented wheat germ extract Avemar has a potential role in attenuating chronic hypertension, diabetes or metabolic syndrome-induced cardiovascular symptoms along with metabolic abnormalities such as glucose tolerance and obesity.

  8. Toxic urban waste's assault on cardiovascular risk

    Directory of Open Access Journals (Sweden)

    M.L. De Rosa

    2015-03-01

    Full Text Available A cardiovascular health survey of 1203 persons in households located near the hazardous waste disposal sites and in a reference community, was conducted from 2009 until today to assess whether rates of adverse cardiovascular health outcomes were elevated among persons living near the sites. Data included medical records of reported cardiovascular disease certificates and hospital admission for cardiovascular diseases from hospital database. The study areas appeared similar with respect to mortality, cancer incidence, and pregnancy outcomes. In contrast, rate ratios were greater than 1.5 for 2 of 19 reported diseases, i.e., angina pectoris, and strokes. The apparent broad-based elevation in reported diseases and symptoms may reflect increased perception or recall of conditions by respondents living near the sites. Our study found that cardiovascular risk is associated only with PM2.5 concentrations, derived from uncontrolled burning of municipal solid waste in particular sites of our country. Their analysis demonstrated a relationship between increased levels of eventual fine particulate pollution and higher rates of death and complications from cardiovascular and cerebrovascular diseases. Management of solid waste releases a number of toxic substances, most in small quantities and at extremely low levels. Because of the wide range of pollutants, the different pathways of exposure, long-term low-level exposure, and the potential for synergism among the pollutants, concerns remain about potential health effects but there are many uncertainties involved in the assessment. Future community-based health studies should include medical and psychosocial assessment instruments sufficient to distinguish between changes in health status and effects of resident reporting tendency.

  9. Vitamin D, cardiovascular disease and mortality.

    Science.gov (United States)

    Pilz, Stefan; Tomaschitz, Andreas; März, Winfried; Drechsler, Christiane; Ritz, Eberhard; Zittermann, Armin; Cavalier, Etienne; Pieber, Thomas R; Lappe, Joan M; Grant, William B; Holick, Michael F; Dekker, Jacqueline M

    2011-11-01

    A poor vitamin D status, i.e. low serum levels of 25-hydroxyvitamin D [25(OH)D], is common in the general population. This finding is of concern not only because of the classic vitamin D effects on musculoskeletal outcomes, but also because expression of the vitamin D receptor (VDR) and vitamin D metabolizing enzymes in the heart and blood vessels suggests a role of vitamin D in the cardiovascular system. VDR-knockout mice suffer from cardiovascular disease (CVD), and various experimental studies suggest cardiovascular protection by vitamin D, including antiatherosclerotic, anti-inflammatory and direct cardio-protective actions, beneficial effects on classic cardiovascular risk factors as well as suppression of parathyroid hormone (PTH) levels. In epidemiological studies, low levels of 25(OH)D are associated with increased risk of CVD and mortality. Data from randomized controlled trials (RCTs) are sparse and have partially, but not consistently, shown some beneficial effects of vitamin D supplementation on cardiovascular risk factors (e.g. arterial hypertension). We have insufficient data on vitamin D effects on cardiovascular events, but meta-analyses of RCTs indicate that vitamin D may modestly reduce all-cause mortality. Despite accumulating data suggesting that a sufficient vitamin D status may protect against CVD, we still must wait for results of large-scale RCTs before raising general recommendations for vitamin D in the prevention and treatment of CVD. In current clinical practice, the overall risks and costs of vitamin D supplementation should be weighed against the potential adverse consequences of untreated vitamin D deficiency.

  10. The RSC chromatin remodeling complex has a crucial role in the complete remodeler set for yeast PHO5 promoter opening.

    Science.gov (United States)

    Musladin, Sanja; Krietenstein, Nils; Korber, Philipp; Barbaric, Slobodan

    2014-04-01

    Although yeast PHO5 promoter chromatin opening is a founding model for chromatin remodeling, the complete set of involved remodelers remained unknown for a long time. The SWI/SNF and INO80 remodelers cooperate here, but nonessentially, and none of the many tested single or combined remodeler gene mutations could prevent PHO5 promoter opening. RSC, the most abundant and only remodeler essential for viability, was a controversial candidate for the unrecognized remodeling activity but unassessed in vivo. Now we show that remodels the structure of chromatin (RSC) is crucially involved in PHO5 promoter opening. Further, the isw1 chd1 double deletion also delayed chromatin remodeling. Strikingly, combined absence of RSC and Isw1/Chd1 or Snf2 abolished for the first time promoter opening on otherwise sufficient induction in vivo. Together with previous findings, we recognize now a surprisingly complex network of five remodelers (RSC, SWI/SNF, INO80, Isw1 and Chd1) from four subfamilies (SWI/SNF, INO80, ISWI and CHD) as involved in PHO5 promoter chromatin remodeling. This is likely the first described complete remodeler set for a physiological chromatin transition. RSC was hardly involved at the coregulated PHO8 or PHO84 promoters despite cofactor recruitment by the same transactivator and RSC's presence at all three promoters. Therefore, promoter-specific chromatin rather than transactivators determine remodeler requirements.

  11. Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

    Science.gov (United States)

    Schiffrin, Ernesto L

    2015-12-04

    This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.

  12. Introduction: Cardiovascular physics.

    Science.gov (United States)

    Wessel, Niels; Kurths, Jürgen; Ditto, William; Bauernschmitt, Robert

    2007-03-01

    The number of patients suffering from cardiovascular diseases increases unproportionally high with the increase of the human population and aging, leading to very high expenses in the public health system. Therefore, the challenge of cardiovascular physics is to develop high-sophisticated methods which are able to, on the one hand, supplement and replace expensive medical devices and, on the other hand, improve the medical diagnostics with decreasing the patient's risk. Cardiovascular physics-which interconnects medicine, physics, biology, engineering, and mathematics-is based on interdisciplinary collaboration of specialists from the above scientific fields and attempts to gain deeper insights into pathophysiology and treatment options. This paper summarizes advances in cardiovascular physics with emphasis on a workshop held in Bad Honnef, Germany, in May 2005. The meeting attracted an interdisciplinary audience and led to a number of papers covering the main research fields of cardiovascular physics, including data analysis, modeling, and medical application. The variety of problems addressed by this issue underlines the complexity of the cardiovascular system. It could be demonstrated in this Focus Issue, that data analyses and modeling methods from cardiovascular physics have the ability to lead to significant improvements in different medical fields. Consequently, this Focus Issue of Chaos is a status report that may invite all interested readers to join the community and find competent discussion and cooperation partners.

  13. Association Between Myocardial Mechanics and Ischemic LV Remodeling.

    Science.gov (United States)

    D'Elia, Nicholas; D'hooge, Jan; Marwick, Thomas H

    2015-12-01

    The outcomes associated with heart failure after myocardial infarction are still poor. Both global and regional left ventricular (LV) remodeling are associated with the progression of the post-infarct patient to heart failure, but although global remodeling can be accurately measured, regional LV remodeling has been more difficult to investigate. Preliminary evidence suggests that post-MI assessment of LV mechanics using stress and strain may predict global (and possibly regional) LV remodeling. A method of predicting both global and regional LV remodeling might facilitate earlier, targeted, and more extensive clinical intervention in those most likely to benefit from novel interventions such as cell therapy.

  14. Cardiovascular comorbiditiy in psoriasis

    Directory of Open Access Journals (Sweden)

    Gurcharan Singh

    2011-01-01

    Full Text Available The chronic inflammatory nature of psoriasis is also thought to predispose patients to other diseases with an inflammatory component, the most notable being cardiovascular and metabolic (cardiometabolite disorders. This concept is supported by studies showing that psoriasis is associated with cardiovascular risk factors like diabetes, obesity, hypertension, dyslipidemia, smoking and diseases including MI. Given the increased prevalence of cardiovascular co morbidities in patients, dermatologists treating psoriasis need to approach the disease as a potentially multisystem disorder and must alert these patients to the potentially negative effects of their disease.

  15. Urocortin and cardiovascular protection

    Institute of Scientific and Technical Information of China (English)

    Yu HUANG; Xiao-qiang YAO; Chi-wai LAU; Yau-chi CHAN; Suk-ying TSANG; Franky Leung CHAN

    2004-01-01

    Urocortin and other hypothalamus corticotropin-releasing factor (CRF) polypeptides play biologically diverse roles in the stress, cardiovascular and inflammatory responses by acting on central and peripheral CRF receptors.Urocortin shows a significantly high sequence homology to CRF, and the concurrent expression of type-2 CRF (CRF2) receptors with urocortin in the heart suggests that urocortin may play a physiological role in the cardiac function. Urocortin is thought to be the endogenous agonist producing the cardiovascular actions previously attributed to CRF. This review highlights the current novel findings on the molecular and cellular mechanisms by which urocortin may exert its cardiovascular protective action.

  16. Mental stress and human cardiovascular disease.

    Science.gov (United States)

    Esler, Murray

    2017-03-01

    The London physician and neuroanatomist Thomas Willis in the 17th century correctly attributed the source of emotions to the brain, not the heart as believed in antiquity. Contemporary research documents the phenomenon of "triggered" heart disease, when the autonomic nervous system control of the heart by the brain goes awry, producing heart disease of sudden onset, precipitated by acute emotional upheaval. This can take the form of, variously, cardiac arrhythmias, myocardial infarction, Takotsubo cardiomyopathy and sudden death. Chronic psychological distress also can have adverse cardiovascular consequences, in the causal linkage of depressive illness to heart disease, and in the probable causation of atherosclerosis and hypertension by chronic mental stress. In patients with essential hypertension, stress biomarkers are present. The sympathetic nervous system is the usual mediator between these acute and chronic psychological substrates and cardiovascular disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    Izeli, Nataly Lino; Santos, Aurélia Juliana dos; Crescêncio, Júlio César; Gonçalves, Ana Clara Campagnolo Real; Papa, Valéria; Marques, Fabiana [Divisão de Cardiologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP (Brazil); Pazin-Filho, Antônio [Divisão de Emergência da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP (Brazil); Gallo-Júnior, Lourenço; Schmidt, André, E-mail: aschmidt@fmrp.usp.br [Divisão de Cardiologia do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP, Ribeirão Preto, SP (Brazil)

    2016-04-15

    Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). 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. 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). 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.

  18. Left ventricular remodeling and fibrosis: Sex differences and relationship with diastolic function in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, You-Zhou [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Qiao, Shu-Bin, E-mail: qsbfw@sina.com [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Hu, Feng-Huan; Yuan, Jian-Song; Yang, Wei-Xian; Cui, Jin-Gang [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Yan [Department of Radiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Zhang, Chang-Lin [Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China)

    2015-08-15

    Highlights: • There are significant differences in LV remodeling and fibrosis as divided by sex. • Women have worse diastolic dysfunction compared to men measured by CMR. • LV remodeling and fibrosis correlate with markers of diastolic dysfunction. - Abstract: Objectives: We investigated sex differences in left ventricular (LV) remodeling and fibrosis and their relationship with LV diastolic dysfunction by cardiovascular magnetic resonance (CMR). Methods: CMR imaging was performed simultaneously in 152 age-matched patients (76 men, 76 women; mean age: 49 ± 9 years) without LV systolic dysfunction. LV remodeling index (LVRI) was calculated as the ratio of LV mass and end-diastolic volume. Diastolic function indexes including peak filling rate (PFR) and time to PFR (tPFR) were evaluated. Extent of late gadolinium enhancement (LGE) was measured. Results: LVRI and extent of LGE were greater in women compared with men (1.48 ± 0.22 vs. 1.36 ± 0.28 g/ml; 13.15 ± 2.48 vs. 11.35 ± 2.34 g, respectively, both P < 0.001). Women had lower PFR and higher tPFR (both P < 0.001) than men. LVRI and the extent of LGE showed significant relationships with parameters of diastolic function in both sex. In a multivariate analysis, LVRI remained a strong independent predictor of PFR and TPFR in women (β = −0.272, P = 0.032; β = 0.348, P = 0.016, respectively), and in men (β = −0.374, P < 0.001; β = 0.660, P < 0.001, respectively). Furthermore, the extent of LGE also remained an independent predictor of PFR in women (β = −0.283, P = 0.033) and men (β = −0.492, P < 0.001). Conclusions: There are prominent sex differences in LV remodeling and myocardial fibrosis. We suggest that the effects of LV remodeling and fibrosis may lead to diastolic dysfunction with greater susceptibility to worse clinical outcome in women.

  19. Cardiovascular effects of current and future anti-obesity drugs

    DEFF Research Database (Denmark)

    Comerma-Steffensen, Simon; Grann, Martin; Andersen, Charlotte

    2014-01-01

    The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have...... reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased...... cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular...

  20. Cardiovascular manifestations in hyperthyroidism

    Directory of Open Access Journals (Sweden)

    Vairamani Kandan

    2016-07-01

    Conclusions: This study shows that cardiovascular manifestations are quite common and varied in hyperthyroidism which are to be looked for in the management. [Int J Res Med Sci 2016; 4(7.000: 3032-3038

  1. Cardiovascular modeling and diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Kangas, L.J.; Keller, P.E.; Hashem, S.; Kouzes, R.T. [Pacific Northwest Lab., Richland, WA (United States)

    1995-12-31

    In this paper, a novel approach to modeling and diagnosing the cardiovascular system is introduced. A model exhibits a subset of the dynamics of the cardiovascular behavior of an individual by using a recurrent artificial neural network. Potentially, a model will be incorporated into a cardiovascular diagnostic system. This approach is unique in that each cardiovascular model is developed from physiological measurements of an individual. Any differences between the modeled variables and the variables of an individual at a given time are used for diagnosis. This approach also exploits sensor fusion to optimize the utilization of biomedical sensors. The advantage of sensor fusion has been demonstrated in applications including control and diagnostics of mechanical and chemical processes.

  2. Depressive Symptoms and Risk of New Cardiovascular Events or Death in Patients with Myocardial Infarction

    DEFF Research Database (Denmark)

    Larsen, Karen Kjær; Christensen, Bo; Søndergaard, Jens;

    2013-01-01

    of new cardiovascular events and/or death in patients with depressive symptoms following first-time MI taking into account other secondary preventive factors. We further explored whether we could identify subgroups of patients with a particularly high relative risk of adverse outcomes.......Depressive symptoms is associated with adverse cardiovascular outcomes in patients with myocardial infarction (MI), but the underlying mechanisms are unclear and it remains unknown whether subgroups of patients are at a particularly high relative risk of adverse outcomes. We examined the risk...

  3. Metabolic remodeling in chronic heart failure

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Tao GUO

    2013-01-01

    Although the management of chronic heart failure (CHF) has made enormous progress over the past decades,CHF is still a tremendous medical and societal burden.Metabolic remodeling might play a crucial role in the pathophysiology of CHF.The characteristics and mechanisms of metabolic remodeling remained unclear,and the main hypothesis might include the changes in the availability of metabolic substrate and the decline of metabolic capability.In the early phases of the disease,metabolism shifts toward carbohydrate utilization from fatty acids (FAs) oxidation.Along with the progress of the disease,the increasing level of the hyperadrenergic state and insulin resistance cause the changes that shift back to a greater FA uptake and oxidation.In addition,a growing body of experimental and clinical evidence suggests that the improvement in the metabolic capability is likely to be more significant than the selection of the substrate.

  4. Dynamic Insurance and Adverse Selection

    NARCIS (Netherlands)

    M.C.W. Janssen (Maarten); V.A. Karamychev (Vladimir)

    2001-01-01

    textabstractWe take a dynamic perspective on insurance markets under adverse selection and study a generalized Rothschild and Stiglitz model where agents may differ with respect to the accidental probability and their expenditure levels in case an accident occurs. We investigate the nature of dynami

  5. 急性冠脉综合征患者Lp-PLA2水平对短期心血管不良预后的影响%Effect of lipoprotein-associated phospholipase A2 level on prognosis of short-term adverse cardiovascular outcomes in patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    花颖

    2015-01-01

    group and low level group. The primary cardiovascular events and the involved cardiovascular events within 30 days were analyzed. Results: The Lp-PLA2 Levels was significantly higher in ACS group compared with control group ( P<0 . 01 ) . In hospital , there was no correlation between the Lp-PLA2 levels and the incidence of the primary cardiovascular events(P=0.230). However at 30-day follow-up, patients in high Lp-PLA2 level group had a significantly higher incidence of the combined cardiovascular events than those in low level group(P<0.01). The logistics regression analysis displayed that Lp-PLA2 is an independent risk factors which may predict the combined cardiovascular events of ACS patients within 30 days after admission. Conclusion: Lp-PLA2 is an independent predictive biomarker in the risk stratification of ACS patients within 30 days after onset.

  6. Stepwise nucleosome translocation by RSC remodeling complexes.

    Science.gov (United States)

    Harada, Bryan T; Hwang, William L; Deindl, Sebastian; Chatterjee, Nilanjana; Bartholomew, Blaine; Zhuang, Xiaowei

    2016-02-19

    The SWI/SNF-family remodelers regulate chromatin structure by coupling the free energy from ATP hydrolysis to the repositioning and restructuring of nucleosomes, but how the ATPase activity of these enzymes drives the motion of DNA across the nucleosome remains unclear. Here, we used single-molecule FRET to monitor the remodeling of mononucleosomes by the yeast SWI/SNF remodeler, RSC. We observed that RSC primarily translocates DNA around the nucleosome without substantial displacement of the H2A-H2B dimer. At the sites where DNA enters and exits the nucleosome, the DNA moves largely along or near its canonical wrapping path. The translocation of DNA occurs in a stepwise manner, and at both sites where DNA enters and exits the nucleosome, the step size distributions exhibit a peak at approximately 1-2 bp. These results suggest that the movement of DNA across the nucleosome is likely coupled directly to DNA translocation by the ATPase at its binding site inside the nucleosome.

  7. Psoriatic architecture constructed by epidermal remodeling.

    Science.gov (United States)

    Iizuka, Hajime; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2004-08-01

    Epidermal remodeling is the concept that epidermal architecture is determined by a simple self-organizing mechanism; epidermal hyperproliferation constructs typical psoriatic architecture. This is based on the assumption that the enlargements in both the two-dimensional proliferative compartment (basal cell layer) and three-dimensional whole epidermal volume coexist. During this process, the dermal papillae become markedly, but passively, expanded by enlargement of the proliferative compartment. This creates a considerable shrinkage force against the crowded basal cell layer, which is forced to lose adherence to the dermal extracellular matrix (ECM). This results in anoikis, a type of apoptosis characterized by cell detachment, and, consequently, a markedly diminished epidermal turnover time in psoriasis. The papillary shrinkage force also explains the fact that dermal papillary height does not exceed a certain limit. At the cessation of hyperproliferation a normalisation remodeling takes place toward normal tissue architecture. Thus the concept of epidermal remodeling explains the self-organizing mechanism of the architectural change in psoriasis, which is essentially a reversible disorder depending on epidermal hyperproliferation.

  8. Bone Remodelling Markers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Patrice Fardellone

    2014-01-01

    Full Text Available Bone loss in rheumatoid arthritis (RA patients results from chronic inflammation and can lead to osteoporosis and fractures. A few bone remodeling markers have been studied in RA witnessing bone formation (osteocalcin, serum aminoterminal propeptide of type I collagen (PINP, serum carboxyterminal propeptide of type I collagen (ICTP, bone alkaline phosphatase (BAP, osteocalcin (OC, and bone resorption: C-terminal telopeptide of type 1 collagen (I-CTX, N-terminal telopeptide of type 1 collagen (I-NTX, pyridinolines (DPD and PYD, and tartrate-resistant acid phosphatase (TRAP. Bone resorption can be seen either in periarticular bone (demineralization and erosion or in the total skeleton (osteoporosis. Whatever the location, bone resorption results from activation of osteoclasts when the ratio between osteoprotegerin and receptor activator of nuclear factor kappa-B ligand (OPG/RANKL is decreased under influence of various proinflammatory cytokines. Bone remodeling markers also allow physicians to evaluate the effect of drugs used in RA like biologic agents, which reduce inflammation and exert a protecting effect on bone. We will discuss in this review changes in bone markers remodeling in patients with RA treated with biologics.

  9. Tissue Remodelling following Resection of Porcine Liver

    Directory of Open Access Journals (Sweden)

    Ingvild Engdal Nygård

    2015-01-01

    Full Text Available Aim. To study genes regulating the extracellular matrix (ECM and investigate the tissue remodelling following liver resection in porcine. Methods. Four pigs with 60% partial hepatectomy- (PHx- induced liver regeneration were studied over six weeks. Four pigs underwent sham surgery and another four pigs were used as controls of the normal liver growth. Liver biopsies were taken upon laparotomy, after three and six weeks. Gene expression profiles were obtained using porcine-specific oligonucleotide microarrays. Immunohistochemical staining was performed and a proliferative index was assessed. Results. More differentially expressed genes were associated with the regulation of ECM in the resection group compared to the sham and control groups. Secreted protein acidic and rich in cysteine (SPARC and collagen 1, alpha 2 (COL1A2 were both upregulated in the early phase of liver regeneration, validated by immunopositive cells during the remodelling phase of liver regeneration. A broadened connective tissue was demonstrated by Masson’s Trichrome staining, and an immunohistochemical staining against pan-Cytokeratin (pan-CK demonstrated a distinct pattern of migrating cells, followed by proliferating cell nuclear antigen (PCNA positive nuclei. Conclusions. The present study demonstrates both a distinct pattern of PCNA positive nuclei and a deposition of ECM proteins in the remodelling phase of liver regeneration.

  10. Adverse Effects of Hormonal Contraception

    Directory of Open Access Journals (Sweden)

    Sabatini R

    2011-01-01

    Full Text Available contraception acceptability, compliance and continuation. Despite the safety profile of current COCs, fears of adverse metabolic and vascular effects caused by estrogen component, and possible neoplastic effects of these formulations remain. Misperceptions and concerns about side-effects, especially those affecting the menstrual cycle and increased body weight, are often given as reason for discontinuation. Besides, severe adverse effects exist; perhaps they are very rare, but it might be that other cases were underestimated or ignored. It is important to take into account that COCs, as all medications, have some contraindications, which is mandatory to consider. The „pill“ could be not for everyone. In any case, also mild or moderate adverse effects of COCs may impair the woman’s quality of life. It is well known that even small increases in frequency of adverse effects, in COCs-users, could have a general critical health impact because of their widespread use, which is currently expanding to potential risk groups. To avoid adverse events by COC use the exclusion of patients with known risk factors including patient history and family history is necessary. Furthermore the patient should be informed about possible side effects and side effects during OC use should be carefully monitored. Finally the risk benefit analysis for oral contraceptive pills which are worldwide used since more than 50 years for healthy patients is positive. Most women will benefit from additional noncontraceptive benefits such as improvement of acne vulgaris, dysmenorrhoea, stabilization of menstrual bleeding pattern, less ovarian cysts and finally a lower risk for ovarian and breast cancer, which persists even after withdrawl of COC for several years.

  11. Aggravated myocardial infarction-induced cardiac remodeling and heart failure in histamine-deficient mice

    Science.gov (United States)

    Chen, Jinmiao; Hong, Tao; Ding, Suling; Deng, Long; Abudupataer, Mieradilijiang; Zhang, Weiwei; Tong, Minghong; Jia, Jianguo; Gong, Hui; Zou, Yunzeng; Wang, Timothy C.; Ge, Junbo; Yang, Xiangdong

    2017-01-01

    Histamine has pleiotropic pathophysiological effects, but its role in myocardial infarction (MI)-induced cardiac remodeling remains unclear. Histidine decarboxylase (HDC) is the main enzyme involved in histamine production. Here, we clarified the roles of HDC-expressing cells and histamine in heart failure post-MI using HDC-EGFP transgenic mice and HDC-knockout (HDC−/−) mice. HDC+CD11b+ myeloid cell numbers markedly increased in the injured hearts, and histamine levels were up-regulated in the circulation post-MI. HDC−/− mice exhibited more adverse cardiac remodeling, poorer left ventricular function and higher mortality by increasing cardiac fibrogenesis post-MI. In vitro assays further confirmed that histamine inhibited heart fibroblast proliferation. Furthermore, histamine enhanced the signal transducer and activator of transcription (STAT)-6 phosphorylation level in murine heart fibroblasts, and the inhibitive effects of histamine on fibroblast proliferation could be blocked by JAK3/STAT6 signaling selective antagonist. STAT6-knockout (STAT6−/−) mice had a phenotype similar to that of HDC−/− mice post-MI; however, in contrast to HDC−/− mice, the beneficial effects of exogenous histamine injections were abrogated in STAT6−/− mice. These data suggest that histamine exerts protective effects by modulating cardiac fibrosis and remodeling post-MI, in part through the STAT6-dependent signaling pathway. PMID:28272448

  12. Mental stress-induced left ventricular dysfunction and adverse outcome in ischemic heart disease patients.

    Science.gov (United States)

    Sun, Julia L; Boyle, Stephen H; Samad, Zainab; Babyak, Michael A; Wilson, Jennifer L; Kuhn, Cynthia; Becker, Richard C; Ortel, Thomas L; Williams, Redford B; Rogers, Joseph G; O'Connor, Christopher M; Velazquez, Eric J; Jiang, Wei

    2017-04-01

    Aims Mental stress-induced myocardial ischemia (MSIMI) occurs in up to 70% of patients with clinically stable ischemic heart disease and is associated with increased risk of adverse prognosis. We aimed to examine the prognostic value of indices of MSIMI and exercise stress-induced myocardial ischemia (ESIMI) in a population of ischemic heart disease patients that was not confined by having a recent positive physical stress test. Methods and results The Responses of Mental Stress Induced Myocardial Ischemia to Escitalopram Treatment (REMIT) study enrolled 310 subjects who underwent mental and exercise stress testing and were followed annually for a median of four years. Study endpoints included time to first and total rate of major adverse cardiovascular events, defined as all-cause mortality and hospitalizations for cardiovascular causes. Cox and negative binomial regression adjusting for age, sex, resting left ventricular ejection fraction, and heart failure status were used to examine associations of indices of MSIMI and ESIMI with study endpoints. The continuous variable of mental stress-induced left ventricular ejection fraction change was significantly associated with both endpoints (all p values mental stress, patients had a 5% increase in the probability of a major adverse cardiovascular event at the median follow-up time and a 20% increase in the number of major adverse cardiovascular events endured over the follow-up period of six years. Indices of ESIMI did not predict endpoints ( ps > 0.05). Conclusion In patients with stable ischemic heart disease, mental, but not exercise, stress-induced left ventricular ejection fraction change significantly predicts risk of future adverse cardiovascular events.

  13. Rho-kinase inhibition in the therapy of cardiovascular disease.

    Science.gov (United States)

    Lai, Andrew; Frishman, William H

    2005-01-01

    Rho is a GTPase known to be a major mediator in the formation of stress fibers and focal adhesions, cell morphology, and smooth muscle contraction. Its role in smooth muscle contraction has led to exploration into the connection between Rho-mediated kinase activity and cardiovascular disease. The role of Rho-kinase in calcium sensitization for vascular smooth muscle contraction has recently been characterized. Inappropriate coronary artery vasoconstriction resulting from increased Rho-kinase in the vascular system is likely involved in the pathogenesis of exercise-induced myocardial ischemia, spontaneous coronary artery spasm, and hypertension. In clinical trials, Rho-kinase inhibitors such as fasudil and Y-27632 have demonstrated antiischemic, antivasospastic, and antihypertensive effects. These compounds have also exhibited the ability to blunt progression of cardiomyocyte hypertrophy and cardiac remodeling in heart failure. As such, Rho-kinase inhibition represents a potential novel therapeutic approach in cardiovascular disease.

  14. [Vitamin D and cardiovascular risk].

    Science.gov (United States)

    Mayer, Otto

    2012-05-01

    The pathogenesis of cardiovascular disease is without any doubt multifactorial, and it is generally accepted, that conventional risk factors determined only about 80% of cardiovascular risk. There is accumulating evidence that vitamin D exerts important pathophysiological effects on cardiovascular system. Low vitamin D was associated with increased cardiovascular risk in several reports. This review summarizes recent epidemiological evidence and possible pathophysiological mechanism for a role of low vitamin D in cardiovascular diseases. Moreover, available data concerning vitamin D supplementation are depicted.

  15. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Martin, Tamara P.; Hortigon-Vinagre, Maria P.; Findlay, Jane E.; Elliott, Christina; Currie, Susan; Baillie, George S.

    2014-01-01

    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. PMID:25426411

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

    Science.gov (United States)

    Martin, Tamara P; Hortigon-Vinagre, Maria P; Findlay, Jane E; Elliott, Christina; Currie, Susan; Baillie, George S

    2014-01-01

    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.

  19. Multidetector computed tomography predictors of late ventricular remodeling and function after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Lessick, Jonathan, E-mail: j_lessick@rambam.health.gov.il [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Abadi, Sobhi [Medical Imaging Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Agmon, Yoram [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Keidar, Zohar [Nuclear Medicine Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Carasso, Shemi; Aronson, Doron [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Ghersin, Eduard [Department of Diagnostic Radiology, University of Miami, Miller School of Medicine, Miami, FL (United States); Rispler, Shmuel [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Sebbag, Anat [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Israel, Ora [Nuclear Medicine Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel); Hammerman, Haim; Roguin, Ariel [Cardiology Department, Rambam Health Care Campus, Haaliya Street, Haifa (Israel); Technion-IIT, Haaliya Street, Haifa (Israel)

    2012-10-15

    Background: Despite advent of rapid arterial revascularization as 1st line treatment for acute myocardial infarction (AMI), incomplete restoral of flow at the microvascular level remains a problem and is associated with adverse prognosis, including pathological ventricular remodeling. We aimed to study the association between multidetector row computed tomography (MDCT) perfusion defects and ventricular remodeling post-AMI. Methods: In a prospective study, 20 patients with ST-elevation AMI, treated by primary angioplasty, underwent arterial and late phase MDCT as well as radionuclide scans to study presence, size and severity of myocardial perfusion defects. Contrast echocardiography was performed at baseline and at 4 months follow-up to evaluate changes in myocardial function and remodeling. Results: Early defects (ED), late defects (LD) and late enhancement (LE) were detected in 15, 7 and 16 patients, respectively and radionuclide defects in 15 patients. The ED area (r = 0.74), and LD area (r = 0.72), and to a lesser extent LE area (r = 0.62) correlated moderately well with SPECT summed rest score. By univariate analysis, follow-up end-systolic volume index and ejection fraction were both significantly related to ED and LD size and severity, but not to LE size or severity. By multivariate analysis, end-systolic volume index was best predicted by LD area (p < 0.05) and ejection fraction by LD enhancement ratio. Conclusions: LD size and severity on MDCT are most closely associated with pathological ventricular remodeling after AMI and may thus play a role in early identification and treatment of this condition.

  20. Adverse health effects of high-effort/low-reward conditions.

    Science.gov (United States)

    Siegrist, J

    1996-01-01

    In addition to the person-environment fit model (J. R. French, R. D. Caplan, & R. V. Harrison, 1982) and the demand-control model (R. A. Karasek & T. Theorell, 1990), a third theoretical concept is proposed to assess adverse health effects of stressful experience at work: the effort-reward imbalance model. The focus of this model is on reciprocity of exchange in occupational life where high-cost/low-gain conditions are considered particularly stressful. Variables measuring low reward in terms of low status control (e.g., lack of promotion prospects, job insecurity) in association with high extrinsic (e.g., work pressure) or intrinsic (personal coping pattern, e.g., high need for control) effort independently predict new cardiovascular events in a prospective study on blue-collar men. Furthermore, these variables partly explain prevalence of cardiovascular risk factors (hypertension, atherogenic lipids) in 2 independent studies. Studying adverse health effects of high-effort/low-reward conditions seems well justified, especially in view of recent developments of the labor market.

  1. Rho kinases in cardiovascular physiology and pathophysiology: the effect of fasudil.

    Science.gov (United States)

    Shi, Jianjian; Wei, Lei

    2013-10-01

    Rho kinase (ROCK) is a major downstream effector of the small GTPase RhoA. ROCK family, consisting of ROCK1 and ROCK2, plays central roles in the organization of actin cytoskeleton and is involved in a wide range of fundamental cellular functions, such as contraction, adhesion, migration, proliferation, and apoptosis. Due to the discovery of effective inhibitors, such as fasudil and Y27632, the biological roles of ROCK have been extensively explored with particular attention on the cardiovascular system. In many preclinical models of cardiovascular diseases, including vasospasm, arteriosclerosis, hypertension, pulmonary hypertension, stroke, ischemia-reperfusion injury, and heart failure, ROCK inhibitors have shown a remarkable efficacy in reducing vascular smooth muscle cell hypercontraction, endothelial dysfunction, inflammatory cell recruitment, vascular remodeling, and cardiac remodeling. Moreover, fasudil has been used in the clinical trials of several cardiovascular diseases. The continuing utilization of available pharmacological inhibitors and the development of more potent or isoform-selective inhibitors in ROCK signaling research and in treating human diseases are escalating. In this review, we discuss the recent molecular, cellular, animal, and clinical studies with a focus on the current understanding of ROCK signaling in cardiovascular physiology and diseases. We particularly note that emerging evidence suggests that selective targeting ROCK isoform based on the disease pathophysiology may represent a novel therapeutic approach for the disease treatment including cardiovascular diseases.

  2. Soluble guanylate cyclase stimulation prevents fibrotic tissue remodeling and improves survival in salt-sensitive Dahl rats.

    Directory of Open Access Journals (Sweden)

    Sandra Geschka

    Full Text Available BACKGROUND: A direct pharmacological stimulation of soluble guanylate cyclase (sGC is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521, have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. METHODS AND RESULTS: Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 and plasminogen activator inhibitor-1 (PAI-1 in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1. CONCLUSIONS: Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions.

  3. Diabetes Drugs and Cardiovascular Safety

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae

    2016-06-01

    Full Text Available Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

  4. Interactions between remodelling, architecture and tissue properties in cancellous bone

    OpenAIRE

    Linden, Jacqueline

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancellous bone. For this reason, the research presented in this thesis focussed on bone remodeling in cancellous bone. We used computer modeling, finite element calculations and in vivo labeled bone speci...

  5. Cardiovascular Reactivity in Patients With Major Depressive Disorder With High- or Low-Level Depressive Symptoms: A Cross-Sectional Comparison of Cardiovascular Reactivity to Laboratory-Induced Mental Stress.

    Science.gov (United States)

    Wang, Mei-Yeh; Chiu, Chen-Huan; Lee, Hsin-Chien; Su, Chien-Tien; Tsai, Pei-Shan

    2016-03-01

    Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (β = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD.

  6. miRNA therapeutics in cardiovascular diseases: promises and problems

    Directory of Open Access Journals (Sweden)

    Nazila eNouraee

    2015-06-01

    Full Text Available miRNAs are a novel class of non-coding RNAs which found their way into the clinic due to their fundamental roles in cellular processes such as differentiation, proliferation and apoptosis. Recently, miRNAs have been known as micromodulators in cellular communications being involved in cell signaling and microenvironment remodeling. In this review, we will focus on the role of miRNAs in cardiovascular diseases (CVDs and their reliability as diagnostic and therapeutic biomarkers in these conditions. Cardiovascular diseases comprise a variety of blood vessels and heart disorders with a high rate of morbidity and mortality worldwide. This necessitates introduction of novel molecular biomarkers for early detection, prevention or treatment of these diseases. miRNAs, due to their stability, tissue-specific expression pattern and secretion to the corresponding body fluids, are attractive targets for cardiovascular-associated therapeutics. Explaining the challenges ahead of miRNA-based therapies, we will discuss the exosomes as delivery packages for miRNA drugs and promising novel strategies for the future of miRNA-based therapeutics. These approaches provide insights to the future of personalized medicine for the treatment of cardiovascular diseases.

  7. YKL-40 - an emerging biomarker in cardiovascular disease and diabetes

    Directory of Open Access Journals (Sweden)

    Rathcke Camilla

    2009-01-01

    Full Text Available Abstract Several inflammatory cytokines are involved in vascular inflammation resulting in endothelial dysfunction which is the earliest event in the atherosclerotic process leading to manifest cardiovascular disease. YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. YKL-40 protein expression is seen in macrophages and smooth muscle cells in atherosclerotic plaques with the highest expression seen in macrophages in the early lesion of atherosclerosis. Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated with all-cause as well as cardiovascular mortality. Finally, YKL-40 levels are elevated both in patients with type 1 and type 2 diabetes, known to be at high risk for the development of cardiovascular diseases, when compared to non-diabetic persons. A positive association between elevated circulating YKL-40 levels and increasing levels of albuminuria have been described in patients with type 1 diabetes indicating a role of YKL-40 in the progressing vascular damage resulting in microvascular disease. This review describes the present knowledge about YKL-40 and discusses its relation to endothelial dysfunction, atherosclerosis, cardiovascular disease and diabetes and look ahead on future perspectives of YKL-40 research.

  8. Role of Endogenous Sulfur Dioxide in Regulating Vascular Structural Remodeling in Hypertension

    Science.gov (United States)

    Chen, Selena; Tang, Chaoshu

    2016-01-01

    Sulfur dioxide (SO2), an emerging gasotransmitter, was discovered to be endogenously generated in the cardiovascular system. Recently, the physiological effects of endogenous SO2 were confirmed. Vascular structural remodeling (VSR), an important pathological change in many cardiovascular diseases, plays a crucial role in the pathogenesis of the diseases. Here, the authors reviewed the research progress of endogenous SO2 in regulating VSR by searching the relevant data from PubMed and Medline. In spontaneously hypertensive rats (SHRs) and pulmonary hypertensive rats, SO2/aspartate aminotransferase (AAT) pathway was significantly altered. SO2 inhibited vascular smooth muscle cell (VSMC) proliferation, promoted apoptosis, inhibited the synthesis of extracellular collagen but promoted its degradation, and enhanced antioxidative capacity, thereby playing a significant role in attenuating VSR. However, the detailed mechanisms needed to be further explored. Further studies in this field would be important for the better understanding of the pathogenesis of systemic hypertension and pulmonary hypertension. Also, clinical trials are needed to demonstrate if SO2 would be a potential therapeutic target in cardiovascular diseases.

  9. Testosterone deficiency and cardiovascular mortality

    Institute of Scientific and Technical Information of China (English)

    Abraham Morgentaler

    2015-01-01

    New concerns have been raised regarding cardiovascular (CV) risks with testosterone (T) therapy (TTh). These concerns are based primarily on two widely reported retrospective studies. However, methodological flaws and data errors invalidate both studies as credible evidence of risk. One showed reduced adverse events by half in T‑treated men but reversed this result using an unproven statistical approach. The authors subsequently acknowledged serious data errors including nearly 10% contamination of the dataset by women. The second study mistakenly used the rate of T prescriptions written by healthcare providers to men with recent myocardial infarction (MI) as a proxy for the naturally occurring rate of MI. Numerous studies suggest T is beneficial, including decreased mortality in association with TTh, reduced MI rate with TTh in men with the greatest MI risk prognosis, and reduced CV and overall mortality with higher serum levels of endogenous T. Randomized controlled trials have demonstrated benefits of TTh in men with coronary artery disease and congestive heart failure. Improvement in CV risk factors such as fat mass and glycemic control have been repeatedly demonstrated in T‑deficient men treated with T. The current evidence does not support the belief that TTh is associated with increased CV risk or CV mortality. On the contrary, a wealth of evidence accumulated over several decades suggests that low serum T levels are associated with increased risk and that higher endogenous T, as well as TTh itself, appear to be beneficial for CV mortality and risk.

  10. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  11. Phospholipid remodeling and eicosanoid signaling in colon cancer cells.

    Science.gov (United States)

    Das, Siddhartha; Martinez, Leobarda Robles; Ray, Suparna

    2014-12-01

    Phospholipid remodeling and eicosanoid synthesis are central to lipid-based inflammatory reactions. Studies have revealed that membrane phospholipid remodeling by fatty acids through deacylation/reacylation reactions increases the risk of colorectal cancers (CRC) by allowing the cells to produce excess inflammatory eicosanoids, such as prostaglandins, thromboxanes and leukotrienes. Over the years, efforts have been made to understand the lipid remodeling pathways and to design anti-cancer drugs targeting the enzymes of eicosanoid biosynthesis. Here, we discuss the recent progress in phospholipid remodeling and eicosanoid biosynthesis in CRC.

  12. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling......-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope...

  13. Pregnancy-induced remodeling of heart valves.

    Science.gov (United States)

    Pierlot, Caitlin M; Moeller, Andrew D; Lee, J Michael; Wells, Sarah M

    2015-11-01

    Recent studies have demonstrated remodeling of aortic and mitral valves leaflets under the volume loading and cardiac expansion of pregnancy. Those valves' leaflets enlarge with altered collagen fiber architecture, content, and cross-linking and biphasic changes (decreases, then increases) in extensibility during gestation. This study extends our analyses to right-sided valves, with additional compositional measurements for all valves. Valve leaflets were harvested from nonpregnant heifers and pregnant cows. Leaflet structure was characterized by leaflet dimensions, and ECM composition was determined using standard biochemical assays. Histological studies assessed changes in cellular and ECM components. Leaflet mechanical properties were assessed using equibiaxial mechanical testing. Collagen thermal stability and cross-linking were assessed using denaturation and hydrothermal isometric tension tests. Pulmonary and tricuspid leaflet areas increased during pregnancy by 35 and 55%, respectively. Leaflet thickness increased by 20% only in the pulmonary valve and largely in the fibrosa (30% thickening). Collagen crimp length was reduced in both the tricuspid (61%) and pulmonary (42%) valves, with loss of crimped area in the pulmonary valve. Thermomechanics showed decreased collagen thermal stability with surprisingly maintained cross-link maturity. The pulmonary leaflet exhibited the biphasic change in extensibility seen in left side valves, whereas the tricuspid leaflet mechanics remained largely unchanged throughout pregnancy. The tricuspid valve exhibits a remodeling response during pregnancy that is significantly diminished from the other three valves. All valves of the heart remodel in pregnancy in a manner distinct from cardiac pathology, with much similarity valve to valve, but with interesting valve-specific responses in the aortic and tricuspid valves.

  14. Impact of birth weight and early infant weight gain on insulin resistance and associated cardiovascular risk factors in adolescence

    DEFF Research Database (Denmark)

    Fabricius-Bjerre, Signe; Jensen, Rikke Beck; Færch, Kristine;

    2011-01-01

    Low birth weight followed by accelerated weight gain during early childhood has been associated with adverse metabolic and cardiovascular outcomes later in life. The aim of this study was to examine the impact of early infant weight gain on glucose metabolism and cardiovascular risk factors in ad...

  15. Clocks and cardiovascular function

    Science.gov (United States)

    McLoughlin, Sarah C.; Haines, Philip; FitzGerald, Garret A.

    2016-01-01

    Circadian clocks in central and peripheral tissues enable the temporal synchronization and organization of molecular and physiological processes of rhythmic animals, allowing optimum functioning of cells and organisms at the most appropriate time of day. Disruption of circadian rhythms, from external or internal forces, leads to widespread biological disruption and is postulated to underlie many human conditions, such as the incidence and timing of cardiovascular disease. Here, we describe in vivo and in vitro methodology relevant to studying the role of circadian rhythms in cardiovascular function and dysfunction PMID:25707279

  16. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Henriksen, Jens Henrik Sahl

    2008-01-01

    and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed....

  17. Cardiovascular complications of cirrhosis

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2008-01-01

    and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis......Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction....... The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.  ...

  18. Envejecimiento del sistema cardiovascular

    OpenAIRE

    2005-01-01

    Las principales características del envejecimiento del sistema cardiovascular reflejan cambios anatómicos y estructurales a nivel de la pared de los vasos, la relajación miocárdica, el llenado ventricular y la respuesta a las catecolaminas . Muchos de los cambios funcionales asociados con la edad están relacionados con estos fenómenos. Esta revisión describe los cambios relacionados con el envejecimiento a nivel estructural y funcional del sistema cardiovascular, sus posibles factores etiológ...

  19. Pharmacogenomics and cardiovascular disease

    DEFF Research Database (Denmark)

    Weeke, Peter; Roden, Dan M

    2013-01-01

    Variability in drug responsiveness is a sine qua non of modern therapeutics, and the contribution of genomic variation is increasingly recognized. Investigating the genomic basis for variable responses to cardiovascular therapies has been a model for pharmacogenomics in general and has established...... resulted in changes to the product labels but also have led to development of initial clinical guidelines that consider how to facilitate incorporating genetic information to the bedside. This review summarizes the state of knowledge in cardiovascular pharmacogenomics and considers how variants described...

  20. Research in cardiovascular care

    DEFF Research Database (Denmark)

    Jaarsma, Tiny; Deaton, Christi; Fitzsimmons, Donna

    2014-01-01

    To deliver optimal patient care, evidence-based care is advocated and research is needed to support health care staff of all disciplines in deciding which options to use in their daily practice. Due to the increasing complexity of cardiac care across the life span of patients combined...... of the body of knowledge that is needed to further improve cardiovascular care. In this paper, knowledge gaps in current research related to cardiovascular patient care are identified, upcoming challenges are explored and recommendations for future research are given....

  1. Myeloperoxidase and cardiovascular disease.

    Science.gov (United States)

    Nicholls, Stephen J; Hazen, Stanley L

    2005-06-01

    Myeloperoxidase (MPO) is a leukocyte-derived enzyme that catalyzes the formation of a number of reactive oxidant species. In addition to being an integral component of the innate immune response, evidence has emerged that MPO-derived oxidants contribute to tissue damage during inflammation. MPO-catalyzed reactions have been attributed to potentially proatherogenic biological activities throughout the evolution of cardiovascular disease, including during initiation, propagation, and acute complication phases of the atherosclerotic process. As a result, MPO and its downstream inflammatory pathways represent attractive targets for both prognostication and therapeutic intervention in the prophylaxis of atherosclerotic cardiovascular disease.

  2. CHD chromatin remodelers and the transcription cycle.

    Science.gov (United States)

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  3. International Symposium on Cardiovascular Remodeling, Ion channelpathy, Arrhythnnias and Drug Treatment

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    2001 Sept 24 - 26 Nanjing, CHINA Info: Dr DAI De-Zai Professor of Pharmacology Research Division of Pharmacology China Pharmaceutical University Nanjing 210009 CHINA Phn 86-25-327-1270/327-1453 Fax 86-25-330-2827 E-mail njpdaidz @jlonline. com

  4. Adverse responses to local anaesthetics.

    Science.gov (United States)

    Fisher, M M; Graham, R

    1984-11-01

    Progressive challenge was used to investigate twenty-seven patients with a history of an adverse response to local anaesthesia. True allergy was detected in only one patient. The method does not exclude reactions to additives and preservatives in local anaesthetics. If preservative-free local anaesthetics are used for subsequent exposure in patients with no response to progressive challenge, subsequent exposure is safe. The possibility that some of these patients may be reacting to preservatives in the solutions cannot be excluded by such testing. Where possible preservative-free local anaesthetic preparations should be used for subsequent anaesthesia.

  5. Family skills for overcoming adversity

    Directory of Open Access Journals (Sweden)

    Mónica Patricia Ardila Hernández

    2013-12-01

    Full Text Available This section draws on research four families in displacement in Tunja Boyacá step of this research is to present the problem of displacement from another different look that has embargoed regarding this topic. Critical reflection was raised from resilient approach Parsons theory in order to understand families immersed in this conflict as change agents capable of adapting to a new system and overcome adversity. Within this scheme is used to obtain qualitative research of the following categories : adaptation to the new social context risk factors present in families and protective factors.

  6. Pharmacogenetics of cardiovascular drugs.

    Science.gov (United States)

    Johnson, Julie A; Humma, Larisa M

    2002-02-01

    Pharmacogenetics is a field aimed at understanding the genetic contribution to inter-patient variability in drug efficacy and toxicity. Treatment of cardiovascular disease is, in most cases, guided by evidence from well-controlled clinical trials. Given the solid scientific basis for the treatment of most cardiovascular diseases, it is common for patients with a given disease to be treated in essentially the same manner. Thus, the clinical trials have been very informative about treating large groups of patients with a given disease, but are slightly less informative about the treatment of individual patients. Pharmacogenetics and pharmacogenomics have the potential of taking the information derived from large clinical trials and further refining it to select the drugs with the greatest likelihood for benefit, and least likelihood for harm, in individual patients, based on their genetic make-up. In this paper, the current literature on cardiovascular pharmacogenetics is emphasised, and how the use of pharmacogenetic/pharmacogenomic information may be particularly useful in the future in the treatment of cardiovascular diseases is also highlighted.

  7. Cheese and cardiovascular health

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard

    Cardiovascular diseases (CVDs) are the number one cause of mortality worldwide. Low-density lipoprotein (LDL) cholesterol is a well-known risk factor of CVD which increases after the intake of saturated fatty acids (SFA). Cheese is a dietary product commonly consumed in Western countries and known...

  8. Cardiovascular effects of gliptins.

    Science.gov (United States)

    Scheen, André J

    2013-02-01

    Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile.

  9. Neuropeptides in cardiovascular control.

    Science.gov (United States)

    Ganong, W F

    1984-12-01

    Neuropeptides can affect cardiovascular function in various ways. They can serve as cotransmitters in the autonomic nervous system; for example, vasoactive intestinal peptide (VIP) is released with acetylcholine and neuropeptide Y with norepinephrine from postganglionic neurons. Substance P and, presumably, other peptides can can affect cardiovascular function when released near blood vessels by antidromically conducted impulses in branches of stimulated sensory neurons. In the central nervous system, many different neuropeptides appear to function as transmitters or contransmittes in the neural pathways that regulate the cardiovascular system. In addition neuropeptides such as vasopressin and angiotensin II also circulate as hormones that are involved in cardiovascular control. Large doses of exogenous vasopressin are required to increase blood pressure in normal animals because the increase in total peripheral resistance produced by the hormones is accompanied by a decrease in cardiac output. However, studies with synthetic peptides that selectively antagonize the vasopressor action of vasopressin indicate that circulating vasopressin is important in maintaining blood pressure when animals are hypovolemic due to dehydration, haemorrhage or adrenocortical insufficiency. VIP dilates blood vessels and stimulates renin secretion by a direct action on the juxtaglomerular cells. Renin secretion is stimulated when the concentration of VIP in plasma exceeds 75 pmol/litre, and higher values are seen in a number of conditions. Neostigmine, a drug which increases the secretion of endogenous VIP, also increases renin secretion, and this increase is not blocked by renal denervation or propranolol. Thus, VIP may be a physiologically significant renin stimulating hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Epigenetics and cardiovascular disease

    Science.gov (United States)

    Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...

  11. ECG manifestations of left ventricular electrical remodeling.

    Science.gov (United States)

    Estes, E Harvey

    2012-01-01

    Research and thinking about the electrocardiographic manifestations of left ventricular hypertrophy has been constrained by a limited conceptual model of the process: heart disease produces chamber enlargement (increased mass), which in turn produces an altered electrocardiogram. The process is much more complex than can be represented in this simple model. A more robust and intricate model is proposed, in which heart (and vascular) disease causes structural changes, electrical changes, biochemical changes, and others, all of which interact to produce electrical remodeling of ventricular myocardium. This electrical remodeling results in a variety of ECG changes. All of these changes interact, leading to an altered clinical course, and to premature death. It is suggested that research, based on this model, can provide new clues to the processes involved, and improve the prediction of clinical outcomes. New directions in research, in recording equipment, and in organizational activities are suggested to test this new model, and to improve the usefulness of the electrocardiogram as a research and diagnostic tool.

  12. Specific remodeling of splenic architecture by cytomegalovirus.

    Directory of Open Access Journals (Sweden)

    Chris A Benedict

    2006-03-01

    Full Text Available Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21. The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  13. Epithelial Cell Apoptosis and Lung Remodeling

    Institute of Scientific and Technical Information of China (English)

    Kazuyoshi Kuwano

    2007-01-01

    Lung epithelium is the primary site of lung damage in various lung diseases. Epithelial cell apoptosis has been considered to be initial event in various lung diseases. Apoptosis signaling is classically composed of two principle pathways. One is a direct pathway from death receptor ligation to caspase cascade activation and cell death. The other pathway triggered by stresses such as drugs, radiation, infectious agents and reactive oxygen species is mediated by mitochondria. Endoplasmic reticulum has also been shown to be the organelle to mediate apoptosis.Epithelial cell death is followed by remodeling processes, which consist of epithelial and fibroblast activation,cytokine production, activation of coagulation pathway, neoangiogenesis, re-epithelialization and fibrosis.Epithelial and mesenchymal interaction plays important roles in these processes. Further understanding of apoptosis signaling and its regulation by novel strategies may lead to effective treatments against various lung diseases. We review the recent advances in the understanding of apoptosis signaling and discuss the involvement of apoptosis in lung remodeling.

  14. Specific remodeling of splenic architecture by cytomegalovirus.

    Science.gov (United States)

    Benedict, Chris A; De Trez, Carl; Schneider, Kirsten; Ha, Sukwon; Patterson, Ginelle; Ware, Carl F

    2006-03-01

    Efficient immune defenses are facilitated by the organized microarchitecture of lymphoid organs, and this organization is regulated by the compartmentalized expression of lymphoid tissue chemokines. Mouse cytomegalovirus (MCMV) infection induces significant remodeling of splenic microarchitecture, including loss of marginal zone macrophage populations and dissolution of T and B cell compartmentalization. MCMV preferentially infected the splenic stroma, targeting endothelial cells (EC) as revealed using MCMV-expressing green fluorescent protein. MCMV infection caused a specific, but transient transcriptional suppression of secondary lymphoid chemokine (CCL21). The loss of CCL21 was associated with the failure of T lymphocytes to locate within the T cell zone, although trafficking to the spleen was unaltered. Expression of CCL21 in lymphotoxin (LT)-alpha-deficient mice is dramatically reduced, however MCMV infection further reduced CCL21 levels, suggesting that viral modulation of CCL21 was independent of LTalpha signaling. Activation of LTbeta-receptor signaling with an agonistic antibody partially restored CCL21 mRNA expression and redirected transferred T cells to the splenic T cell zone in MCMV-infected mice. These results indicate that virus-induced alterations in lymphoid tissues can occur through an LT-independent modulation of chemokine transcription, and targeting of the LT cytokine system can counteract lymphoid tissue remodeling by MCMV.

  15. Vascular remodeling underlies rebleeding in hemophilic arthropathy.

    Science.gov (United States)

    Bhat, Vikas; Olmer, Merissa; Joshi, Shweta; Durden, Donald L; Cramer, Thomas J; Barnes, Richard Fw; Ball, Scott T; Hughes, Tudor H; Silva, Mauricio; Luck, James V; Moore, Randy E; Mosnier, Laurent O; von Drygalski, Annette

    2015-11-01

    Hemophilic arthropathy is a debilitating condition that can develop as a consequence of frequent joint bleeding despite adequate clotting factor replacement. The mechanisms leading to repeated spontaneous bleeding are unknown. We investigated synovial, vascular, stromal, and cartilage changes in response to a single induced hemarthrosis in the FVIII-deficient mouse. We found soft-tissue hyperproliferation with marked induction of neoangiogenesis and evolving abnormal vascular architecture. While soft-tissue changes were rapidly reversible, abnormal vascularity persisted for months and, surprisingly, was also seen in uninjured joints. Vascular changes in FVIII-deficient mice involved pronounced remodeling with expression of α-Smooth Muscle Actin (SMA), Endoglin (CD105), and vascular endothelial growth factor, as well as alterations of joint perfusion as determined by in vivo imaging. Vascular architecture changes and pronounced expression of α-SMA appeared unique to hemophilia, as these were not found in joint tissue obtained from mouse models of rheumatoid arthritis and osteoarthritis and from patients with the same conditions. Evidence that vascular changes in hemophilia were significantly associated with bleeding and joint deterioration was obtained prospectively by dynamic in vivo imaging with musculoskeletal ultrasound and power Doppler of 156 joints (elbows, knees, and ankles) in a cohort of 26 patients with hemophilia at baseline and during painful episodes. These observations support the hypothesis that vascular remodeling contributes significantly to bleed propagation and development of hemophilic arthropathy. Based on these findings, the development of molecular targets for angiogenesis inhibition may be considered in this disease.

  16. 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.

  17. The Cardiovascular Research Grid (CVRG)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CardioVascular Research Grid (CVRG) project is creating an infrastructure for sharing cardiovascular data and data analysis tools. CVRG tools are developed using...

  18. Nonfasting hyperlipidemia and cardiovascular disease

    DEFF Research Database (Denmark)

    Nordestgaard, B G; Langsted, A; Freiberg, J J

    2009-01-01

    , total cholesterol/HDL cholesterol, and apolipoprotein B/apolipoprotein A1 all associate with increased risk of cardiovascular disease. These new data open the possibility that nonfasting rather than fasting lipid profiles can be used for cardiovascular risk prediction. If implemented, this would...... of cardiovascular disease and early death....

  19. CDC Wonder Vaccine Adverse Event Reporting System

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Vaccine Adverse Event Reporting System (VAERS) online database on CDC WONDER provides counts and percentages of adverse event case reports after vaccination,...

  20. "Adversative Conjunction": The Poetics of Linguistic Opposition.

    Science.gov (United States)

    Wallerstein, Nicholas

    1992-01-01

    The general use of adversative conjunction in (primarily) English and U.S. poetry is outlined. The contention is that the adversative is not merely a grammatical convenience but sometimes a highly functional tool of rhetorical strategy. (36 references) (LB)

  1. Galectin-3 and post-myocardial infarction cardiac remodeling

    NARCIS (Netherlands)

    Meijers, Wouter C.; van der Velde, A. Rogier; Pascual-Figal, Domingo A.; de Boer, Rudolf A.

    2015-01-01

    This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling. Post-myocardial infarction remodeling is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in

  2. Interactions between remodelling, architecture and tissue properties in cancellous bone

    NARCIS (Netherlands)

    J.C. van der Linden (Jacqueline)

    2003-01-01

    textabstractThe aim of the research projects described in this thesis was to gain more insight in the regulation of bone remodeling and in the interactions between bone remodeling, architecture and bone tissue properties. The most striking changes during aging and osteoporosis take place in cancello

  3. The behavior of adaptive bone-remodeling simulation models

    NARCIS (Netherlands)

    H.H. Weinans (Harrie); R. Huiskes (Rik); H.J. Grootenboer

    1992-01-01

    textabstractThe process of adaptive bone remodeling can be described mathematically and simulated in a computer model, integrated with the finite element method. In the model discussed here, cortical and trabecular bone are described as continuous materials with variable density. The remodeling rule

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Effects of Growth Hormone on Cardiac Remodeling During Resistance Training in Rats

    Energy Technology Data Exchange (ETDEWEB)

    Junqueira, Adriana, E-mail: francispacagnelli@unoeste.br [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Cicogna, Antônio Carlos [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Engel, Letícia Estevam; Aldá, Maiara Almeida [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Tomasi, Loreta Casquel de [Universidade Estadual Paulista (UNESP), Campus Botucatu, SP (Brazil); Giuffrida, Rogério; Giometti, Inês Cristina [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Freire, Ana Paula Coelho Figueira [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil); Universidade Estadual Paulista (UNESP), Campus Presidente Prudente, SP (Brazil); Aguiar, Andreo Fernando [Universidade do Norte do Paraná, UNOPAR, Londrina, PR (Brazil); Pacagnelli, Francis Lopes [Universidade do Oeste Paulista (UNOESTE), Presidente Prudente, SP (Brazil)

    2016-01-15

    Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program. To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT. Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR). There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH). GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca{sup 2+} transport.

  6. Vessel remodelling, pregnancy hormones and extravillous trophoblast function.

    Science.gov (United States)

    Chen, Jessie Z-J; Sheehan, Penelope M; Brennecke, Shaun P; Keogh, Rosemary J

    2012-02-26

    During early human pregnancy, extravillous trophoblast (EVT) cells from the placenta invade the uterine decidual spiral arterioles and mediate the remodelling of these vessels such that a low pressure, high blood flow can be supplied to the placenta. This is essential to facilitate normal growth and development of the foetus. Defects in remodelling can manifest as the serious pregnancy complication pre-eclampsia. During the period of vessel remodelling three key pregnancy-associated hormones, human chorionic gonadotrophin (hCG), progesterone (P(4)) and oestradiol (E(2)), are found in high concentrations at the maternal-foetal interface. Potentially these hormones may control EVT movement and thus act as regulators of vessel remodelling. This review will discuss what is known about how these hormones affect EVT proliferation, migration and invasion during vascular remodelling and the potential relationship between hCG, P(4), E(2) and the development of pre-eclampsia.

  7. The redox state of transglutaminase 2 controls arterial remodeling

    DEFF Research Database (Denmark)

    van den Akker, Jeroen; VanBavel, Ed; van Geel, Remon

    2011-01-01

    While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates......, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG......2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited...

  8. Mind the gap: predicting cardiovascular risk during drug development

    OpenAIRE

    Chain, Anne S Y

    2012-01-01

    Cardiovascular safety issues, specifically drug-induced QT/QTc-interval prolongation, remain a major cause of drug attrition during clinical development and is one of the main causes for post-market drug withdrawals accounting for 15-34% of all drug discontinuation. Given the potentially fatal consequences of this concentration-dependent adverse drug reaction, regulatory authorities have reacted to this “pharmacoepidemic” by denying or delaying the approval of a number of new drugs and placin...

  9. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

    Directory of Open Access Journals (Sweden)

    Mengge Sun

    2016-01-01

    Full Text Available MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  10. The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling

    Directory of Open Access Journals (Sweden)

    Maricica Pacurari

    2014-01-01

    Full Text Available The RAAS through its physiological effectors plays a key role in promoting and maintaining inflammation. Inflammation is an important mechanism in the development and progression of CVD such as hypertension and atherosclerosis. In addition to its main role in regulating blood pressure and its role in hypertension, RAAS has proinflammatory and profibrotic effects at cellular and molecular levels. Blocking RAAS provides beneficial effects for the treatment of cardiovascular and renal diseases. Evidence shows that inhibition of RAAS positively influences vascular remodeling thus improving CVD outcomes. The beneficial vascular effects of RAAS inhibition are likely due to decreasing vascular inflammation, oxidative stress, endothelial dysfunction, and positive effects on regeneration of endothelial progenitor cells. Inflammatory factors such as ICAM-1, VCAM-1, TNFα, IL-6, and CRP have key roles in mediating vascular inflammation and blocking RAAS negatively modulates the levels of these inflammatory molecules. Some of these inflammatory markers are clinically associated with CVD events. More studies are required to establish long-term effects of RAAS inhibition on vascular inflammation, vascular cells regeneration, and CVD clinical outcomes. This review presents important information on RAAS’s role on vascular inflammation, vascular cells responses to RAAS, and inhibition of RAAS signaling in the context of vascular inflammation, vascular remodeling, and vascular inflammation-associated CVD. Nevertheless, the review also equates the need to rethink and rediscover new RAAS inhibitors.

  11. Childhood obesity and cardiac remodeling: from cardiac structure to myocardial mechanics.

    Science.gov (United States)

    Tadic, Marijana; Cuspidi, Cesare

    2015-08-01

    Epidemic of obesity, especially morbid obesity, among children and adolescents, is a key factor associated with the dramatic increase in prevalence of type 2 diabetes mellitus, arterial hypertension, and metabolic syndrome in this population. Furthermore, childhood obesity represents a very important predictor of obesity in adulthood that is related to cardiovascular and cerebrovascular diseases. Overweight and obesity in children and adolescents are associated with impairment of cardiac structure and function. The majority of studies investigated the influence of obesity on left ventricular remodeling. However, the impact of obesity on the right ventricle, both the atria, and myocardial mechanics has been insufficiently studied. The aim of this review article is to summarize all data about heart remodeling in childhood, from cardiac size, throughout systolic and diastolic function, to myocardial mechanics, using a wide range of mainly echocardiographic techniques and parameters. Additionally, we sought to present current knowledge about the influence of weight loss, achieved by various therapeutic approaches, on the improvement of cardiac geometry, structure, and function in obese children and adolescents.

  12. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis.

    Science.gov (United States)

    Sun, Mengge; Zhou, Xiaoya; Chen, Lili; Huang, Shishu; Leung, Victor; Wu, Nan; Pan, Haobo; Zhen, Wanxin; Lu, William; Peng, Songlin

    2016-01-01

    MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  13. State of integral remodeling parameters of target organs in patients with essential hypertension and obesity.

    Science.gov (United States)

    Kochueva, M; Sukhonos, V; Shalimova, A; Psareva, V; Kirichenko, N

    2014-06-01

    Arterial hypertension combined with obesity is a very common form of comorbid disease in most countries all over the world. The combination of these diseases is characterized by mutual burdening of remodelling processes in important target organs, what greatly increases the risk of cardiovascular complications and death. The mechanisms of injury progression to vital organs in essential hypertension (EH) and obesity have some common features. The most important risk factors of target organs damage are hemodynamic and neurohumoral: inflammatory, effectors of the renin- angiotensin-aldosterone system, insulin resistance and others. Polyethiologic remodelling, lack of knowledge concerning violations in structural and functional status of important target organs and mechanisms of the interactions of their progression with this comorbidity require further study of these issues. The objective of the study was the comparative study of the state of integral indicators of structural and functional state of the heart, blood vessels and liver in patients with EH second stage with normal body weight and with concomitant obesity I and II degrees. This study found that the presence of obesity I and II in patients with EH stage II is associated with the concentric type of left ventricular hypertrophy, saved by its ejection fraction and impaired diastolic filling processes. For the patients with EH in the early stages of obesity the following characteristics are quite typical: considerable increase of intima media thickness in the carotid arteries, increasing the stiffness in the main arteries and liver parenchyma, impaired of the functional state of endothelial.

  14. Optimal Contracting under Adverse Selection

    DEFF Research Database (Denmark)

    Lenells, Jonatan; Stea, Diego; Foss, Nicolai Juul

    2015-01-01

    We study a model of adverse selection, hard and soft information, and mentalizing ability--the human capacity to represent others' intentions, knowledge, and beliefs. By allowing for a continuous range of different information types, as well as for different means of acquiring information, we dev...... of that information. This strategy affects the properties of the optimal contract, which grows closer to the first best. This research provides insights into the implications of mentalizing for agency theory....... develop a model that captures how principals differentially obtain information on agents. We show that principals that combine conventional data collection techniques with mentalizing benefit from a synergistic effect that impacts both the amount of information that is accessed and the overall cost...

  15. Adverse reactions to drug additives.

    Science.gov (United States)

    Simon, R A

    1984-10-01

    There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.

  16. Relation of serum uric acid to cardiovascular disease.

    Science.gov (United States)

    Wu, Audrey H; Gladden, James D; Ahmed, Mustafa; Ahmed, Ali; Filippatos, Gerasimos

    2016-06-15

    This review summarizes recent published literature on the association between serum uric acid and cardiovascular disease, a relationship which is complex and not fully elucidated. Uric acid may be a marker for risk, a causative agent in cardiovascular disease, or both. Various biologic factors can influence serum uric acid levels, and serum uric acid level itself is closely related to conditions such as hypertension, dyslipidemia, obesity, and impaired glucose metabolism, that contribute to cardiovascular disease pathophysiology. Serum uric acid levels have been found to be associated with adverse outcomes, including mortality, in the general population. In addition, serum uric acid is associated with increased risk for incident coronary heart disease, heart failure, and atrial fibrillation. In the setting of established systolic heart failure, serum uric acid is positively associated with disease severity and mortality risk. Whether targeting treatment based on uric acid levels might affect clinical outcomes is still being studied.

  17. Cardiovascular Considerations in Antidepressant Therapy: An Evidence-Based Review

    Directory of Open Access Journals (Sweden)

    Habibeh Yekehtaz

    2015-10-01

    Full Text Available There is a definite correlation between cardiovascular diseases and depressive disorders. Nevertheless, many aspects of this association have yet to be fully elucidated. Up to half of coronary artery disease patients are liable to suffer from some depressive symptoms, with approximately 20% receiving a diagnosis of major depressive disorders. Pharmacotherapy is a key factor in the management of major depression, not least in patients with chronic diseases who are likely to fail to show proper compliance and response to non-pharmacological interventions. Antidepressants are not deemed completely safe. Indeed, numerous side effects have been reported with the administration of antidepressants, among which cardiovascular adverse events are of paramount importance owing to their disabling and life-threatening nature. We aimed to re-examine some of the salient issues in antidepressant therapy vis-à-vis cardiovascular considerations, which should be taken into account when prescribing such medications.

  18. Anti-remodeling effects of rapamycin in experimental heart failure: dose response and interaction with angiotensin receptor blockade.

    Science.gov (United States)

    Bishu, Kalkidan; Ogut, Ozgur; Kushwaha, Sudhir; Mohammed, Selma F; Ohtani, Tomohito; Xu, Xiaolei; Brozovich, Frank V; Redfield, Margaret M

    2013-01-01

    While neurohumoral antagonists improve outcomes in heart failure (HF), cardiac remodeling and dysfunction progress and outcomes remain poor. Therapies superior or additive to standard HF therapy are needed. Pharmacologic mTOR inhibition by rapamycin attenuated adverse cardiac remodeling and dysfunction in experimental heart failure (HF). However, these studies used rapamycin doses that produced blood drug levels targeted for primary immunosuppression in human transplantation and therefore the immunosuppressive effects may limit clinical translation. Further, the relative or incremental effect of rapamycin combined with standard HF therapies targeting upstream regulators of cardiac remodeling (neurohumoral antagonists) has not been defined. Our objectives were to determine if anti-remodeling effects of rapamycin were preserved at lower doses and whether rapamycin effects were similar or additive to a standard HF therapy (angiotensin receptor blocker (losartan)). Experimental murine HF was produced by transverse aortic constriction (TAC). At three weeks post-TAC, male mice with established HF were treated with placebo, rapamycin at a dose producing immunosuppressive drug levels (target dose), low dose (50% target dose) rapamycin, losartan or rapamycin + losartan for six weeks. Cardiac structure and function (echocardiography, catheterization, pathology, hypertrophic and fibrotic gene expression profiles) were assessed. Downstream mTOR signaling pathways regulating protein synthesis (S6K1 and S6) and autophagy (LC3B-II) were characterized. TAC-HF mice displayed eccentric hypertrophy, systolic dysfunction and pulmonary congestion. These perturbations were attenuated to a similar degree by oral rapamycin doses achieving target (13.3±2.1 ng/dL) or low (6.7±2.5 ng/dL) blood levels. Rapamycin treatment decreased mTOR mediated regulators of protein synthesis and increased mTOR mediated regulators of autophagy. Losartan monotherapy did not attenuate remodeling, whereas

  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. Chondromodulin I Is a Bone Remodeling Factor

    Science.gov (United States)

    Nakamichi, Yuko; Shukunami, Chisa; Yamada, Takashi; Aihara, Ken-ichi; Kawano, Hirotaka; Sato, Takashi; Nishizaki, Yuriko; Yamamoto, Yoko; Shindo, Masayo; Yoshimura, Kimihiro; Nakamura, Takashi; Takahashi, Naoyuki; Kawaguchi, Hiroshi; Hiraki, Yuji; Kato, Shigeaki

    2003-01-01

    Chondromodulin I (ChM-I) was supposed from its limited expression in cartilage and its functions in cultured chondrocytes as a major regulator in cartilage development. Here, we generated mice deficient in ChM-I by targeted disruption of the ChM-I gene. No overt abnormality was detected in endochondral bone formation during embryogenesis and cartilage development during growth stages of ChM-I−/− mice. However, a significant increase in bone mineral density with lowered bone resorption with respect to formation was unexpectedly found in adult ChM-I−/− mice. Thus, the present study established that ChM-I is a bone remodeling factor. PMID:12509461

  1. Multiscale Bone Remodelling with Spatial P Systems

    CERN Document Server

    Cacciagrano, Diletta; Merelli, Emanuela; Tesei, Luca; 10.4204/EPTCS.40.6

    2010-01-01

    Many biological phenomena are inherently multiscale, i.e. they are characterized by interactions involving different spatial and temporal scales simultaneously. Though several approaches have been proposed to provide "multilayer" models, only Complex Automata, derived from Cellular Automata, naturally embed spatial information and realize multiscaling with well-established inter-scale integration schemas. Spatial P systems, a variant of P systems in which a more geometric concept of space has been added, have several characteristics in common with Cellular Automata. We propose such a formalism as a basis to rephrase the Complex Automata multiscaling approach and, in this perspective, provide a 2-scale Spatial P system describing bone remodelling. The proposed model not only results to be highly faithful and expressive in a multiscale scenario, but also highlights the need of a deep and formal expressiveness study involving Complex Automata, Spatial P systems and other promising multiscale approaches, such as ...

  2. [Multiculturalism and cardiovascular diseases].

    Science.gov (United States)

    Gaudio, Carlo; Corsi, Filippo; Esposito, Cosimo; Di Michele, Sara; Nguyen, Bich Lien; Khatibi, Shahrzad; Sciarretta, Tesir; Franchitto, Silvia; Mirabelli, Francesca; Pannarale, Giuseppe

    2004-01-01

    Immigration has increased drastically to the point of becoming an ordinary structure of our society. Once in Italy, the immigrant's health is compromised rapidly due to a series of conditions and illnesses that exist in our country: lack of work, inadequate salary, inappropriate residence, lacking family support, climate changes, nutritional differences. Cardiovascular illnesses represent 7.6% of the diseases of the immigrants, and cause 36.6% of deaths. The risk factors that affect the genesis of cardiovascular diseases include: subjective factors (age, ethnic group), environmental, nutritional and pathological (arterial hypertension, AIDS, tuberculosis, alcohol). The challenge for our time is to design a new solidarity model to promote cultural and social integration in order to meet the multiethnical and multiracial needs of western society. This model should permit reconsideration of doctor-patient relationship in order to build a real intercultural society.

  3. Migraine and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Marcelo E. Bigal

    2011-02-01

    Full Text Available Migraine, especially migraine with aura is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine with and without aura to a broader range of ischemic vascular disorders including angina, myocardial infarction, coronary revascularization, claudication and cardiovascular mortality. The topic is therefore of considerable interest. Accordingly, herein we review the association between migraine and cardiovascular disease. We start by briefly presenting diagnostic criteria for migraine and revising its pathophysiology. We follow by summarizing the evidence on the topic. We then briefly present the results of a recent meta-analysis. We close by highlighting results of a large epidemiological study conducted after the publication of the meta-analysis.

  4. Prodrugs in Cardiovascular Therapy

    Directory of Open Access Journals (Sweden)

    Maryam Tabrizian

    2008-05-01

    Full Text Available Prodrugs are biologically inactive derivatives of an active drug intended to solve certain problems of the parent drug such as toxicity, instability, minimal solubility and non-targeting capabilities. The majority of drugs for cardiovascular diseases undergo firstpass metabolism, resulting in drug inactivation and generation of toxic metabolites, which makes them appealing targets for prodrug design. Since prodrugs undergo a chemical reaction to form the parent drug once inside the body, this makes them very effective in controlling the release of a variety of compounds to the targeted site. This review will provide the reader with an insight on the latest developments of prodrugs that are available for treating a variety of cardiovascular diseases. In addition, we will focus on several drug delivery methodologies that have merged with the prodrug approach to provide enhanced target specificity and controlled drug release with minimal side effects.

  5. Slow breathing and cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ashish Chaddha

    2015-01-01

    Full Text Available Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

  6. Slow breathing and cardiovascular disease.

    Science.gov (United States)

    Chaddha, Ashish

    2015-01-01

    Cardiovascular disease is the leading cause of death for both men and women worldwide. Much emphasis has been placed on the primary and secondary prevention of cardiovascular disease. While depression and anxiety increase the risk of developing cardiovascular disease, cardiovascular disease also increases the risk of developing anxiety and depression. Thus, promoting optimal mental health may be important for both primary and secondary prevention of cardiovascular disease. Like lowering blood pressure, lipids, and body weight, lowering anger and hostility and improving depression and anxiety may also be an important intervention in preventive cardiology. As we strive to further improve cardiovascular outcomes, the next bridge to cross may be one of offering patients nonpharmacologic means for combating daily mental stress and promoting mental health, such as yoga and pranayama. Indeed, the best preventive cardiovascular medicine may be a blend of both Western and Eastern medicine.

  7. Aldosterone does not predict cardiovascular events following acute coronary syndrome in patients initially without heart failure

    OpenAIRE

    Pitts, Reynaria; Gunzburger, Elise; Ballantyne, Christie M.; Barter, Philip J.; Kallend, David; Leiter, Lawrence A.; Leitersdorf, Eran; Nicholls, Stephen J.; Prediman K Shah; Tardif, Jean-Claude; Olsson, Anders G.; McMurray, John J.V.; Kittelson, John; Schwartz, Gregory G.

    2017-01-01

    Background: Aldosterone may have adverse effects in the myocardium and vasculature. Treatment with an aldosterone antagonist reduces cardiovascular risk in patients with acute myocardial infarction complicated by heart failure (HF) and left ventricular systolic dysfunction. However, most patients with acute coronary syndrome do not have advanced HF. Among such patients, it is unknown whether aldosterone predicts cardiovascular risk.\\ud \\ud Methods and Results: To address this question, we exa...

  8. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts

    OpenAIRE

    Kemi, Ole J.; Hoydal, Morten A; MacQuaide, Niall; Haram, Per M; Koch, Lauren G.; Steven L Britton; Ellingsen, Oyvind; Smith, Godfrey L.; Wisloff, Ulrik

    2011-01-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T-tubule density. Thus, the T-tubules adapted to the physiologi...

  9. Generic versus brand-name drugs used in cardiovascular diseases.

    Science.gov (United States)

    Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A

    2016-04-01

    This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider

  10. Cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Graversen, Peter; Abildstrøm, Steen Z; Jespersen, Lasse

    2016-01-01

    (ECG) abnormalities, heart rate, family history (of ischaemic heart disease), body mass index (BMI), waist-hip ratio, walking duration and pace, leisure time physical activity, forced expiratory volume (FEV)1%pred, household income, education, vital exhaustion, high-density lipoprotein (HDL......AIM: European society of cardiology (ESC) guidelines recommend that cardiovascular disease (CVD) risk stratification in asymptomatic individuals is based on the Systematic Coronary Risk Evaluation (SCORE) algorithm, which estimates individual 10-year risk of death from CVD. We assessed...

  11. The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts.

    Science.gov (United States)

    Kemi, Ole J; Hoydal, Morten A; Macquaide, Niall; Haram, Per M; Koch, Lauren G; Britton, Steven L; Ellingsen, Oyvind; Smith, Godfrey L; Wisloff, Ulrik

    2011-09-01

    The response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P hypertrophy. Next, we studied T-tubules in a rat model of metabolic syndrome with pressure overload-induced concentric left ventricle hypertrophy, evidenced by 15% (P Exercise training further increased cardiomyocyte volume by 8% (P eccentric and concentric hypertrophy and 55% (P Exercise training reversed 50% (P hypertrophy, whereas the T-tubule density increased by 40% (P hypertrophy associated with conserved T-tubule spacing (~1.8-1.9 µm), whereas in pathologic hypertrophy, T-tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T-tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T-tubules; exercise training reverses the remodeling and partly corrects the T-tubule density.

  12. Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes.

    Science.gov (United States)

    Brea, Roberto J; Rudd, Andrew K; Devaraj, Neal K

    2016-08-02

    Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

  13. 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.

  14. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome

    OpenAIRE

    Parihar, Anuj Singh; Katoch, Vartika; Rajguru, Sneha A; Rajpoot, Nami; Singh, Pinojj; Wakhle, Sonal

    2015-01-01

    Bacterial invasion in subgingival sites especially of gram-negative organisms are initiators for periodontal diseases. The periodontal pathogens with persistent inflammation lead to destruction of periodontium. In recent years, periodontal diseases have been associated with a number of systemic diseases such as rheumatoid arthritis, cardiovascular-disease, diabetes mellitus, chronic respiratory diseases and adverse pregnancy outcomes including pre-term low-birth weight (PLBW) and pre-eclampsi...

  15. Adverse effects of antihypertensive drugs.

    Science.gov (United States)

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  16. Stress, Health Behavior, and Sleep as Mediators of the Association between Loneliness and Adverse Health Conditions among Older People

    DEFF Research Database (Denmark)

    Christiansen, Julie

    was significantly associated with poor self-rated health, cardiovascular disease, diabetes, and migraine. In addition, high perceived stress, physical inactivity, problems with alcohol, and poor sleep demonstrated an indirect effect on the association between loneliness and adverse health conditions. The findings...

  17. Super-enhancer lncs to cardiovascular development and disease.

    Science.gov (United States)

    Ounzain, Samir; Pedrazzini, Thierry

    2016-07-01

    Cardiac development, function and pathological remodelling in response to stress depend on the dynamic control of tissue specific gene expression by distant acting transcriptional enhancers. Recently, super-enhancers (SEs), also known as stretch or large enhancer clusters, are emerging as sentinel regulators within the gene regulatory networks that underpin cellular functions. It is becoming increasingly evident that long noncoding RNAs (lncRNAs) associated with these sequences play fundamental roles for enhancer activity and the regulation of the gene programs hardwired by them. Here, we review this emerging landscape, focusing on the roles of SEs and their derived lncRNAs in cardiovascular development and disease. We propose that exploration of this genomic landscape could provide novel therapeutic targets and approaches for the amelioration of cardiovascular disease. Ultimately we envisage a future of ncRNA therapeutics targeting the SE landscape to alleviate cardiovascular disease. 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.

  18. 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.

  19. Pioglitazone alleviates cardiac and vascular remodelling and improves survival in monocrotaline induced pulmonary arterial hypertension.

    Science.gov (United States)

    Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren

    2016-04-01

    Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

  20. Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

    Science.gov (United States)

    Fu, Xuebin; Segiser, Adrian; Carrel, Thierry P.; Tevaearai Stahel, Hendrik T.; Most, Henriette

    2016-01-01

    Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients.

  1. Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction.

    Science.gov (United States)

    Kuznetsova, Tatiana; Haddad, Francois; Knez, Judita; Rosenberg-Hasson, Yael; Sung, Janine; Cauwenberghs, Nicholas; Thijs, Lutgarde; Karakikes, Ioannis; Maecker, Holden; Mahaffey, Kenneth W; Wu, Joseph C; Staessen, Jan A

    2015-12-01

    There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients with HTN in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome. We identified three groups of participants from the cohort: normotensive subjects (normotension; n = 30), HTN with normal LV structure and function (HTN [LV-]; n = 30), and HTN with evidence of adverse LV remodeling (HTN [LV+]; n = 50). We measured cytokines using a 63-plex Luminex platform. Using partial least squares-discriminant analysis, we constructed three latent variables from the measured cytokines that explained 35%-45% of the variance between groups. We identified five common cytokines (interleukin 18, monokine induced by gamma interferon, hepatocyte growth factor, epithelial neutrophil-activating peptide 78, and vascular endothelial growth factor D) with a stable signal which had a major impact on the construction of the latent variables. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P = .02). Moreover, granulocyte-macrophage colony-stimulating factor and leptin showed a consistent upward trend in all HTN patients compared with normotensive subjects. In conclusion, in HTN patients with LV remodeling or/and dysfunction, we identified a set of cytokines strongly associated with LV maladaptation. We also found a distinct profile of inflammatory biomarkers that characterize HTN.

  2. Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis

    DEFF Research Database (Denmark)

    Wu, Jashin J; Strober, Bruce E; Hansen, Peter R;

    2016-01-01

    BACKGROUND: Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. OBJECTIVE: We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV even...

  3. EFECTOS DE LOS MEDICAMENTOS CARDIOVASCULARES SOBRE EL GLOBO OCULAR / Effects of cardiovascular drugs on the eyeball

    Directory of Open Access Journals (Sweden)

    Caridad Peraza Martínez

    2013-01-01

    ophthalmology offices, and many of drugs used for these conditions may cause undesirable effects on the eyeball. The objective of this research was to determine the adverse reactions caused by the consumption of these drugs in the visual organ, and highlight their contraindications in people affected by eye disease. Method: A literature search was performed using specialized texts, and the drugs that could produce ocular adverse reactions were identified, as well as those that were contraindicated in ophthalmic diseases. Results: A total of 276 medications were reviewed and 72 (26.08% were selected. Blurred vision (38/72, decreased visual acuity (21/72 and dizziness (16/72 were the most common adverse reactions associated with the use of cardiovascular drugs. The six medications that are contraindicated in these patients are exposed, as well as the 14 that should be prescribed with extreme caution in diseases such as glaucoma, optic atrophy, hypertensive retinopathy and migraine, among others. Conclusions: It was found that 72 drugs (26.08% used in cardiovascular disease may produce some ocular symptoms as an adverse reaction. Blurred vision, decreased visual acuity and dizziness were predominant. It is extremely important to conduct a good medical interview to know the patient´s medical history and avoid the use of drugs that are useful for a disease but harmful for another one. The doctor, knowingly, will weigh the risk / benefit of those drugs that are essential.

  4. Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence.

    Science.gov (United States)

    Chida, Yoichi; Steptoe, Andrew

    2010-04-01

    An increasing number of studies has tested whether greater cardiovascular responses to acute mental stress predict future cardiovascular disease, but results have been variable. This review aimed quantitatively to evaluate the association between cardiovascular responses to laboratory mental stress and subsequent cardiovascular risk status in prospective cohort studies. We searched general bibliographic databases, PsycINFO, Web of Science, and PubMed, up to December 2009. Two reviewers independently extracted data on study characteristics, quality, and estimates of associations. There were 169 associations (36 articles) of stress reactivity and 30 associations (5 articles) of poststress recovery in relation to future cardiovascular risk status, including elevated blood pressure, hypertension, left ventricular mass, subclinical atherosclerosis, and clinical cardiac events. The overall meta-analyses showed that greater reactivity to and poor recovery from stress were associated longitudinally with poor cardiovascular status (r=0.091 [95% CI: 0.050 to 0.132], Pstress reactivity and poor stress recovery, respectively, whereas both factors were associated with higher future systolic and diastolic blood pressures. In conclusion, the current meta-analysis suggests that greater responsivity to acute mental stress has an adverse effect on future cardiovascular risk status, supporting the use of methods of managing stress responsivity in the prevention and treatment of cardiovascular disease.

  5. The adverse effects of air pollution on the nervous system.

    Science.gov (United States)

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health.

  6. The Adverse Effects of Air Pollution on the Nervous System

    Directory of Open Access Journals (Sweden)

    Sermin Genc

    2012-01-01

    Full Text Available Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS, including stroke, Alzheimer’s disease, Parkinson’s disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health.

  7. Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study

    DEFF Research Database (Denmark)

    Ahlehoff, Ole; Gislason, Gunnar Hilmar; Charlot, Mette Gitz;

    2011-01-01

    Objective. The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality. Design, setting and subjects. We conducted a cohort study of the entire Danish population aged...... with psoriasis and psoriatic arthritis. Main outcome measures. All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded. Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including...... 607 with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients...

  8. Psoriasis is associated with clinically significant cardiovascular risk: a Danish nationwide cohort study

    DEFF Research Database (Denmark)

    Ahlehoff, O; Gislason, G H; Charlot, M;

    2011-01-01

    . The magnitude of the cardiovascular risk from psoriasis and psoriatic arthritis is debated. We therefore investigated the psoriasis-related risk of adverse cardiovascular events and mortality. Design, setting and subjects. We conducted a cohort study of the entire Danish population aged =18 years followed from...... and psoriatic arthritis. Main outcome measures. All-cause mortality, cardiovascular mortality and hospitalizations for myocardial infarction (MI), stroke and coronary revascularization were recorded. Results. A total of 34 371 patients with mild psoriasis and 2621 with severe psoriasis, including 607...... with psoriatic arthritis, were identified and compared with 4 003 265 controls. The event rates and rate ratios (RRs) of all-cause mortality, cardiovascular death, MI, coronary revascularization, stroke and a composite of MI, stroke and cardiovascular death were increased in patients with psoriasis. The rate...

  9. Cardiovascular pharmacogenetics in the SNP era.

    Science.gov (United States)

    Mooser, V; Waterworth, D M; Isenhour, T; Middleton, L

    2003-07-01

    In the past pharmacological agents have contributed to a significant reduction in age-adjusted incidence of cardiovascular events. However, not all patients treated with these agents respond favorably, and some individuals may develop side-effects. With aging of the population and the growing prevalence of cardiovascular risk factors worldwide, it is expected that the demand for cardiovascular drugs will increase in the future. Accordingly, there is a growing need to identify the 'good' responders as well as the persons at risk for developing adverse events. Evidence is accumulating to indicate that responses to drugs are at least partly under genetic control. As such, pharmacogenetics - the study of variability in drug responses attributed to hereditary factors in different populations - may significantly assist in providing answers toward meeting this challenge. Pharmacogenetics mostly relies on associations between a specific genetic marker like single nucleotide polymorphisms (SNPs), either alone or arranged in a specific linear order on a certain chromosomal region (haplotypes), and a particular response to drugs. Numerous associations have been reported between selected genotypes and specific responses to cardiovascular drugs. Recently, for instance, associations have been reported between specific alleles of the apoE gene and the lipid-lowering response to statins, or the lipid-elevating effect of isotretinoin. Thus far, these types of studies have been mostly limited to a priori selected candidate genes due to restricted genotyping and analytical capacities. Thanks to the large number of SNPs now available in the public domain through the SNP Consortium and the newly developed technologies (high throughput genotyping, bioinformatics software), it is now possible to interrogate more than 200,000 SNPs distributed over the entire human genome. One pharmacogenetic study using this approach has been launched by GlaxoSmithKline to identify the approximately 4% of

  10. Omega-3 Fatty Acid Attenuates Cardiovascular Effects in Healthy Older Volunteers Exposed to Concentrated Ambient Fine and UltrafineParticulate Matter

    Science.gov (United States)

    Rationale: Ambient particulate matter (PM) exposure has been associated with adverse cardiovascular effects. A recent epidemiology study reported that omega-3 polyunsaturated fatty acid (fish oil) supplementation blunted the response of study participants to PM. Our study was des...

  11. Scar prevention and remodeling: a review of the medical, surgical, topical and light treatment approaches.

    Science.gov (United States)

    Kerwin, Leonard Y; El Tal, Abdel Kader; Stiff, Mark A; Fakhouri, Tarek M

    2014-08-01

    Cosmetic, functional, and structural sequelae of scarring are innumerable, and measures exist to optimize and ultimately minimize these sequelae. To evaluate the innumerable methods available to decrease the cosmetic, functional, and structural repercussions of scarring, pubMed search of the English literature with key words scar, scar revision, scar prevention, scar treatment, scar remodeling, cicatrix, cicatrix treatment, and cicatrix remodeling was done. Original articles and reviews were examined and included. Seventy-nine manuscripts were reviewed. Techniques, comparisons, and results were reviewed and tabulated. Overall, though topical modalities are easier to use and are usually more attractive to the patient, the surgical approaches still prove to be superior and more reliable. However, advances in topical medications for scar modification are on the rise and a change towards medical treatment of scars may emerge as the next best approach. Comparison studies of the innumerable specific modalities for scar revision and prevention are impossible. Standardization of techniques is lacking. Scarring, the body's natural response to a wound, can create many adverse effects. At this point, the practice of sound, surgical fundamentals still trump the most advanced preventative methods and revision techniques. Advances in medical approaches are available, however, to assist the scarring process, which even the most advanced surgical fundamentals will ultimately lead to. Whether through newer topical therapies, light treatment, or classical surgical intervention, our treatment armamentarium of scars has expanded and will allow us to maximize scar prevention and to minimize scar morbidity.

  12. Arabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling

    Science.gov (United States)

    Brzezinka, Krzysztof; Altmann, Simone; Czesnick, Hjördis; Nicolas, Philippe; Gorka, Michal; Benke, Eileen; Kabelitz, Tina; Jähne, Felix; Graf, Alexander; Kappel, Christian; Bäurle, Isabel

    2016-01-01

    Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the FORGETTER1 (FGT1) locus, with fgt1 mutants displaying reduced maintenance of heat-induced gene expression. FGT1 encodes the Arabidopsis thaliana orthologue of Strawberry notch (Sno), and the protein globally associates with the promoter regions of actively expressed genes in a heat-dependent fashion. FGT1 interacts with chromatin remodelers of the SWI/SNF and ISWI families, which also display reduced heat stress memory. Genomic targets of the BRM remodeler overlap significantly with FGT1 targets. Accordingly, nucleosome dynamics at loci with altered maintenance of heat-induced expression are affected in fgt1. Together, our results suggest that by modulating nucleosome occupancy, FGT1 mediates stress-induced chromatin memory. DOI: http://dx.doi.org/10.7554/eLife.17061.001 PMID:27680998

  13. [Psychopharmacotherapy in patients with cardiovascular diseases].

    Science.gov (United States)

    Cordes, J; Lange-Asschenfeldt, C; Hiemke, C; Kahl, K G

    2012-11-01

    Increased cardiometabolic morbidity and increased overall mortality has been observed in patients with severe mental disorders. Therefore, cardiometabolic safety is an important issue in the treatment of patients with psychiatric disorders, in particular in patients with comorbid cardiometabolic diseases. Frequent adverse side effects include disturbances of lipid and glucose metabolism, body weight changes and alterations of the QTc interval. Dependent on the particular substance used and on factors concerning individual vulnerability, these side effects vary in relative frequency. Therefore, regular monitoring is recommended including ECG. Furthermore, interactions between different medicaments may occur, either leading to enhanced or decreased drug concentrations. Prior to psychopharmacological treatment, proper cardiological treatment is recommended. The management of cardiovascular risks under psychopharmacology requires interdisciplinary cooperation between the cardiologist, general practitioner and psychiatrist.

  14. A clinical approach to obstructive sleep apnea as a risk factor for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Maeder MT

    2016-03-01

    Full Text Available Micha T Maeder,1 Otto D Schoch,2 Hans Rickli1 1Department of Cardiology, 2Department of Respiratory Medicine, Kantonsspital St Gallen, St Gallen, Switzerland Abstract: Obstructive sleep apnea (OSA is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA. Keywords: obstructive sleep apnea, cardiovascular, risk, heart failure, atrial fibrillation, hypertension

  15. Cardiovascular physiology and sleep.

    Science.gov (United States)

    Murali, Narayana S; Svatikova, Anna; Somers, Virend K

    2003-05-01

    Sleep is a natural periodic suspension of consciousness during which processes of rest and restoration occur. The cognitive, reparative and regenerative accompaniments of sleep appear to be essential for maintenance of health and homeostasis. This brief overview will examine the cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications. In the past, sleep was believed to be a passive state. The tableau of sleep as it unfolds is anything but a passive process. The brain's activity is as complex as wakefulness, never "resting" during sleep. Following the demise of the 'passive theory of sleep' (the reticular activating system is fatigued during the waking day and hence becomes inactive), there arose the 'active theory of sleep' (sleep is due to an active general inhibition of the brain) (1). Hess demonstrated the active nature of sleep in cats, inducing "physiological sleep" with electrical stimulation of the diencephalon (2). Classical experiments of transection of the cat brainstem (3) at midpontine level inhibited sleep completely, implying that centers below this level were involved in the induction of sleep (1, 4). For the first time, measurement of sleep depth without awakening the sleeper using the electroencephalogram (EEG) was demonstrated in animals by Caton and in humans, by Berger (1). This was soon followed by discovery of the rapid eye movement sleep periods (REM) by Aserinski and Kleitman (5), demonstration of periodical sleep cycles and their association with REM sleep (6, 7). Multiple studies and steady discoveries (4) made polysomnography, with its ability to perform simultaneous whole night recordings of EEG, electromyogram (EMG), and electrooculogram (EOC), a major diagnostic tool in study of sleep disorders. This facility has been of further critical importance in allowing evaluation of the interaction between sleep and changes in hemodynamics and autonomic cardiovascular control. Consequently the

  16. [Cutaneous adverse effects of TNFalpha antagonists].

    Science.gov (United States)

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  17. Early adversity, neural development, and inflammation.

    Science.gov (United States)

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E

    2015-12-01

    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  18. Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

    Science.gov (United States)

    2010-01-01

    Background Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9). Results Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis. Conclusions As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. PMID:20735854

  19. Osteoporosis y enfermedad cardiovascular

    OpenAIRE

    Sarahí Mendoza; Miriam Noa; Rosa Más

    2007-01-01

    Las enfermedades cardiovasculares (ECV) y la osteoporosis son causas frecuentes de morbilidad en la población adulta, cuya frecuencia aumenta con la edad, por lo que al aumentar la expectativa de vida, constituyen importantes problemas de salud. El riesgo a padecer ambas patologías depende de factores de riesgo, y la prevención consiste en controlar los modificables. Las ECV y la osteoporosis presentan factores etiológicos comunes que involucran la biosíntesis del colesterol y la oxidación li...

  20. Postnatal Cardiovascular Adaptation

    Directory of Open Access Journals (Sweden)

    Ferda Ozlu

    2016-06-01

    Full Text Available Fetus depends on placental circulation in utero. A successful transition from intrauterin to extrauterine life depends on succesful physiological changes during labor. During delivery, fetus transfers from a liquid environment where oxygen comes via umbilical vein to air environement where oxygenation is supported via air breathing. Endocrinological changes are important for fetus to adapt to extrauterine life. In addition to these, cord clemping plays a crucial role in postnatal adaptation. Establishment of neonatal postnatal life and succesful overcome, the fetal cardiovascular transition period are important to stay on. [Archives Medical Review Journal 2016; 25(2.000: 181-190

  1. Cardiovascular hypertensive emergencies.

    Science.gov (United States)

    Papadopoulos, D P; Sanidas, E A; Viniou, N A; Gennimata, V; Chantziara, V; Barbetseas, I; Makris, T K

    2015-02-01

    Inevitably, a small proportion of patients with systematic hypertension will develop hypertensive crisis at some point. Hypertensive crises can be divided into hypertensive emergency or hypertensive urgency according to the presence or lack of acute target organ damage. In this review, we discuss cardiovascular hypertensive emergencies, including acute coronary syndrome, aortic dissection, congestive heart failure, and sympathomimetic hypertensive crises, including those caused by cocaine use. Each presents in a unique fashion, although some hypertensive emergency patients report nonspecific symptoms. Treatment includes several effective and rapid-acting medications to safely reduce the blood pressure, protect remaining end-organ function, relieve symptoms, minimize the risk of complications, and thereby improve patient outcomes.

  2. Fetal cardiovascular physiology.

    Science.gov (United States)

    Rychik, J

    2004-01-01

    The cardiovascular system of the fetus is physiologically different than the adult, mature system. Unique characteristics of the myocardium and specific channels of blood flow differentitate the physiology of the fetus from the newborn. Conditions of increased preload and afterload in the fetus, such as sacrococcygeal teratoma and twin-twin transfusion syndrome, result in unique and complex pathophysiological states. Echocardiography has improved our understanding of human fetal cadiovasvular physiology in the normal and diseased states, and has expanded our capability to more effectively treat these disease processes.

  3. Antioxidantes y enfermedad cardiovascular

    OpenAIRE

    Vázquez, Clotilde

    2004-01-01

    La enfermedad cardiovascular se mantiene como la más importante causa de morbi y mortalidad en la mayoría de los países desarrollados, siendo cada vez más frecuente en los países en vías de desarrollo. La orteroesclerosis es un enfermedad crónica de las arterias de mediano y gran calibre, caracterizadas por el endurecimiento y pérdida de elasticidad de su pared, que se acompaña de estrechamiento de su luz. En general, la lesión arteriosclerótica se desarrolla en tres fases: a) inici...

  4. Pharmacogenetics of cardiovascular drug therapy

    OpenAIRE

    Peters, Bas J.M.; Olaf H Klungel; de Boer, Anthonius; Ch Stricker, Bruno H; Maitland-van der Zee, Anke-Hilse

    2009-01-01

    In developed countries cardiovascular disease is one of the leading causes of death. Cardiovascular drugs such as platelet aggregation inhibitors, oral anticoagulants, antihypertensives and cholesterol lowering drugs are abundantly prescribed to reduce risk of cardiovascular disease. Notable interindividual variation exists in the response to these pharmacotherapeutic interventions, which can be partially explained by factors such as gender, age, diet, concomitant drug use and environmental f...

  5. Hospital deaths and adverse events in Brazil

    Directory of Open Access Journals (Sweden)

    Pavão Ana Luiza B

    2011-09-01

    Full Text Available Abstract Background Adverse events are considered a major international problem related to the performance of health systems. Evaluating the occurrence of adverse events involves, as any other outcome measure, determining the extent to which the observed differences can be attributed to the patient's risk factors or to variations in the treatment process, and this in turn highlights the importance of measuring differences in the severity of the cases. The current study aims to evaluate the association between deaths and adverse events, adjusted according to patient risk factors. Methods The study is based on a random sample of 1103 patient charts from hospitalizations in the year 2003 in 3 teaching hospitals in the state of Rio de Janeiro, Brazil. The methodology involved a retrospective review of patient charts in two stages - screening phase and evaluation phase. Logistic regression was used to evaluate the relationship between hospital deaths and adverse events. Results The overall mortality rate was 8.5%, while the rate related to the occurrence of an adverse event was 2.9% (32/1103 and that related to preventable adverse events was 2.3% (25/1103. Among the 94 deaths analyzed, 34% were related to cases involving adverse events, and 26.6% of deaths occurred in cases whose adverse events were considered preventable. The models tested showed good discriminatory capacity. The unadjusted odds ratio (OR 11.43 and the odds ratio adjusted for patient risk factors (OR 8.23 between death and preventable adverse event were high. Conclusions Despite discussions in the literature regarding the limitations of evaluating preventable adverse events based on peer review, the results presented here emphasize that adverse events are not only prevalent, but are associated with serious harm and even death. These results also highlight the importance of risk adjustment and multivariate models in the study of adverse events.

  6. Asymmetric Information – Adverse Selection Problem

    Directory of Open Access Journals (Sweden)

    Dumitru MARIN

    2007-01-01

    Full Text Available The present paper makes an introduction in the contract theory starting with the definitions of asymmetric information and some of the problems that generate: moral hazard and adverse selection. We provide an insight of the latest empirical studies in adverse selection in different markets. An adverse selection model, based on Rothchild and Stiglitz is also present to give a perspective of the theoretical framework.

  7. Oxidative Stress in Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Gábor Csányi

    2014-04-01

    Full Text Available In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine.

  8. MACD: an imaging marker for cardiovascular disease

    Science.gov (United States)

    Ganz, Melanie; de Bruijne, Marleen; Nielsen, Mads

    2010-03-01

    Despite general acceptance that a healthy lifestyle and the treatment of risk factors can prevent the development of cardiovascular diseases (CVD), CVD are the most common cause of death in Europe and the United States. It has been shown that abdominal aortic calcifications (AAC) correlate strongly with coronary artery calcifications. Hence an early detection of aortic calcified plaques helps to predict the risk of related coronary diseases. Also since two thirds of the adverse events have no prior symptoms, possibilities to screen for risk in low cost imaging are important. To this end the Morphological Atherosclerotic Calcification Distribution (MACD) index was developed. In the following several potential severity scores relating to the geometrical outline of the calcified deposits in the lumbar aortic region are introduced. Their individual as well as their combined predictive power is examined and a combined marker, MACD, is constructed. This is done using a Cox regression analysis, also known as survival analysis. Furthermore we show how a Cox regression yields MACD to be the most efficient marker. We also demonstrate that MACD has a larger individual predictive power than any of the other individual imaging markers described. Finally we present that the MACD index predicts cardiovascular death with a hazard ratio of approximately four.

  9. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1

    DEFF Research Database (Denmark)

    Bai, Bo; Man, Andy W C; Yang, Kangmin;

    2016-01-01

    for the prevention of vascular ageing. Methods and Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear compartment of endothelial cells. Site...

  10. Cutaneous remodeling and photorejuvenation using radiofrequency devices

    Directory of Open Access Journals (Sweden)

    Elsaie Mohamed

    2009-01-01

    Full Text Available Radio frequency (RF is electromagnetic radiation in the frequency range of 3-300GHz. The primary effects of RF energy on living tissue are considered to be thermal. The goal of the new devices based on these frequency ranges is to heat specific layers of the skin. The directed use of RF can induce dermal heating and cause collagen degeneration. Wound healing mechanisms promote the remodeling of collagen and wound contraction, which ultimately clinically enhances the appearance of mild to moderate skin laxity. Preliminary studies have reported efficacy in the treatment of laxity that involves the periorbital area and jowls. Because RF energy is not dependent on specific chromophore interaction, epidermal melanin is not at risk of destruction and treatment of all skin types is possible. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision and treatment of unwanted hair, vascular lesions and inflammatory acne. The use of RF is becoming more popular, although a misunderstanding exists regarding the mechanisms and limitations of its actions. This concise review serves as an introduction and guide to many aspects of RF in the non ablative rejuvenation of skin.

  11. Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

    OpenAIRE

    Cowling, Belinda S; Anne Toussaint; Jean Muller; Jocelyn Laporte

    2012-01-01

    Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Too...

  12. Cardiovascular benefits of exercise

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    Agarwal SK

    2012-06-01

    Full Text Available Shashi K AgarwalMedical Director, Agarwal Health Center, NJ, USAAbstract: Regular physical activity during leisure time has been shown to be associated with better health outcomes. The American Heart Association, the Centers for Disease Control and Prevention and the American College of Sports Medicine all recommend regular physical activity of moderate intensity for the prevention and complementary treatment of several diseases. The therapeutic role of exercise in maintaining good health and treating diseases is not new. The benefits of physical activity date back to Susruta, a 600 BC physician in India, who prescribed exercise to patients. Hippocrates (460–377 BC wrote “in order to remain healthy, the entire day should be devoted exclusively to ways and means of increasing one's strength and staying healthy, and the best way to do so is through physical exercise.” Plato (427–347 BC referred to medicine as a sister art to physical exercise while the noted ancient Greek physician Galen (129–217 AD penned several essays on aerobic fitness and strengthening muscles. This article briefly reviews the beneficial effects of physical activity on cardiovascular diseases.Keywords: exercise, cardiovascular disease, lifestyle changes, physical activity, good health

  13. Resveratrol and Cardiovascular Diseases

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    Dominique Bonnefont-Rousselot

    2016-05-01

    Full Text Available The increased incidence of cardiovascular diseases (CVDs has stimulated research for substances that could improve cardiovascular health. Among them, resveratrol (RES, a polyphenolic compound notably present in grapes and red wine, has been involved in the “French paradox”. RES is known for its antioxidant and anti-inflammatory properties and for its ability to upregulate endothelial NO synthase (eNOS. RES was able to scavenge •OH/O2•− and peroxyl radicals, which can limit the lipid peroxidation processes. Moreover, in bovine aortic endothelial cells (BAEC under glucose-induced oxidative stress, RES restored the activity of dimethylargininedimethylaminohydrolase (DDAH, an enzyme that degrades an endogenous inhibitor of eNOS named asymmetric dimethylarginine (ADMA. Thus, RES could improve •NO availability and decrease the endothelial dysfunction observed in diabetes. Preclinical studies have made it possible to identify molecular targets (SIRT-1, AMPK, Nrf2, NFκB…; however, there are limited human clinical trials, and difficulties in the interpretation of results arise from the use of high-dose RES supplements in research studies, whereas low RES concentrations are present in red wine. The discussions on potential beneficial effects of RES in CVDs (atherosclerosis, hypertension, stroke, myocardial infarction, heart failure should compare the results of preclinical studies with those of clinical trials.

  14. Cardiovascular Complications of Pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Carolina Gongora

    2015-10-01

    Full Text Available Pregnancy causes significant metabolic and hemodynamic changes in a woman’s physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia, gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.

  15. Cardiovascular Complications of Pregnancy.

    Science.gov (United States)

    Gongora, Maria Carolina; Wenger, Nanette K

    2015-10-09

    Pregnancy causes significant metabolic and hemodynamic changes in a woman's physiology to allow for fetal growth. The inability to adapt to these changes might result in the development of hypertensive disorders of pregnancy (hypertension, preeclampsia or eclampsia), gestational diabetes and preterm birth. Contrary to previous beliefs these complications are not limited to the pregnancy period and may leave permanent vascular and metabolic damage. There is in addition, a direct association between these disorders and increased risk of future cardiovascular disease (CVD, including hypertension, ischemic heart disease, heart failure and stroke) and diabetes mellitus. Despite abundant evidence of this association, women who present with these complications of pregnancy do not receive adequate postpartum follow up and counseling regarding their increased risk of future CVD. The postpartum period in these women represents a unique opportunity to intervene with lifestyle modifications designed to reduce the development of premature cardiovascular complications. In some cases it allows early diagnosis and treatment of chronic hypertension or diabetes mellitus. The awareness of this relationship is growing in the medical community, especially among obstetricians and primary care physicians, who play a pivotal role in detecting these complications and assuring appropriate follow up.

  16. [Methodology for Estimating the Risk of Adverse Drug Reactions in Pregnant Women: Analysis of the Japanese Adverse Drug Event Report Database].

    Science.gov (United States)

    Sakai, Takamasa; Ohtsu, Fumiko; Sekiya, Yasuaki; Mori, Chiyo; Sakata, Hiroshi; Goto, Nobuyuki

    2016-01-01

    Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.

  17. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Zhang X

    2016-12-01

    Full Text Available Xinlu Zhang,1,* Xu Wang,2,* Feng Hu,1 Boda Zhou,3 Hai-Bin Chen,1 Daogang Zha,1 Yili Liu,1 Yansong Guo,4 Lemin Zheng,2 Jiancheng Xiu1 1Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, 2The Institute of Cardiovascular Sciences and Institute of Systems Biomedicine, School of Basic Medical Sciences, and Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, Peking University Health Science Center, 3Department of Cardiology, Key Laboratory of Molecular Cardiovascular Sciences of Ministry of Education, and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Ministry of Health, Peking University Third Hospital, Beijing, 4Department of Cardiovascular Medicine, Fujian Provincial Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Drag-reducing polymers (DRPs, when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR. Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS or DRPs. Body weight (BW, heart rate (HR and systolic blood pressure (SBP were measured. Echocardiography was used to evaluate the changes in left ventricle (LV function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1 of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end

  18. KyoT2 downregulates airway remodeling in asthma.

    Science.gov (United States)

    Hu, Mei; Ou-Yang, Hai-Feng; Han, Xing-Peng; Ti, Xin-Yu; Wu, Chang-Gui

    2015-01-01

    The typical pathological features of asthma are airway remodeling and airway hyperresponsiveness (AHR). KyoT2, a negative modulator of Notch signaling, has been linked to asthma in several previous studies. However, whether KyoT2 is involved in the regulation of airway remodeling or the modulation of airway resistance in asthma is unclear. In this study, we aimed to evaluate the therapeutic potential of KyoT2 in preventing asthma-associated airway remodeling and AHR. BALB/c mice were used to generate a mouse model of asthma. Additionally, the expression of Hes1 and Notch1 in airway was analyzed using Immunofluorescence examination. The asthmatic mice were intranasally administered adenovirus expressing KyoT2 and were compared to control groups. Furthermore, subepithelial fibrosis and other airway remodeling features were analyzed using hematoxylin and eosin staining, Van Gieson's staining and Masson's trichrome staining. AHR was also evaluated. This study revealed that KyoT2 downregulated the expression of Hes1, repressed airway remodeling, and alleviated AHR in asthmatic mice. It is reasonable to assume that KyoT2 downregulates airway remodeling and resistance in asthmatic mice through a Hes1-dependent mechanism. Therefore, KyoT2 is a potential clinical treatment strategy for asthma.

  19. Optimal management of acute nonrenal adverse reactions to iodine-based contrast media

    Directory of Open Access Journals (Sweden)

    Nielsen YW

    2013-06-01

    Full Text Available Yousef W Nielsen, Henrik S Thomsen Department of Radiology, Copenhagen University Hospital Herlev, Copenhagen, Denmark Abstract: Acute adverse reactions to iodine-based contrast media occur within 60 minutes of administration. The reactions range from mild (flushing, arm pain, nausea/vomiting, headache to moderate (bronchospasm, hypotension, and severe (cardiovascular collapse, laryngeal edema, convulsions, arrhythmias. Most acute adverse reactions occur in an unpredictable manner. Use of the older group of ionic iodine-based contrast agents increases the risk of acute adverse reactions. Other risk factors include previous reactions to contrast media, asthma, and allergic conditions. The exact pathophysiology of the acute adverse reactions is unknown, but some of the reactions are pseudoallergic mimicking type 1 allergic reactions. As antibodies against contrast media have not been consistently demonstrated, the reactions are, in most cases, not truly allergic in nature. Most of the severe and fatal adverse reactions occur within the first 20 minutes after injection. Thus, it is important that patients are observed in the radiology department during this period. The radiologist should be near the room where contrast media is administered, and be ready to treat any acute nonrenal adverse reaction. Appropriate drugs and resuscitation equipment should be in/near the room where the contrast media is administered. The important first-line management of acute adverse reactions includes the establishment of an adequate airway, oxygen supplementation by mask, intravenous fluid administration, and measurement of blood pressure and heart rate. When severe anaphylactoid reactions occur, adrenaline should be given intramuscularly. Only one concentration of adrenaline (1:1000–1 mg/mL should be available in the radiology department to avoid dosing errors in stressful acute settings. Resuscitation team specialists should be the only ones giving intravenous

  20. Streptokinase Adverse Reactions: A Review of Iranian Literature

    Directory of Open Access Journals (Sweden)

    Ava Mansouri

    2015-10-01

    Full Text Available Thrombolytic agents are among the medications that are used widely for the treatment of thromboembolic disorders and myocardial infarction (MI. Despite the world-wide availability of newer specific agents, streptokinase (SK is still the most frequently used medication from this class in Iran. Hence we conducted this study to review the adverse reactions to this medication which were reported in the Iranian studies. We preformed this study by searching the English resources such as Pubmed, Google scholar and Scopus. Additionally, we searched Google scholar, Scientific Information Database, Magiran and IranMedex to cover Persian articles.We found 50 articles from the mentioned resources after deleting the duplicated records. Nineteen articles remained after implementing the inclusion and exclusion criteria. In most of the studies the indication for SK treatment was MI. Assessment of streptokinase ADRs was the main focus of 7 studies. The most frequent adverse drug reaction (ADR was related to the cardiovascular system. Among them arrhythmia and hypotension were the most frequent ones. The second most prevalent ADR was bleeding followed by allergic reactions. In two studies only a single system ADR was studied: neurologic adverse effects and elevation in liver enzymes. Only very limited number of studies assessed the causality of the ADRs which made the interpretation of the results difficult. Among the associated factors that were assessed as risk factors of ADRs, age was the focus of 2 studies. The Iranian studies reported frequent ADRs similar to previous reports. However, due to the heterogeneity of the studies we could not describe the frequency and severity of reported ADRs in a more clear and precise conclusion.

  1. Pharmacogenomics of statins: understanding susceptibility to adverse effects

    Directory of Open Access Journals (Sweden)

    Kitzmiller JP

    2016-10-01

    Full Text Available Joseph P Kitzmiller,1 Eduard B Mikulik,1 Anees M Dauki,2 Chandrama Murkherjee,1 Jasmine A Luzum3 1Department of Biological Chemistry and Pharmacology, College of Medicine, 2College of Pharmacy, The Ohio State University, Columbus, OH, 3Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA Abstract: Statins are a cornerstone of the pharmacologic treatment and prevention of atherosclerotic cardiovascular disease. Atherosclerotic disease is a predominant cause of mortality and morbidity worldwide. Statins are among the most commonly prescribed classes of medications, and their prescribing indications and target patient populations have been significantly expanded in the official guidelines recently published by the American and European expert panels. Adverse effects of statin pharmacotherapy, however, result in significant cost and morbidity and can lead to nonadherence and discontinuation of therapy. Statin-associated muscle symptoms occur in ~10% of patients on statins and constitute the most commonly reported adverse effect associated with statin pharmacotherapy. Substantial clinical and nonclinical research effort has been dedicated to determining whether genetics can provide meaningful insight regarding an individual patient’s risk of statin adverse effects. This contemporary review of the relevant clinical research on polymorphisms in several key genes that affect statin pharmacokinetics (eg, transporters and metabolizing enzymes, statin efficacy (eg, drug targets and pathways, and end-organ toxicity (eg, myopathy pathways highlights several promising pharmacogenomic candidates. However, SLCO1B1 521C is currently the only clinically relevant pharmacogenetic test regarding statin toxicity, and its relevance is limited to simvastatin myopathy. Keywords: cholesterol, myopathy, lipids, muscle toxicity, pharmacokinetics, pharmacogenetics

  2. Biofeedback therapy in cardiovascular disease: rationale and research overview.

    Science.gov (United States)

    Moravec, Christine S

    2008-03-01

    Biofeedback has much therapeutic potential in cardiovascular diseases, since many of these diseases involve dysregulation of the autonomic nervous system. Studies have clearly demonstrated that patients can use biofeedback techniques to regulate the input of the autonomic nervous system to the heart, but the clinical utility of these techniques has not been well explored in systematic trials. Much biofeedback research to date has focused on patients with hypertension, but outcomes have been inconclusive. Preliminary studies suggest that heart rate variability biofeedback may be useful in improving symptoms and quality of life in patients with cardiac disease, and early studies suggest a possible effect of biofeedback on remodeling of the failing heart. Both of these areas require further research, however. Biofeedback is increasingly used as an adjunct to stress management in cardiac rehabilitation programs, providing the impetus for a large-scale, systematic study of self-regulation in cardiac disease.

  3. YKL-40--an emerging biomarker in cardiovascular disease and diabetes

    DEFF Research Database (Denmark)

    Rathcke, Camilla N; Vestergaard, Henrik

    2009-01-01

    Several inflammatory cytokines are involved in vascular inflammation resulting in endothelial dysfunction which is the earliest event in the atherosclerotic process leading to manifest cardiovascular disease. YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction by promoting...... chemotaxis, cell attachment and migration, reorganization and tissue remodelling as a response to endothelial damage. YKL-40 protein expression is seen in macrophages and smooth muscle cells in atherosclerotic plaques with the highest expression seen in macrophages in the early lesion of atherosclerosis....... Several studies demonstrate, that elevated serum YKL-levels are independently associated with the presence and extent of coronary artery disease and even higher YKL-40 levels are documented in patients with myocardial infarction. Moreover, elevated serum YKL-40 levels have also been found to be associated...

  4. Global Longitudinal Strain by Echocardiography Predicts Long-Term Risk of Cardiovascular Morbidity and Mortality in a Low-Risk General Population

    DEFF Research Database (Denmark)

    Biering-Sørensen, Tor; Biering-Sørensen, Sofie Reumert; Olsen, Flemming Javier

    2017-01-01

    BACKGROUND: Global longitudinal strain (GLS) is prognostic of adverse cardiovascular outcomes in various patient populations, but the prognostic utility of GLS for long-term cardiovascular morbidity and mortality in the general population is unknown. METHODS AND RESULTS: A total of 1296 participa...

  5. ESC study group of sports cardiology position paper on adverse cardiovascular effects of doping in athletes.

    NARCIS (Netherlands)

    Deligiannis, A.; Bjornstad, H.; Carre, F.; Heidbuchel, H.; Kouidi, E.; Panhuyzen-Goedkoop, N.M.; Pigozzi, F.; Schanzer, W.; Hees, L. van

    2006-01-01

    The use of doping substances and methods is extensive not only among elite athletes, but also among amateur and recreational athletes. Many types of drugs are used by athletes to enhance performance, to reduce anxiety, to increase muscle mass, to reduce weight or to mask the use of other drugs durin

  6. Reporting of Cardiovascular Medical Device Adverse Events to Pharmaceuticals and Medical Devices Agency, Japan

    Directory of Open Access Journals (Sweden)

    Nobuhiro Handa

    2015-09-01

    Comments: Although Japanese MAHs complied with the obligation to report AEs, they often failed to share AEs with healthcare providers. Registry may be a potential solution, although the cooperation of healthcare providers to input data is essential.

  7. Family history predicts major adverse cardiovascular events (MACE) in young adults with psoriasis

    DEFF Research Database (Denmark)

    Egeberg, Alexander; Bruun, Louise E; Mallbris, Lotus;

    2016-01-01

    and severe disease, respectively. In patients with psoriasis but without a family history of CVD, there was no increased risk of MACE. LIMITATIONS: Results may not apply to late-onset psoriasis. CONCLUSIONS: A family history of CVD predicted the risk of first-time MACE in young adults with psoriasis...

  8. Population-based investigations to study the association of cardiovascular polymorphisms and adverse pregnancy outcome

    DEFF Research Database (Denmark)

    Lykke, Jacob Alexander; Langhoff-Roos, Jens; Young, Bradford

    2007-01-01

    women giving birth from the years 1996 to 2002. In addition, national registers exist which can be linked together. Two studies have been initiated. One is a retrospective cohort study concerning primiparous women, with singleton pregnancy and with no identifiable congenital malformation. The purpose...

  9. Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis

    DEFF Research Database (Denmark)

    Greve, Anders M; Bang, Casper N; Berg, Ronan M G

    2015-01-01

    BACKGROUND: An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown. METHODS: RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS...

  10. Monitoring of incidence, severity, and causality of adverse drug reactions in hospitalized patients with cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Sharminder Kaur

    2011-01-01

    Conclusion : Development of ADR in one of every five cardiac patient points toward a grave situation, but a higher incidence of Type A reactions in cardiology department means that these can be avoided.

  11. Basic science behind the cardiovascular benefits of exercise.

    Science.gov (United States)

    Wilson, Mathew G; Ellison, Georgina M; Cable, N Tim

    2016-01-01

    Cardiorespiratory fitness is a strong predictor of cardiovascular (CV) disease and all-cause mortality, with increases in cardiorespiratory fitness associated with corresponding decreases in CV disease risk. The effects of exercise upon the myocardium and vascular system are dependent upon the frequency, intensity and duration of the exercise itself. Following a prolonged period (≥6 months) of regular intensive exercise in previously untrained individuals, resting and submaximal exercising heart rates are typically 5-20 beats lower, with an increase in stroke volume of ∼20% and enhanced myocardial contractility. Structurally, all four heart chambers increase in volume with mild increases in wall thickness, resulting in greater cardiac mass due to increased myocardial cell size. With this in mind, the present paper aims to review the basic science behind the CV benefits of exercise. Attention will be paid to understanding (1) the relationship between exercise and cardiac remodelling; (2) the cardiac cellular and molecular adaptations in response to exercise, including the examination of molecular mechanisms of physiological cardiac growth and applying these mechanisms to identify new therapeutic targets to prevent or reverse pathological remodelling and heart failure; and (3) vascular adaptations in response to exercise. Finally, this review will briefly examine how to optimise the CV benefits of exercise by considering how much and how intense exercise should be.

  12. Cheese and cardiovascular disease risk

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Tholstrup, Tine

    2016-01-01

    Abstract Currently, the effect of dairy products on cardiovascular risk is a topic with much debate and conflicting results. The purpose of this review is to give an overview of the existing literature regarding the effect of cheese intake and risk of cardiovascular disease (CVD). Studies included...

  13. Multiple adverse experiences and child cognitive development.

    Science.gov (United States)

    Guinosso, Stephanie A; Johnson, Sara B; Riley, Anne W

    2016-01-01

    During childhood and adolescence, children's social environments shape their cognitive development. Children exposed to multiple adversities in their social environment are more likely to have poorer cognitive outcomes. These findings have prompted interest among pediatric and public health communities to screen and connect youth to appropriate interventions that ameliorate the detrimental effects of adverse exposures. Such intervention efforts can be improved with a stronger conceptual understanding of the relationship between multiple adverse exposures and child cognitive development. This includes disentangling adverse exposures from other risk factors or underlying mechanisms, specifying mechanisms of action, and determining when adverse exposures are most detrimental. This review summarizes findings from the literature on each of these areas and proposes a conceptual model to guide further research and intervention.

  14. Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice

    Directory of Open Access Journals (Sweden)

    Wang Hui-Ting

    2012-07-01

    Full Text Available Abstract Background Obesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF and attenuating inflammation, oxidative stress and LV remodeling in obese mice. Methods and results Eight-week-old C57BL/6 J mice (n=24 were equally divided into control (fed a control diet for 22 weeks, obesity (high-fat diet, 22 weeks, and obese reduction (OR (high-fat diet, 14 weeks; then control diet, 8 weeks. Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p Conclusion Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.

  15. Adaptive scapula bone remodeling computational simulation: Relevance to regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Gulshan B., E-mail: gbsharma@ucalgary.ca [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States); University of Calgary, Schulich School of Engineering, Department of Mechanical and Manufacturing Engineering, Calgary, Alberta T2N 1N4 (Canada); Robertson, Douglas D., E-mail: douglas.d.robertson@emory.edu [Emory University, Department of Radiology and Imaging Sciences, Spine and Orthopaedic Center, Atlanta, Georgia 30329 (United States); University of Pittsburgh, Swanson School of Engineering, Department of Bioengineering, Pittsburgh, Pennsylvania 15213 (United States)

    2013-07-01

    Shoulder arthroplasty success has been attributed to many factors including, bone quality, soft tissue balancing, surgeon experience, and implant design. Improved long-term success is primarily limited by glenoid implant loosening. Prosthesis design examines materials and shape and determines whether the design should withstand a lifetime of use. Finite element (FE) analyses have been extensively used to study stresses and strains produced in implants and bone. However, these static analyses only measure a moment in time and not the adaptive response to the altered environment produced by the therapeutic intervention. Computational analyses that integrate remodeling rules predict how bone will respond over time. Recent work has shown that subject-specific two- and three dimensional adaptive bone remodeling models are feasible and valid. Feasibility and validation were achieved computationally, simulating bone remodeling using an intact human scapula, initially resetting the scapular bone material properties to be uniform, numerically simulating sequential loading, and comparing the bone remodeling simulation results to the actual scapula’s material properties. Three-dimensional scapula FE bone model was created using volumetric computed tomography images. Muscle and joint load and boundary conditions were applied based on values reported in the literature. Internal bone remodeling was based on element strain-energy density. Initially, all bone elements were assigned a homogeneous density. All loads were applied for 10 iterations. After every iteration, each bone element’s remodeling stimulus was compared to its corresponding reference stimulus and its material properties modified. The simulation achieved convergence. At the end of the simulation the predicted and actual specimen bone apparent density were plotted and compared. Location of high and low predicted bone density was comparable to the actual specimen. High predicted bone density was greater than

  16. The different role of sex hormones on female cardiovascular physiology and function: not only oestrogens.

    Science.gov (United States)

    Salerni, Sara; Di Francescomarino, Samanta; Cadeddu, Christian; Acquistapace, Flavio; Maffei, Silvia; Gallina, Sabina

    2015-06-01

    Human response to different physiologic stimuli and cardiovascular (CV) adaptation to various pathologies seem to be gender specific. Sex-steroid hormones have been postulated as the major contributors towards these sex-related differences. This review will discuss current evidence on gender differences in CV function and remodelling, and will present the different role of the principal sex-steroid hormones on female heart. Starting from a review of sex hormones synthesis, receptors and CV signalling, we will summarize the current knowledge concerning the role of sex hormones on the regulation of our daily activities throughout the life, via the modulation of autonomic nervous system, excitation-contraction coupling pathway and ion channels activity. Many unresolved questions remain even if oestrogen effects on myocardial remodelling and function have been extensively studied. So this work will focus attention also on the controversial and complex relationship existing between androgens, progesterone and female heart.

  17. Indian poverty and cardiovascular disease.

    Science.gov (United States)

    Ramaraj, Radhakrishnan; Alpert, Joseph Stephen

    2008-07-01

    Cardiovascular disease is among the world's leading causes of death, and nearly 80% of deaths occur in developing countries. Cardiovascular disease is becoming a major health problem in India, where life expectancy has increased with decreases in infectious disease and childhood mortality. It is well established that this population experiences coronary artery disease at a younger age than other populations. With infectious diseases still endemic, noncommunicable diseases are a lower priority for the governments of developing countries. There is a clear progression to degenerative and lifestyle-related diseases such as cardiovascular disease as a result of current social and economic change. The lack of a public response to the increasing risk for cardiovascular disease thus far is due mostly to a perception among policy makers and the public that cardiovascular disease is largely a problem of the urban rich. In conclusion, this review addresses the imminent threats and ways to tackle the epidemic in India.

  18. Assessment of cardiovascular risk.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2010-10-01

    Atherosclerotic cardiovascular disease (CVD) is the most common cause of death worldwide. Usually atherosclerosis is caused by the combined effects of multiple risk factors. For this reason, most guidelines on the prevention of CVD stress the assessment of total CVD risk. The most intensive risk factor modification can then be directed towards the individuals who will derive the greatest benefit. To assist the clinician in calculating the effects of these multiple interacting risk factors, a number of risk estimation systems have been developed. This review address several issues regarding total CVD risk assessment: Why should total CVD risk be assessed? What risk estimation systems are available? How well do these systems estimate risk? What are the advantages and disadvantages of the current systems? What are the current limitations of risk estimation systems and how can they be resolved? What new developments have occurred in CVD risk estimation?

  19. Cardiovascular complications in acromegaly.

    Science.gov (United States)

    Vitale, G; Pivonello, R; Lombardi, G; Colao, A

    2004-09-01

    Cardiovascular morbidity and mortality are increased in acromegaly. In fact, GH and IGF-I excess induces a specific cardiomyopathy. The early stage of acromegaly is characterized by the hyperkinetic syndrome (high heart rate and increased systolic output). Frequently, concentric biventricular hypertrophy and diastolic dysfunction occur in acromegaly, leading to an impaired systolic function ending in heart failure if the disease is untreated or unsuccessfully untreated. Besides, abnormalities of cardiac rhythm and of valves have been also described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes, aggravates the acromegalic cardiomyopathy. The suppression of GH/IGF-I following an efficacious therapy could decrease left ventricular mass and improve cardiac function. In conclusion, a careful evaluation of cardiac function, morphology and activity seems to be mandatory in acromegaly.

  20. Cardiovascular diseases and diabetes

    DEFF Research Database (Denmark)

    Green, A.; Sortso, C.; Jensen, Peter Bjødstrup

    2016-01-01

    We present an investigation of the occurrence of cardiovascular disease in patients with diabetes in Denmark 2000 through 2011. The Diabetes Impact Study 2013 is based on all registrants in the Danish National Diabetes Register as of July 3rd 2013 (n=497,232). Record linkage with the Danish...... of diabetes has been rather constant at higher level in males (around 16-18%) than in females (around 12-14%) during 2000-2011 (incl.). In contrast, the incidence rate of CVD after having diabetes diagnosis has declined from about 4.5 to less than 3 during the same period, with higher declining level...... for males than for females. Efforts to detect diabetes at an earlier stage have not resulted in a reduced occurrence of CVD at the diagnosis of diabetes in Denmark. However, the risk of developing CVD after the diagnosis of diabetes has been declining, possibly reflecting benefits of intensified treatment...

  1. Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes

    Directory of Open Access Journals (Sweden)

    Kones R

    2013-10-01

    Full Text Available Richard KonesCardiometabolic Research Institute, Houston, TX, USAAbstract: Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL cholesterol

  2. Role Models and the Psychological Characteristics That Buffer Low-Socioeconomic-Status Youth from Cardiovascular Risk

    Science.gov (United States)

    Chen, Edith; Lee, William K.; Cavey, Lisa; Ho, Amanda

    2013-01-01

    Little is understood about why some youth from low-socioeconomic-status (SES) environments exhibit good health despite adversity. This study tested whether role models and "shift-and-persist" approaches (reframing stressors more benignly while persisting with future optimism) protect low-SES youth from cardiovascular risk. A total of 163…

  3. Cardiovascular Magnetic Resonance Imaging

    Science.gov (United States)

    Pelc, Norbert

    2000-03-01

    Cardiovascular diseases are a major source of morbidity and mortality in the United States. Early detection of disease can often be used to improved outcomes, either through direct interventions (e.g. surgical corrections) or by causing the patient to modify his or her behavior (e.g. smoking cessation or dietary changes). Ideally, the detection process should be noninvasive (i.e. it should not be associated with significant risk). Magnetic Resonance Imaging (MRI) refers to the formation of images by localizing NMR signals, typically from protons in the body. As in other applications of NMR, a homogeneous static magnetic field ( ~0.5 to 4 T) is used to create ``longitudinal" magnetization. A magnetic field rotating at the Larmor frequency (proportional to the static field) excites spins, converting longitudinal magnetization to ``transverse" magnetization and generating a signal. Localization is performed using pulsed gradients in the static field. MRI can produce images of 2-D slices, 3-D volumes, time-resolved images of pseudo-periodic phenomena such as heart function, and even real-time imaging. It is also possible to acquire spatially localized NMR spectra. MRI has a number of advantages, but perhaps the most fundamental is the richness of the contrast mechanisms. Tissues can be differentiated by differences in proton density, NMR properties, and even flow or motion. We also have the ability to introduce substances that alter NMR signals. These contrast agents can be used to enhance vascular structures and measure perfusion. Cardiovascular MRI allows the reliable diagnosis of important conditions. It is possible to image the blood vessel tree, quantitate flow and perfusion, and image cardiac contraction. Fundamentally, the power of MRI as a diagnostic tool stems from the richness of the contrast mechanisms and the flexibility in control of imaging parameters.

  4. Perinatal inflammation: a common factor in the early origins of cardiovascular disease?

    Science.gov (United States)

    Nguyen, Maria U; Wallace, Megan J; Pepe, Salvatore; Menheniott, Trevelyan R; Moss, Timothy J; Burgner, David

    2015-10-01

    Cardiovascular disease continues to be the leading cause of global morbidity and mortality. Traditional risk factors account for only part of the attributable risk. The origins of atherosclerosis are in early life, a potential albeit largely unrecognized window of opportunity for early detection and treatment of subclinical cardiovascular disease. There are robust epidemiological data indicating that poor intrauterine growth and/or prematurity, and perinatal factors such as maternal hypercholesterolaemia, smoking, diabetes and obesity, are associated with adverse cardiovascular intermediate phenotypes in childhood and adulthood. Many of these early-life risk factors result in a heightened inflammatory state. Inflammation is a central mechanism in the development of atherosclerosis and cardiovascular disease, but few studies have investigated the role of overt perinatal infection and inflammation (chorioamnionitis) as a potential contributor to cardiovascular risk. Limited evidence from human and experimental models suggests an association between chorioamnionitis and cardiac and vascular dysfunction. Early life inflammatory events may be an important mechanism in the early development of cardiovascular risk and may provide insights into the associations between perinatal factors and adult cardiovascular disease. This review aims to summarise current data on the early life origins of atherosclerosis and cardiovascular disease, with particular focus on perinatal inflammation.

  5. Nitrergic system and plasmatic methylarginines: Evidence of their role in the perinatal programming of cardiovascular diseases.

    Science.gov (United States)

    Bassareo, Pier Paolo; Mussap, Michele; Bassareo, Valentina; Flore, Giovanna; Mercuro, Giuseppe

    2015-12-01

    Atherosclerosis, in turn preceded by endothelial dysfunction, underlies a series of important cardiovascular diseases. Reduced bioavailability of endothelial nitric oxide, by increasing vascular tone and promoting platelet aggregation, leukocyte adhesion, and smooth muscle cell proliferation, plays a key role in the onset of the majority of cardiovascular diseases. In addition, high blood levels of asymmetric dimethylarginine, a potent inhibitor of nitric oxide synthesis, are associated with future development of adverse cardiovascular events and cardiac death. Recent reports have demonstrated that another methylarginine, i.e., symmetric dimethylarginine, is also involved in the onset of endothelial dysfunction and hypertension. Almost a decade ago, prematurity at birth and intrauterine growth retardation were first associated with a potential negative influence on the cardiovascular apparatus, thus constituting risk factors or leading to early onset of cardiovascular diseases. This condition is referred to as cardiovascular perinatal programming. Accordingly, cardiovascular morbidity and mortality are higher among former preterm adults than in those born at term. The aim of this paper was to undertake a comprehensive literature review focusing on cellular and biochemical mechanisms resulting in both reduced nitric oxide bioavailability and increased methylarginine levels in subjects born preterm. Evidence of the involvement of these compounds in the perinatal programming of cardiovascular risk are also discussed.

  6. Plasma asymmetric dimethylarginine and adverse events in patients with atrial fibrillation referred for coronary angiogram.

    Directory of Open Access Journals (Sweden)

    Tze-Fan Chao

    Full Text Available OBJECTIVES: Elevated plasma levels of asymmetric dimethylarginine (ADMA have been reported to be associated with endothelial dysfunction, inflammation, and oxidative stress in multiple cardiovascular diseases. This study aimed to investigate whether ADMA was a predictor of clinical outcomes in atrial fibrillation (AF. METHODS AND RESULTS: From 2006-2009, 990 individuals were referred to our institution for coronary angiography. Among these patients, 141 subjects with a diagnosis of AF, including 52 paroxysmal AF (PAF and 89 non-paroxysmal AF (non-PAF patients, were identified as the study population. Plasma ADMA levels were measured. An adverse event was defined as the occurrence of ischemic stroke or cardiovascular death. The ADMA levels were higher in AF than non-AF patients (0.50 ± 0.13 versus 0.45 ± 0.07 µmol/L; p<0.001. Besides, non-PAF patients had higher ADMA levels than PAF patients (0.52 ± 0.15 versus 0.48 ± 0.08 µmol/L; p<0.001. During the follow-up of 30.7±14.4 months, 21 patients (14.9% experienced adverse events, including cardiovascular death in 7 patients and ischemic stroke in 14. ADMA level, CHA2DS2-VASc score, and left atrial diameter were independent predictors of adverse events in the multivariate analysis. At a cutoff-value of 0.55 µmol/L, the Kaplan-Meier survival analysis showed that patients with a high ADMA level had a higher event rate during the follow-up period. CONCLUSIONS: A higher level of ADMA was a risk factor of adverse events in AF patients, which was independent from the CHA2DS2-VASc score. It deserves to further study whether ADMA could potentially refine the clinical risk stratification in AF.

  7. Synergistic childhood adversities and complex adult psychopathology.

    Science.gov (United States)

    Putnam, Karen T; Harris, William W; Putnam, Frank W

    2013-08-01

    Numerous studies find a cumulative effect of different types of childhood adversities on increasing risk for serious adult mental and medical outcomes. This study uses the National Comorbidity Survey-Replication sample to investigate the cumulative impact of 8 childhood adversities on complex adult psychopathology as indexed by (a) number of lifetime diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994); (b) number of 4 DSM-IV disorder categories (mood, anxiety, impulse control, and substance abuse disorders); and (c) coexistence of internalizing and externalizing disorders. Seven of the 8 childhood adversities were significantly associated with complex adult psychopathology. Individuals with 4 or more childhood adversities had an odds ratio of 7.3, 95% confidence interval [4.7, 11.7] for 4 disorder categories. Additive and multiplicative synergistic effects increasing adult psychopathology were found for specific pairwise combinations of childhood adversities. Synergistic patterns differed by gender suggesting that women are more impacted by sexual abuse and men by economic hardship. The absence of childhood adversities was protective, in that it significantly decreased an individual's risk for subsequent adult mental illness. The results support the clinical impression that increased childhood adversity is associated with more complex adult psychopathology.

  8. [Muscle-related adverse effects of statins].

    Science.gov (United States)

    Pohjola-Sintonen, Sinikka; Julkunen, Heikki

    2014-01-01

    Adverse effects on muscles occur in approximately 5 to 10% of patients taking statins. Drug interactions, associated diseases, agedness, low body weight, high statin dose and hereditary factors increase the risk of adverse effects. In most cases the muscle effects are mild and disappear upon discontinuation of the medication. Rhabdomyolysis is a severe though rare complication that can possibly result in renal damage. A totally different muscle-related adverse effect, necrotizing myopathy, has recently been linked to the use of statins. Its characteristic feature is progression of the symptoms in spite of discontinuation of the statin.

  9. Adverse metabolic response to regular exercise: is it a rare or common occurrence?

    Directory of Open Access Journals (Sweden)

    Claude Bouchard

    Full Text Available BACKGROUND: Individuals differ in the response to regular exercise. Whether there are people who experience adverse changes in cardiovascular and diabetes risk factors has never been addressed. METHODOLOGY/PRINCIPAL FINDINGS: An adverse response is defined as an exercise-induced change that worsens a risk factor beyond measurement error and expected day-to-day variation. Sixty subjects were measured three times over a period of three weeks, and variation in resting systolic blood pressure (SBP and in fasting plasma HDL-cholesterol (HDL-C, triglycerides (TG, and insulin (FI was quantified. The technical error (TE defined as the within-subject standard deviation derived from these measurements was computed. An adverse response for a given risk factor was defined as a change that was at least two TEs away from no change but in an adverse direction. Thus an adverse response was recorded if an increase reached 10 mm Hg or more for SBP, 0.42 mmol/L or more for TG, or 24 pmol/L or more for FI or if a decrease reached 0.12 mmol/L or more for HDL-C. Completers from six exercise studies were used in the present analysis: Whites (N = 473 and Blacks (N = 250 from the HERITAGE Family Study; Whites and Blacks from DREW (N = 326, from INFLAME (N = 70, and from STRRIDE (N = 303; and Whites from a University of Maryland cohort (N = 160 and from a University of Jyvaskyla study (N = 105, for a total of 1,687 men and women. Using the above definitions, 126 subjects (8.4% had an adverse change in FI. Numbers of adverse responders reached 12.2% for SBP, 10.4% for TG, and 13.3% for HDL-C. About 7% of participants experienced adverse responses in two or more risk factors. CONCLUSIONS/SIGNIFICANCE: Adverse responses to regular exercise in cardiovascular and diabetes risk factors occur. Identifying the predictors of such unwarranted responses and how to prevent them will provide the foundation for personalized exercise prescription.

  10. Simvastatin Modulates Remodeling of Kv4.3 Expression in Rat Hypertrophied Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Feifei Su, Miaoqian Shi, Zhiqiang Yan, Dongbo Ou, Juntang Li, Zifan Lu, Qiangsun Zheng

    2012-01-01

    Full Text Available Objectives: Hypertrophy has been shown to be associated with arrhythmias which can be caused by abnormal remodeling of the Kv4-family of transient potassium channels. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins have recently been shown to exert pleiotropic protective effects in cardiovascular diseases, including anti-arrhythmias. It is hypothesized that remodeling of Kv4.3 occurs in rat hypertrophied cardiomyocytes and is regulated by simvastatin.Methods: Male Sprague-Dawley rats and neonatal rat ventricular myocytes (NRVMs underwent abdominal aortic banding (AAB for 7 weeks and angiotensin II (AngII treatment, respectively, to induce cardiac hypertrophy. Kv4.3 expression by NRVMs and myocardium (subepicardial and subendocardial in the left ventricle was measured. The transient outward potassium current (Ito of NRVMs was recorded using a whole-cell patch-clamp method.Results: Expression of the Kv4.3 transcript and protein was significantly reduced in myocardium (subepicardial and subendocardial in the left ventricle and in NRVMs. Simvastatin partially prevented the reduction of Kv4.3 expression in NRVMs and subepicardial myocardium but not in the subendocardial myocardium. Hypertrophied NRVMs exhibited a significant reduction in the Ito current and this effect was partially reversed by simvastatin.Conclusions: Simvastatin alleviated the reduction of Kv4.3 expression, Ito currents in hypertrophied NRVMs and alleviated the reduced Kv4.3 expression in subepicardial myocardium from the hypertrophied left ventricle. It can be speculated that among the pleiotropic effects of simvastatin, the anti-arrhythmia effect is partly mediated by its effect on Kv4.3.

  11. Drinking citrus fruit juice inhibits vascular remodeling in cuff-induced vascular injury mouse model.

    Science.gov (United States)

    Ohnishi, Arika; Asayama, Rie; Mogi, Masaki; Nakaoka, Hirotomo; Kan-No, Harumi; Tsukuda, Kana; Chisaka, Toshiyuki; Wang, Xiao-Li; Bai, Hui-Yu; Shan, Bao-Shuai; Kukida, Masayoshi; Iwanami, Jun; Horiuchi, Masatsugu

    2015-01-01

    Citrus fruits are thought to have inhibitory effects on oxidative stress, thereby attenuating the onset and progression of cancer and cardiovascular disease; however, there are few reports assessing their effect on vascular remodeling. Here, we investigated the effect of drinking the juice of two different citrus fruits on vascular neointima formation using a cuff-induced vascular injury mouse model. Male C57BL6 mice were divided into five groups as follows: 1) Control (water) (C), 2) 10% Citrus unshiu (CU) juice (CU10), 3) 40% CU juice (CU40), 4) 10% Citrus iyo (CI) juice (CI10), and 5) 40% CI juice (CI40). After drinking them for 2 weeks from 8 weeks of age, cuff injury was induced by polyethylene cuff placement around the femoral artery. Neointima formation was significantly attenuated in CU40, CI10 and CI40 compared with C; however, no remarkable preventive effect was observed in CU10. The increases in levels of various inflammatory markers including cytokines such as monocyte chemotactic protein-1, interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α in response to vascular injury did not differ significantly between C, CU10 and CI10. The increases in cell proliferation and superoxide anion production were markedly attenuated in CI10, but not in CU10 compared with C. The increase in phosphorylated ERK expression was markedly attenuated both in CU10 and CI10 without significant difference between CU10 and CI10. Accumulation of immune cells did not differ between CU10 and CI10. These results indicate that drinking citrus fruit juice attenuates vascular remodeling partly via a reduction of oxidative stress. Interestingly, the preventive efficacy on neointima formation was stronger in CI than in CU at least in part due to more prominent inhibitory effects on oxidative stress by CI.

  12. miRNA-132 orchestrates chromatin remodeling and translational control of the circadian clock.

    Science.gov (United States)

    Alvarez-Saavedra, Matías; Antoun, Ghadi; Yanagiya, Akiko; Oliva-Hernandez, Reynaldo; Cornejo-Palma, Daniel; Perez-Iratxeta, Carolina; Sonenberg, Nahum; Cheng, Hai-Ying M

    2011-02-15

    Mammalian circadian rhythms are synchronized to the external time by daily resetting of the suprachiasmatic nucleus (SCN) in response to light. As the master circadian pacemaker, the SCN coordinates the timing of diverse cellular oscillators in multiple tissues. Aberrant regulation of clock timing is linked to numerous human conditions, including cancer, cardiovascular disease, obesity, various neurological disorders and the hereditary disorder familial advanced sleep phase syndrome. Additionally, mechanisms that underlie clock resetting factor into the sleep and physiological disturbances experienced by night-shift workers and travelers with jet lag. The Ca(2+)/cAMP response element-binding protein-regulated microRNA, miR-132, is induced by light within the SCN and attenuates its capacity to reset, or entrain, the clock. However, the specific targets that are regulated by miR-132 and underlie its effects on clock entrainment remained elusive until now. Here, we show that genes involved in chromatin remodeling (Mecp2, Ep300, Jarid1a) and translational control (Btg2, Paip2a) are direct targets of miR-132 in the mouse SCN. Coordinated regulation of these targets underlies miR-132-dependent modulation of Period gene expression and clock entrainment: the mPer1 and mPer2 promoters are bound to and transcriptionally activated by MeCP2, whereas PAIP2A and BTG2 suppress the translation of the PERIOD proteins by enhancing mRNA decay. We propose that miR-132 is selectively enriched for chromatin- and translation-associated target genes and is an orchestrator of chromatin remodeling and protein translation within the SCN clock, thereby fine-tuning clock entrainment. These findings will further our understanding of mechanisms governing clock entrainment and its involvement in human diseases.

  13. Nrf2 and cardiovascular defense.

    Science.gov (United States)

    Howden, Reuben

    2013-01-01

    The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  14. Nrf2 and Cardiovascular Defense

    Directory of Open Access Journals (Sweden)

    Reuben Howden

    2013-01-01

    Full Text Available The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E 2-related factor 2 (Nrf2, regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis. The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

  15. Adverse drug reactions to ibuprofen: a case report

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    Khobragade Yadneshwar

    2016-02-01

    Full Text Available Ibuprofen is a commonly used drug available by prescription and over the counter for treatment of fever, joint pain, headache, migraine, inflammatory states. It is available in combination with paracetamol and various other drugs. Side effects associated with aspirin and non-steroidal anti-inflammatory drugs (NSAIDs are rash, gastrointestinal ulcers, hepatic toxicity, Steven Johnson syndrome, respiratory skin rashes, acute exacerbation of asthma and anaphylaxis. We have reported here severe distress hypersensitive reaction with ibuprofen induced hypersensitivity syndrome. Within two hours of consumption of ibuprofen patient developed severe bronchospasm, throat and laryngeal oedema leading to respiratory distress. He was treated with salbutamol, hydrocortisone, deriphylline and supportive oxygen, but did not respond and went into coma. Unlike acetaminophen, ibuprofen does not have any antidote hence managing adverse drug reactions (ADR due to ibuprofen is big challenge. Therefore understanding pathophysiology of ADR to Ibuprofen is necessary to manage the patient. Literature in the field of allergic drug reaction shows that epinephrine, a physiological antagonist of histamine is the first drug of choice for the treatment of allergic or drug induced angioedema, laryngeal oedema and bronchospasm due to its direct action on target organs. Such reactions should therefore be managed by epinephrine without loss of time. ADR due to ibuprofen could be prevented by (a avoiding unnecessary intake of drug, (b educating patients / families and public about adverse drug reactions (c surveillance and monitoring of drug reactions (d record keeping (e drug audit and (f reporting of ADR to state/central pharmacovigilance agency. We do observe doctors having misconception about adrenaline, its actions, usage and side effects especially cardio-vascular, hence are reluctant to use. But in severe violent adverse drug reaction we have to use our wisdom and judgement

  16. Physiological remodelling of the maternal uterine circulation during pregnancy.

    Science.gov (United States)

    Mandala, Maurizio; Osol, George

    2012-01-01

    Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodelling of the entire maternal uterine vasculature. The main focus of this MiniReview is to provide information on upstream (pre-placental) maternal uterine vascular remodelling that facilitates gestational increases in uterine blood flow. Consideration of the three-dimensional pattern of remodelling (circumferential enlargement versus axial elongation), changes in vessel biomechanical properties, and underlying mechanisms [shear stress, nitric oxide, vascular endothelial growth factor (VEGF)/placental growth factor (PlGF), the renin-angiotensin system] and pathways (local versus systemic; venoarterial exchange) are provided using the rat as the principal animal model, although findings from other species are incorporated wherever possible to provide a comparative perspective. The process of maternal gestational uterine vascular remodelling involves a number of cellular processes and mechanisms, including trophoblast invasion, hyperplasia and hypertrophy, and changes in extracellular matrix composition. In addition, changes in cellular function, e.g. the secretory and contractile properties of smooth muscle and an up-regulation of endothelial vasodilatory influences may contribute to uteroplacental blood flow increases through changes in tone as well as in structure. Future studies aimed at better understanding the inter-relationship between changes in vessel structure (remodelling) and function (reactivity) would likely generate new mechanistic insights into the fascinating process of maternal gestational uterine vascular adaptation and provide a more physiological perspective of the underlying cellular processes involved in its regulation.

  17. Unremodeled and remodeled cardiolipin are functionally indistinguishable in yeast.

    Science.gov (United States)

    Baile, Matthew G; Sathappa, Murugappan; Lu, Ya-Wen; Pryce, Erin; Whited, Kevin; McCaffery, J Michael; Han, Xianlin; Alder, Nathan N; Claypool, Steven M

    2014-01-17

    After biosynthesis, an evolutionarily conserved acyl chain remodeling process generates a final highly homogeneous and yet tissue-specific molecular form of the mitochondrial lipid cardiolipin. Hence, cardiolipin molecules in different organisms, and even different tissues within the same organism, contain a distinct collection of attached acyl chains. This observation is the basis for the widely accepted paradigm that the acyl chain composition of cardiolipin is matched to the unique mitochondrial demands of a tissue. For this hypothesis to be correct, cardiolipin molecules with different acyl chain compositions should have distinct functional capacities, and cardiolipin that has been remodeled should promote cardiolipin-dependent mitochondrial processes better than its unremodeled form. However, functional disparities between different molecular forms of cardiolipin have never been established. Here, we interrogate this simple but crucial prediction utilizing the best available model to do so, Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and remodeled cardiolipin, which differ markedly in their acyl chain composition, to support mitochondrial activities known to require cardiolipin. Surprisingly, defined changes in the acyl chain composition of cardiolipin do not alter either mitochondrial morphology or oxidative phosphorylation. Importantly, preventing cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the causative gene in Barth syndrome, ameliorates mitochondrial dysfunction. Thus, our data do not support the prevailing hypothesis that unremodeled cardiolipin is functionally distinct from remodeled cardiolipin, at least for the functions examined, suggesting alternative physiological roles for this conserved pathway.

  18. Unremodeled and Remodeled Cardiolipin Are Functionally Indistinguishable in Yeast*

    Science.gov (United States)

    Baile, Matthew G.; Sathappa, Murugappan; Lu, Ya-Wen; Pryce, Erin; Whited, Kevin; McCaffery, J. Michael; Han, Xianlin; Alder, Nathan N.; Claypool, Steven M.

    2014-01-01

    After biosynthesis, an evolutionarily conserved acyl chain remodeling process generates a final highly homogeneous and yet tissue-specific molecular form of the mitochondrial lipid cardiolipin. Hence, cardiolipin molecules in different organisms, and even different tissues within the same organism, contain a distinct collection of attached acyl chains. This observation is the basis for the widely accepted paradigm that the acyl chain composition of cardiolipin is matched to the unique mitochondrial demands of a tissue. For this hypothesis to be correct, cardiolipin molecules with different acyl chain compositions should have distinct functional capacities, and cardiolipin that has been remodeled should promote cardiolipin-dependent mitochondrial processes better than its unremodeled form. However, functional disparities between different molecular forms of cardiolipin have never been established. Here, we interrogate this simple but crucial prediction utilizing the best available model to do so, Saccharomyces cerevisiae. Specifically, we compare the ability of unremodeled and remodeled cardiolipin, which differ markedly in their acyl chain composition, to support mitochondrial activities known to require cardiolipin. Surprisingly, defined changes in the acyl chain composition of cardiolipin do not alter either mitochondrial morphology or oxidative phosphorylation. Importantly, preventing cardiolipin remodeling initiation in yeast lacking TAZ1, an ortholog of the causative gene in Barth syndrome, ameliorates mitochondrial dysfunction. Thus, our data do not support the prevailing hypothesis that unremodeled cardiolipin is functionally distinct from remodeled cardiolipin, at least for the functions examined, suggesting alternative physiological roles for this conserved pathway. PMID:24285538

  19. Wall tissue remodeling regulates longitudinal tension in arteries.

    Science.gov (United States)

    Jackson, Zane S; Gotlieb, Avrum I; Langille, B Lowell

    2002-05-03

    Changes in blood pressure or flow induce arterial remodeling that normalizes mechanical loads that are imposed on arterial tissue. Arteries are also under substantial longitudinal stretch (axial strain) that may be altered by growth or atrophy of tissues to which they are attached. We therefore tested whether axial strain is also regulated in a negative feedback manner through arterial remodeling. Axial strain in rabbit carotid arteries was increased from 62+/-2% to 97+/-2% without altering other mechanical loads on wall tissues. Strain was reduced within 3 days and completely normalized by 7 days. Remodeling involved tissue elaboration, endothelial cell replication rates were increased by >50-fold and smooth muscle cell replication rates were increased by >15-fold, and substantially elevated DNA, elastin, and collagen contents were recorded. Also, increased rates of apoptosis were indicated by degradation of DNA into oligonucleosomes, and matrix remodeling was reflected in enlarged fenestrae in the internal elastic lamina and increased expression and activation of gelatinases, especially matrix metalloproteinase-2. Intriguingly, reduced axial strain was not normalized, presumably because remodeling processes, apart from cell contraction, are ineffective in decreasing strain, and arterial smooth muscle orientation precludes large effects of contraction on axial strain.

  20. Experimental study on aortic remodeling in sinoaortic denervated rats

    Institute of Scientific and Technical Information of China (English)

    MIAO Chao-yu; TAO Xia; GUAN Yun-feng; YANG You-cai; CHU Zheng-xu; SU Ding-feng

    2001-01-01

    Objective: To study the aortic remodeling produced by chronic sinoaortic denervation (SAD) and its time course, and to study the role of humoral factor in the SAD-induced aortic remodeling. Methods: In rats with chronic SAD or sham operation, the aortic structure was measured by computer-assisted image analysis, the aortic function by isolated artery preparation, and angiotensin Ⅱ concentration by radioimmunoassay. Results and Conclusion: The aortic structural remodeling developed progressively at 4, 8, 16 and 32 weeks after SAD. Aortic structural remodeling after SAD expressed mainly as aortic hypertrophy due to SMC growth and collagen accumulation. The aortic contraction elicited by norepinephrine (NE) was progressively increased 8, 16 and 32 weeks after SAD. The aortic relaxation elicited by acetylcholine (ACh) was depressed 8, 16 and 32 weeks after SAD. In addition, in 32-week SAD rats the NE-induced contraction was not increased by endothelial denudation. These indicated that the increased contraction and depressed relaxation after SAD were related to the change of endothelium and/or the change of interaction between endothelium and SMC. In 10-week SAD rats, plasma angiotensin Ⅱ concentration remained unchanged, whereas aortic angiotensin Ⅱ concentration was significantly increased, suggesting that activation of tissue renin-angiotensin system may be involved in SAD-induced aortic remodeling.

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

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    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.

  2. Therapeutic applications of circadian rhythms for the cardiovascular system

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    Elena V Tsimakouridze

    2015-04-01

    Full Text Available The cardiovascular system exhibits dramatic time-of-day dependent rhythms, for example the diurnal variation of heart rate, blood pressure, and timing of onset of adverse cardiovascular events such as heart attack and sudden cardiac death. Over the past decade, the circadian clock mechanism has emerged as a crucial factor regulating these daily fluctuations. Most recently, these studies have led to a growing clinical appreciation that targeting circadian biology offers a novel therapeutic approach towards cardiovascular (and other diseases. Here we describe leading-edge therapeutic applications of circadian biology including 1 timing of therapy to maximize efficacy in treating heart disease (chronotherapy; 2 novel biomarkers discovered by testing for genomic, proteomic, metabolomic or other factors at different times of day and night (chronobiomarkers; and 3 novel pharmacologic compounds that target the circadian mechanism with potential clinical applications (new chronobiology drugs. Cardiovascular disease remains a leading cause of death worldwide and new approaches in the management and treatment of heart disease are clearly warranted and can benefit patients clinically.

  3. Alcohol consumption, cardiovascular health, and endothelial function markers.

    Science.gov (United States)

    Bau, Paulo F D; Bau, Claiton H D; Rosito, Guido A; Manfroi, Waldomiro C; Fuchs, Flávio D

    2007-11-01

    Cardiovascular diseases are among the worldwide leading causes of shorter life expectancy and loss of quality of life. Thus, any influence of diet or life habits on the cardiovascular system may have important implications for public health. Most world populations consume alcoholic beverages. Since alcohol may have both protective and harmful effects on cardiovascular health, the identification of biochemical mechanisms that could explain such paradoxical effects is warranted. The vascular endothelium is the target of important mediating pathways of differential ethanol concentrations, such as oxidative stress, lipoproteins, and insulin resistance. Alcohol-induced endothelial damage or protection may be related to the synthesis or action of several markers, such as nitric oxide, cortisol, endothelin-1, adhesion molecules, tumor necrosis factor alpha, interleukin-6, C-reactive protein, and haemostatic factors. The expression of these markers is consistent with the J-shaped curve between alcohol consumption and cardiovascular health. However, there is genetic and phenotypic heterogeneity in alcohol response, and despite the apparent beneficial biochemical effects of low doses of ethanol, there is not enough clinical and epidemiological evidence to allow the recommendation to consume alcoholic beverages for abstemious individuals. Considering the potential for addiction of alcoholic beverage consumption and other negative consequences of alcohol, it would be worthwhile to identify substances able to mimic the beneficial effects of low doses of ethanol without its adverse effects.

  4. Cardiovascular effects of radiotherapy on the patient with cancer

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Leonardo Augusto Robert; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade, E-mail: wolney_martins@hotmail.com [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil)

    2016-03-15

    The incidence of cancer (CA) has increased globally and radiotherapy (RT) is a vital component in its treatment. Cardiovascular injuries induced by RT in the treatment of thoracic and cervical CA have been causing problems in clinical practice for decades, and are among the most serious adverse effects of radiation experienced by the growing number of cancer survivors. This article presents a review on the Lilacs, Scielo and Pubmed databases of the main cardiovascular injuries, their mechanisms, clinical presentations, treatments and prevention proposals. Injuries caused by RT include diseases of the pericardium, coronary artery disease, valvular disease, myocardial disease with systolic and diastolic dysfunction, conduction disorders, and carotid artery and great vessels disease. Thoracic and cervical irradiation increases cardiovascular morbidity and mortality. Despite the great progress in the improvement of RT techniques, totally excluding prime areas of the cardiovascular system from the irradiation field is not yet possible. Guidelines must be created for monitoring, diagnosis and treatment of patients with CA treated with RT. (author)

  5. Undergraduates' understanding of cardiovascular phenomena.

    Science.gov (United States)

    Michael, Joel A; Wenderoth, Mary Pat; Modell, Harold I; Cliff, William; Horwitz, Barbara; McHale, Philip; Richardson, Daniel; Silverthorn, Dee; Williams, Stephen; Whitescarver, Shirley

    2002-12-01

    Undergraduates students in 12 courses at 8 different institutions were surveyed to determine the prevalence of 13 different misconceptions (conceptual difficulties) about cardiovascular function. The prevalence of these misconceptions ranged from 20 to 81% and, for each misconception, was consistent across the different student populations. We also obtained explanations for the students' answers either as free responses or with follow-up multiple-choice questions. These results suggest that students have a number of underlying conceptual difficulties about cardiovascular phenomena. One possible source of some misconceptions is the students' inability to apply simple general models to specific cardiovascular phenomena. Some implications of these results for teachers of physiology are discussed.

  6. Fish cardiovascular physiology and disease.

    Science.gov (United States)

    Sherrill, Johanna; Weber, E Scott; Marty, Gary D; Hernandez-Divers, Stephen

    2009-01-01

    Fish patients with cardiovascular disorders present a challenge in terms of diagnostic evaluation and therapeutic options. Veterinarians can approach these cases in fish using methods similar to those employed for other companion animals. Clinicians who evaluate and treat fish in private, aquarium, zoologic, or aquaculture settings need to rely on sound clinical judgment after thorough historical and physical evaluation. Pharmacokinetic data and treatments specific to cardiovascular disease in fish are limited; thus, drug types and dosages used in fish are largely empiric. Fish cardiovascular anatomy, physiology, diagnostic evaluation, monitoring, common diseases, cardiac pathologic conditions, formulary options, and comprehensive references are presented with the goal of providing fish veterinarians with clinically relevant tools.

  7. Molecular mechanism of vitamin D in the cardiovascular system.

    Science.gov (United States)

    Li, Yan Chun

    2011-08-01

    Vitamin D deficiency is a global health problem that has various adverse consequences. Vitamin D is mainly synthesized in the skin by sunlight (UV light) irradiation; therefore, vitamin D status is influenced by geographic locations, seasonal changes, and skin pigmentations. The kidney is involved in the biosynthesis of 1,25-dihydroxyvitamin D and the reuptake of filtered 25-hydroxyvitamin D from the proximal tubules, thus, vitamin D deficiency is highly prevalent in patients with kidney disease who have renal insufficiency. There is a growing body of epidemiological and clinical evidence in the literature that links vitamin D deficiency to cardiovascular disease. The discovery of the vitamin D hormone functioning as an endocrine inhibitor of the renin-angiotensin system provides an explanation for this association. This review will discuss the mechanism underlying the connection between vitamin D and cardiovascular disease and its physiological and therapeutic implications.

  8. Erectile Dysfunction and Hypertension: Impact on Cardiovascular Risk and Treatment

    Directory of Open Access Journals (Sweden)

    Valter Javaroni

    2012-01-01

    Full Text Available Erectile dysfunction (ED is a common complaint in hypertensive men and can represent a systemic vascular disease, an adverse effect of antihypertensive medication or a frequent concern that may impair drug compliance. ED has been considered an early marker of cardiovascular disease. The connection between both conditions seems to be located in the endothelium, which may become unable to generate the necessary dilatation in penile vascular bed in response to sexual excitement, producing persistent impairment in erection. On the other hand, the real influence of antihypertensive drugs in erectile function still deserves discussion. Therefore, regardless of ED mechanism in hypertension, early diagnosis and correct approach of sexual life represent an important step of cardiovascular evaluation which certainly contributes for a better choice of hypertension treatment, preventing some complications and restoring the quality of life.

  9. VASCULAR REMODELING IN HYPERTENSION: ANGIOGENESIS FEATURES

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    L. A. Haisheva

    2014-07-01

    Full Text Available Aim — cross-sectional study of changes in various segments of the vascular bed in arterial hypertension (AH, defining the role of inducers and inhibitors of angiogenesis in these processes.Materials and methods. The study included 99 patients with arterial hypertension of I–II degree, average age of 63.2 ± 2.6 years, diseaseduration 9.2 ± 7.2 years.Results. It was found that patients with arterial hypertension have disorders in all segments of vascular bed: endothelial dysfunction (highvWF, microcirculatory disorders, and increased pulse wave velocity (PWV of elastic-type vessels. The level of angioginesis factors doesnot depend on such parameters as gender, age, body mass index. Smoking and duration of hypertension influence on vascular endothelialgrowth factor raise and endostatin levels are higher in patients with family history of cardiovascular diseases. Duration of disease is directlycorrelated with microcirculatory disorders and the PWV, correlation between microcirculatory disorders and pulse wave velocity indicatetheir common processes.

  10. Gender difference in ventricular response to aortic stenosis: insight from cardiovascular magnetic resonance.

    Directory of Open Access Journals (Sweden)

    Joo Myung Lee

    Full Text Available Although left ventricular hypertrophy (LVH and remodeling is associated with cardiac mortality and morbidity, little is known about the impact of gender on the ventricular response in aortic stenosis (AS patients. This study aimed to analyze the differential effect of gender on ventricular remodeling in moderate to severe AS patients.A total of 118 consecutive patients (67±9 years; 63 males with moderate or severe AS (severe 81.4% underwent transthoracic echocardiography and cardiovascular magnetic resonance (CMR within a 1-month period in this two-center prospective registry. The pattern of LV remodeling was assessed using the LV mass index (LVMI and LV remodeling index (LVRI; LV mass/LV end-diastolic volume by CMR. Although there were no differences in AS severity parameters nor baseline characteristics between genders, males showed a significantly higher LVMI (102.6±29.1 g/m2 vs. 86.1±29.2 g/m2, p=0.003 and LVRI (1.1±0.2 vs. 1.0±0.3, p=0.018, regardless of AS severity. The LVMI was significantly associated with aortic valve area (AVA index and valvuloarterial impedance in females, whereas it was not in males, resulting in significant interaction between genders (PInteraction=0.007/0.014 for AVA index/valvuloarterial impedance, respectively. Similarly, the LVRI also showed a significantly different association between male and female subjects with the change in AS severity parameters (PInteraction=0.033/<0.001/0.029 for AVA index/transaortic mean pressure gradient/valvuloarterial impedance, respectively.Males are associated with greater degree of LVH and higher LVRI compared to females at moderate to severe AS. However, females showed a more exaggerated LV remodeling response, with increased severity of AS and hemodynamic loads, than males.

  11. Hormonal contraception and risk of cardiovascular disease. An international perspective.

    Science.gov (United States)

    Farley, T M; Collins, J; Schlesselman, J J

    1998-03-01

    The most frequent major adverse effect of hormonal contraception is an increased risk of cardiovascular disease. The effect on the risk of venous thromboembolism (VTE), ischemic and hemorrhagic stroke, and myocardial infarction (MI) differs and is strongly influenced by smoking and the presence of other cardiovascular risks factors, such as hypertension and diabetes mellitus. The incidence of each disease rises with age and there are differences in risk among hormonal contraceptive preparations. This article provides a framework within which to assess the balance of risks among types of hormonal contraceptives according to individual circumstances. Data on cardiovascular disease mortality rates in women of reproductive age in different countries of the world were compiled from nationally reported statistics and supplemented where possible with reported disease incidence rates. Risks associated with current use of hormonal contraception were compiled from the most recent publications on the cardiovascular effects of steroid hormone contraception. These were combined to estimate the total cardiovascular incidence and mortality according to baseline cardiovascular risk and individual characteristics. Mortality rates for cardiovascular diseases are very low in women of reproductive age. Myocardial infarction mortality rates rise from mortality rates similarly rise steeply with age and are between 3 and 5 times higher than those for MI. VTE mortality rates rise less steeply with age and are approximately one-tenth the MI mortality rates at age 35-44 years. The adverse effect of oral contraceptives (OC) on the risk of VTE is the most important contributor to the total number of cardiovascular cases attributable to OC use. The increased risk of stroke and MI dominate the patterns of mortality in OC users and smokers. The additional risks attributable to smoking are greater than the additional risks attributable to OC use. The risk attributable to OC use in women mortality

  12. S-nitrosylation of cofilin-1 mediates estradiol-17β-stimulated endothelial cytoskeleton remodeling.

    Science.gov (United States)

    Zhang, Hong-hai; Lechuga, Thomas J; Tith, Tevy; Wang, Wen; Wing, Deborah A; Chen, Dong-bao

    2015-03-01

    Rapid nitric oxide (NO) production via endothelial NO synthase (eNOS) activation represents a major signaling pathway for the cardiovascular protective effects of estrogens; however, the pathways after NO biosynthesis that estrogens use to function remain largely unknown. Covalent adduction of a NO moiety to cysteines, termed S-nitrosylation (SNO), has emerged as a key route for NO to directly regulate protein function. Cofilin-1 (CFL1) is a small actin-binding protein essential for actin dynamics and cytoskeleton remodeling. Despite being identified as a major SNO protein in endothelial cells, whether SNO regulates CFL-1 function is unknown. We hypothesized that estradiol-17β (E2β) stimulates SNO of CFL1 via eNOS-derived NO and that E2β-induced SNO-CFL1 mediates cytoskeleton remodeling in endothelial cells. Point mutation studies determined Cys80 as the primary SNO site among the 4 cysteines (Cys39/80/139/147) in CFL1. Substitutions of Cys80 with Ala or Ser were used to prepare the SNO-mimetic/deficient (C80A/S) CFL1 mutants. Recombinant wild-type (wt) and mutant CFL1 proteins were prepared; their actin-severing activity was determined by real-time fluorescence imaging analysis. The activity of C80A CFL1 was enhanced to that of the constitutively active S3/A CFL1, whereas the other mutants had no effects. C80A/S mutations lowered Ser3 phosphorylation. Treatment with E2β increased filamentous (F)-actin and filopodium formation in endothelial cells, which were significantly reduced in cells overexpressing wt-CFL. Overexpression of C80A, but not C80S, CFL1 decreased basal F-actin and further suppressed E2β-induced F-actin and filopodium formation compared with wt-CFL1 overexpression. Thus, SNO(Cys80) of cofilin-1 via eNOS-derived NO provides a novel pathway for mediating estrogen-induced endothelial cell cytoskeleton remodeling.

  13. Roles and mechanisms of ginsenoside in cardiovascular diseases: progress and perspectives.

    Science.gov (United States)

    Sun, Yingying; Liu, Yue; Chen, Keji

    2016-03-01

    Ginseng is among the oldest traditional Chinese medicinal herbs and is widely used in China and Southeast Asia. Over the past 50 years, considerable research has focused on the chemical constituents, pharmacological action, and clinical applications of ginseng. In this review, we examine the current state of research on ginseng, including the main active ingredient ginsenoside, its pharmacological effects on the cardiovascular system, and mechanisms of action. We focus on what is known of the effects of ginseng against atherosclerosis, arrhythmia, myocardial ischemia, and its inhibition of ventricular remodeling, providing a basis for expanding the clinical applications of ginseng.

  14. Cardiovascular magnetic resonance imaging assessment of outcomes in acute myocardial infarction

    Science.gov (United States)

    Khan, Jamal N; McCann, Gerry P

    2017-01-01

    Cardiovascular magnetic resonance (CMR) imaging uniquely characterizes myocardial and microvascular injury in acute myocardial infarction (AMI), providing powerful surrogate markers of outcomes. The last 10 years have seen an exponential increase in AMI studies utilizing CMR based endpoints. This article provides a contemporary, comprehensive review of the powerful role of CMR imaging in the assessment of outcomes in AMI. The theory, assessment techniques, chronology, importance in predicting left ventricular function and remodelling, and prognostic value of each CMR surrogate marker is described in detail. Major studies illustrating the importance of the markers are summarized, providing an up to date review of the literature base in CMR imaging in AMI. PMID:28289525

  15. [Allergies and adverse events associated with fluoroquinolones].

    Science.gov (United States)

    Muller, Y; Andrey, D; Emonet, S; Harr, T; Spoerl, D

    2015-04-08

    The prescription ot fluoroquinolones has been constantly increasing over the past decade. consequently, an increasing number of hyper-sensitivity reactions and adverse events have been reported. The aim of the review is to discuss the incidence of hypersensitivity reactions either IgE (immediate) or T cells mediated (delayed). We will make an overview ofthe diagnostic tools available to detect such hypersensitivity reactions. Finally, the specific adverse events associated with fluoroquinolones, including tendinopathy, chondrotoxicity, peripheral neuropathy or retinal detachment will be discussed.

  16. Carotenoids and cardiovascular health.

    Science.gov (United States)

    Voutilainen, Sari; Nurmi, Tarja; Mursu, Jaakko; Rissanen, Tiina H

    2006-06-01

    Cardiovascular disease (CVD) is the main cause of death in Western countries. Nutrition has a significant role in the prevention of many chronic diseases such as CVD, cancers, and degenerative brain diseases. The major risk and protective factors in the diet are well recognized, but interesting new candidates continue to appear. It is well known that a greater intake of fruit and vegetables can help prevent heart diseases and mortality. Because fruit, berries, and vegetables are chemically complex foods, it is difficult to pinpoint any single nutrient that contributes the most to the cardioprotective effects. Several potential components that are found in fruit, berries, and vegetables are probably involved in the protective effects against CVD. Potential beneficial substances include antioxidant vitamins, folate, fiber, and potassium. Antioxidant compounds found in fruit and vegetables, such as vitamin C, carotenoids, and flavonoids, may influence the risk of CVD by preventing the oxidation of cholesterol in arteries. In this review, the role of main dietary carotenoids, ie, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin, lutein, and zeaxanthin, in the prevention of heart diseases is discussed. Although it is clear that a higher intake of fruit and vegetables can help prevent the morbidity and mortality associated with heart diseases, more information is needed to ascertain the association between the intake of single nutrients, such as carotenoids, and the risk of CVD. Currently, the consumption of carotenoids in pharmaceutical forms for the treatment or prevention of heart diseases cannot be recommended.

  17. Links between Vitamin D Deficiency and Cardiovascular Diseases.

    Science.gov (United States)

    Mozos, Ioana; Marginean, Otilia

    2015-01-01

    The aim of the present paper was to review the most important mechanisms explaining the possible association of vitamin D deficiency and cardiovascular diseases, focusing on recent experimental and clinical data. Low vitamin D levels favor atherosclerosis enabling vascular inflammation, endothelial dysfunction, formation of foam cells, and proliferation of smooth muscle cells. The antihypertensive properties of vitamin D include suppression of the renin-angiotensin-aldosterone system, renoprotective effects, direct effects on endothelial cells and calcium metabolism, inhibition of growth of vascular smooth muscle cells, prevention of secondary hyperparathyroidism, and beneficial effects on cardiovascular risk factors. Vitamin D is also involved in glycemic control, lipid metabolism, insulin secretion, and sensitivity, explaining the association between vitamin D deficiency and metabolic syndrome. Vitamin D deficit was associated in some studies with the number of affected coronary arteries, postinfarction complications, inflammatory cytokines and cardiac remodeling in patients with myocardial infarction, direct electromechanical effects and inflammation in atrial fibrillation, and neuroprotective effects in stroke. In peripheral arterial disease, vitamin D status was related to the decline of the functional performance, severity, atherosclerosis and inflammatory markers, arterial stiffness, vascular calcifications, and arterial aging. Vitamin D supplementation should further consider additional factors, such as phosphates, parathormone, renin, and fibroblast growth factor 23 levels.

  18. Links between Vitamin D Deficiency and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available The aim of the present paper was to review the most important mechanisms explaining the possible association of vitamin D deficiency and cardiovascular diseases, focusing on recent experimental and clinical data. Low vitamin D levels favor atherosclerosis enabling vascular inflammation, endothelial dysfunction, formation of foam cells, and proliferation of smooth muscle cells. The antihypertensive properties of vitamin D include suppression of the renin-angiotensin-aldosterone system, renoprotective effects, direct effects on endothelial cells and calcium metabolism, inhibition of growth of vascular smooth muscle cells, prevention of secondary hyperparathyroidism, and beneficial effects on cardiovascular risk factors. Vitamin D is also involved in glycemic control, lipid metabolism, insulin secretion, and sensitivity, explaining the association between vitamin D deficiency and metabolic syndrome. Vitamin D deficit was associated in some studies with the number of affected coronary arteries, postinfarction complications, inflammatory cytokines and cardiac remodeling in patients with myocardial infarction, direct electromechanical effects and inflammation in atrial fibrillation, and neuroprotective effects in stroke. In peripheral arterial disease, vitamin D status was related to the decline of the functional performance, severity, atherosclerosis and inflammatory markers, arterial stiffness, vascular calcifications, and arterial aging. Vitamin D supplementation should further consider additional factors, such as phosphates, parathormone, renin, and fibroblast growth factor 23 levels.

  19. Neural circuit rewiring: insights from DD synapse remodeling.

    Science.gov (United States)

    Kurup, Naina; Jin, Yishi

    2016-01-01

    Nervous systems exhibit many forms of neuronal plasticity during growth, learning and memory consolidation, as well as in response to injury. Such plasticity can occur across entire nervous systems as with the case of insect metamorphosis, in individual classes of neurons, or even at the level of a single neuron. A striking example of neuronal plasticity in C. elegans is the synaptic rewiring of the GABAergic Dorsal D-type motor neurons during larval development, termed DD remodeling. DD remodeling entails multi-step coordination to concurrently eliminate pre-existing synapses and form new synapses on different neurites, without changing the overall morphology of the neuron. This mini-review focuses on recent advances in understanding the cellular and molecular mechanisms driving DD remodeling.

  20. The Notch pathway: a novel target for myocardial remodelling therapy?

    Science.gov (United States)

    Ferrari, Roberto; Rizzo, Paola

    2014-08-21

    Pathological ventricle remodelling, which follows a cardiac insult, causes heart failure. Despite the existence of multiple pharmaceutical approaches, heart failure is one of the leading causes of death worldwide and there is an urgent need to explore new therapeutic avenues. The Notch pathway is an evolutionary conserved fundamental pathway that regulates cell fate during development as well as throughout postnatal life in self-renewing tissues. In the myocardium, Notch signalling is involved in the modulation of cardiomyocytes survival, cardiac stem cells differentiation, and angiogenesis which are factors known to determine the extent of pathological cardiac remodelling. Modulation of the Notch pathway could become a tool to limit ventricle remodelling and the associated inexorable deterioration of cardiac performance.

  1. Remodeling of legacy systems in health care using UML.

    Science.gov (United States)

    Garde, Sebastian; Knaup, Petra; Herold, Ralf

    2002-01-01

    Research projects in the field of Medical Informatics often involve the development of application systems. Usually they are developed over a longer period of time, so that at a certain point of time a systematically planned reimplementation is necessary. The first step of reimplementation should be a systematic and comprehensive remodeling. When using UML for this task a systematic approach for remodeling activities is missing. Therefore, we developed a method for remodeling of legacy systems (Qumquad) and applied it to DOSPO, a documentation and therapy planning system for pediatric oncology. Qumquad helps to systematically carry out three steps: the modeling of the current actual state of the application system, the systematic identification of weak points and the development of a target concept for reimplementation considering the identified weak points. Results show that this approach is valuable and feasible and could be applied to various application systems in health care.

  2. Chromatin remodeling and cancer, Part I: Covalent histone modifications.

    Science.gov (United States)

    Wang, Gang G; Allis, C David; Chi, Ping

    2007-09-01

    Dynamic chromatin remodeling underlies many, if not all, DNA-templated biological processes, including gene transcription; DNA replication and repair; chromosome condensation; and segregation and apoptosis. Disruption of these processes has been linked to the development and progression of cancer. The mechanisms of dynamic chromatin remodeling include the use of covalent histone modifications, histone variants, ATP-dependent complexes and DNA methylation. Together, these mechanisms impart variation into the chromatin fiber, and this variation gives rise to an 'epigenetic landscape' that extends the biological output of DNA alone. Here, we review recent advances in chromatin remodeling, and pay particular attention to mechanisms that appear to be linked to human cancer. Where possible, we discuss the implications of these advances for disease-management strategies.

  3. Dynamic regulation of transcription factors by nucleosome remodeling.

    Science.gov (United States)

    Li, Ming; Hada, Arjan; Sen, Payel; Olufemi, Lola; Hall, Michael A; Smith, Benjamin Y; Forth, Scott; McKnight, Jeffrey N; Patel, Ashok; Bowman, Gregory D; Bartholomew, Blaine; Wang, Michelle D

    2015-06-05

    The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

  4. Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in trophoblasts.

    Science.gov (United States)

    Wasilewski, Michał; Semenzato, Martina; Rafelski, Susanne M; Robbins, Jennifer; Bakardjiev, Anna I; Scorrano, Luca

    2012-07-10

    During human pregnancy, placental trophoblasts differentiate and syncytialize into syncytiotrophoblasts that sustain progesterone production [1]. This process is accompanied by mitochondrial fragmentation and cristae remodeling [2], two facets of mitochondrial apoptosis, whose molecular mechanisms and functional consequences on steroidogenesis are unclear. Here we show that the mitochondria-shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis. During syncytialization of trophoblast BeWo cells, levels of the profission mitochondria-shaping protein Drp1 increase, and those of Opa1 and mitofusin (Mfn) decrease, leading to mitochondrial fragmentation and cristae remodeling. Manipulation of the levels of Opa1 reveal an inverse relationship with the efficiency of steroidogenesis in trophoblasts and in mouse embryonic fibroblasts where the mitochondrial steroidogenetic pathway has been engineered. In an in vitro assay, accumulation of cholesterol is facilitated in the inner membrane of isolated mitochondria lacking Opa1. Thus, Opa1-dependent inner membrane remodeling controls efficiency of steroidogenesis.

  5. Approach to dyslipidemia, lipodystrophy, and cardiovascular risk in patients with HIV infection.

    Science.gov (United States)

    Troll, J Gregory

    2011-02-01

    There is a significant prevalence (20%-80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment-associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed.

  6. Cardiovascular autonomic neuropathy in diabetes

    DEFF Research Database (Denmark)

    Spallone, Vincenza; Ziegler, Dan; Freeman, Roy

    2011-01-01

    in type 2 diabetes. CAN is a risk marker of mortality and cardiovascular morbidity, and possibly a progression promoter of diabetic nephropathy. Criteria for CAN diagnosis and staging are: 1. one abnormal cardio-vagal test identifies possible or early CAN; 2. at least two abnormal cardio-vagal tests....... diagnosis of CAN clinical forms, 2. detection and tailored treatment of CAN clinical correlates (e.g. tachycardia, OH, nondipping, QT interval prolongation), 3. risk stratification for diabetic complications and cardiovascular morbidity and mortality, and 4. modulation of targets of diabetes therapy......Cardiovascular Autonomic Neuropathy (CAN) Subcommittee of Toronto Consensus Panel on Diabetic Neuropathy worked to update CAN guidelines, with regard to epidemiology, clinical impact, diagnosis, usefulness of CAN testing, and management. CAN is the impairment of cardiovascular autonomic control...

  7. Cognitive dysfunction after cardiovascular surgery

    DEFF Research Database (Denmark)

    Funder, K S; Steinmetz, J; Rasmussen, L S

    2009-01-01

    This review describes the incidence, risk factors, and long-term consequences of cognitive dysfunction after cardiovascular surgery. Postoperative cognitive dysfunction (POCD) is increasingly being recognized as an important complication, especially in the elderly. A highly sensitive neuropsychol...

  8. Parallel mechanisms suppress cochlear bone remodeling to protect hearing.

    Science.gov (United States)

    Jáuregui, Emmanuel J; Akil, Omar; Acevedo, Claire; Hall-Glenn, Faith; Tsai, Betty S; Bale, Hrishikesh A; Liebenberg, Ellen; Humphrey, Mary Beth; Ritchie, Robert O; Lustig, Lawrence R; Alliston, Tamara

    2016-08-01

    Bone remodeling, a combination of bone resorption and formation, requires precise regulation of cellular and molecular signaling to maintain proper bone quality. Whereas osteoblasts deposit and osteoclasts resorb bone matrix, osteocytes both dynamically resorb and replace perilacunar bone matrix. Osteocytes secrete proteases like matrix metalloproteinase-13 (MMP13) to maintain the material quality of bone matrix through perilacunar remodeling (PLR). Deregulated bone remodeling impairs bone quality and can compromise hearing since the auditory transduction mechanism is within bone. Understanding the mechanisms regulating cochlear bone provides unique ways to assess bone quality independent of other aspects that contribute to bone mechanical behavior. Cochlear bone is singular in its regulation of remodeling by expressing high levels of osteoprotegerin. Since cochlear bone expresses a key PLR enzyme, MMP13, we examined whether cochlear bone relies on, or is protected from, osteocyte-mediated PLR to maintain hearing and bone quality using a mouse model lacking MMP13 (MMP13(-/-)). We investigated the canalicular network, collagen organization, lacunar volume via micro-computed tomography, and dynamic histomorphometry. Despite finding defects in these hallmarks of PLR in MMP13(-/-) long bones, cochlear bone revealed no differences in these markers, nor hearing loss as measured by auditory brainstem response (ABR) or distortion product oto-acoustic emissions (DPOAEs), between wild type and MMP13(-/-) mice. Dynamic histomorphometry revealed abundant PLR by tibial osteocytes, but near absence in cochlear bone. Cochlear suppression of PLR corresponds to repression of several key PLR genes in the cochlea relative to long bones. These data suggest that cochlear bone uniquely maintains bone quality and hearing independent of MMP13-mediated osteocytic PLR. Furthermore, the cochlea employs parallel mechanisms to inhibit remodeling by osteoclasts and osteoblasts, and by

  9. [Subclinical hypothyroidism and cardiovascular risk].

    Science.gov (United States)

    López Rubio, María Antonia; Tárraga López, Pedro Juan; Rodríguez Montes, José Antonio; Frías López, María del Carmen; Solera Albero, Juan; Bermejo López, Pablo

    2015-05-01

    Objetivos: Valorar si el hipotiroidismo subclínico puede comportarse como un factor de riesgo cardiovascular o un modificador del mismo, identificando variables epidemiológicas y riesgo cardiovascular estimado en una muestra de sujetos diagnosticados en la provincia de Albacete. Método: Estudio observacional, descriptivo y transversal realizado en Albacete durante la primera quincena de enero de 2012 en pacientes de ambos géneros con hipotiroidismo subclínico. Se analizaron las siguientes variables: glucemia basal, colesterol total, colesterol HDL, colesterol LDL, triglicéridos, TSH, T4, peso, talla, I.M.C., tensión arterial, antecedentes de patología cardiovascular, factores de riesgo cardiovascular y riesgo cardiovascular estimado. Resultados: Se obtuvieron 326 pacientes, con predominio femenino (79,2 %), menores de 65 años en el 78% y sin factores de riesgo cardiovascular en el 48,61%. La prevalencia de los factores de riesgo cardiovascular identificados fué: tabaquismo (33,2%), diabetes mellitus (24,9%), hipertensión arterial (23,4%), alteraciones lipídicas (28,9%) y fibrilación auricular (4,9 %). No se encontró asociación entre hipotiroidismo subclínico y la mayoría de los parámetros del perfil lipídico que condicionan un perfil pro-aterogénico, salvo con la hipertrigliceridemia. Asimismo, tampoco se constató asociación con riesgo cardiovascular aumentado. Conclusiones: El perfil del paciente con hipotiroidismo subclínico es una mujer de mediana edad sin factores de riesgo cardiovascular en la mitad de casos. Se ha encontrado relación entre hipotiroidismo subclínico e hipertrigliceridemia, pero no con el resto de parámetros del perfil lipídico, otros factores de riesgo cardiovascular o con aumento de dicho riesgo. Sin embargo, un 25% de diabéticos y un 22% de no diabéticos están en situación de riesgo cardiovascular moderado-alto.

  10. Exercise and the Cardiovascular System

    OpenAIRE

    Saeid Golbidi; Ismail Laher

    2012-01-01

    There are alarming increases in the incidence of obesity, insulin resistance, type II diabetes, and cardiovascular disease. The risk of these diseases is significantly reduced by appropriate lifestyle modifications such as increased physical activity. However, the exact mechanisms by which exercise influences the development and progression of cardiovascular disease are unclear. In this paper we review some important exercise-induced changes in cardiac, vascular, and blood tissues and discuss...

  11. Vitamin D and Cardiovascular Disease

    OpenAIRE

    Vivian Cristina Garcia; Lígia Araújo Martini

    2010-01-01

    Vitamin D insufficiency/deficiency has been observed worldwide at all stages of life. It has been characterized as a public health problem, since low concentrations of this vitamin have been linked to the pathogenesis of several chronic diseases. Several studies have suggested that vitamin D is involved in cardiovascular diseases and have provided evidence that it has a role in reducing cardiovascular disease risk. It may be involved in regulation of gene expression through the presence of vi...

  12. Vitamin D and Cardiovascular Disease

    OpenAIRE

    Grübler, Martin R.; Martin Gaksch; Thomas Pieber; Katharina Kienreich; Nicolas Verheyen; Andreas Tomaschitz; Stefan Pilz

    2013-01-01

    Vitamin D deficiency, as well as cardiovascular diseases (CVD) and related risk factors are highly prevalent worldwide and frequently co-occur. Vitamin D has long been known to be an essential part of bone metabolism, although recent evidence suggests that vitamin D plays a key role in the pathophysiology of other diseases, including CVD, as well. In this review, we aim to summarize the most recent data on the involvement of vitamin D deficiency in the development of major cardiovascular risk...

  13. Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes.

    Science.gov (United States)

    Kones, Richard

    2013-01-01

    Residual risk, the ongoing appreciable risk of major cardiovascular events (MCVE) in statin-treated patients who have achieved evidence-based lipid goals, remains a concern among cardiologists. Factors that contribute to this continuing risk are atherogenic non-low-density lipoprotein (LDL) particles and atherogenic processes unrelated to LDL cholesterol, including other risk factors, the inherent properties of statin drugs, and patient characteristics, ie, genetics and behaviors. In addition, providers, health care systems, the community, public policies, and the environment play a role. Major statin studies suggest an average 28% reduction in LDL cholesterol and a 31% reduction in relative risk, leaving a residual risk of about 69%. Incomplete reductions in risk, and failure to improve conditions that create risk, may result in ongoing progression of atherosclerosis, with new and recurring lesions in original and distant culprit sites, remodeling, arrhythmias, rehospitalizations, invasive procedures, and terminal disability. As a result, identification of additional agents to reduce residual risk, particularly administered together with statin drugs, has been an ongoing quest. The current model of atherosclerosis involves many steps during which disease may progress independently of guideline-defined elevations in LDL cholesterol. Differences in genetic responsiveness to statin therapy, differences in ability of the endothelium to regenerate and repair, and differences in susceptibility to nonlipid risk factors, such as tobacco smoking, hypertension, and molecular changes associated with obesity and diabetes, may all create residual risk. A large number of inflammatory and metabolic processes may also provide eventual therapeutic targets to lower residual risk. Classically, epidemiologic and other evidence suggested that raising high-density lipoprotein (HDL) cholesterol would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL

  14. Instability of trinucleotidic repeats during chromatin remodeling in spermatids.

    Science.gov (United States)

    Simard, Olivier; Grégoire, Marie-Chantal; Arguin, Mélina; Brazeau, Marc-André; Leduc, Frédéric; Marois, Isabelle; Richter, Martin V; Boissonneault, Guylain

    2014-11-01

    Transient DNA breaks and evidence of DNA damage response have recently been reported during the chromatin remodeling process in haploid spermatids, creating a potential window of enhanced genetic instability. We used flow cytometry to achieve separation of differentiating spermatids into four highly purified populations using transgenic mice harboring 160 CAG repeats within exon 1 of the human Huntington disease gene (HTT). Trinucleotic repeat expansion was found to occur immediately following the chromatin remodeling steps, confirming the genetic instability of the process and pointing to the origin of paternal anticipation observed in some trinucleotidic repeats diseases.

  15. Vitamin D and cardiovascular disease.

    Science.gov (United States)

    Norman, P E; Powell, J T

    2014-01-17

    Vitamin D plays a classical hormonal role in skeletal health by regulating calcium and phosphorus metabolism. Vitamin D metabolites also have physiological functions in nonskeletal tissues, where local synthesis influences regulatory pathways via paracrine and autocrine mechanisms. The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D, binds to the vitamin D receptor that regulates numerous genes involved in fundamental processes of potential relevance to cardiovascular disease, including cell proliferation and differentiation, apoptosis, oxidative stress, membrane transport, matrix homeostasis, and cell adhesion. Vitamin D receptors have been found in all the major cardiovascular cell types including cardiomyocytes, arterial wall cells, and immune cells. Experimental studies have established a role for vitamin D metabolites in pathways that are integral to cardiovascular function and disease, including inflammation, thrombosis, and the renin-angiotensin system. Clinical studies have generally demonstrated an independent association between vitamin D deficiency and various manifestations of degenerative cardiovascular disease including vascular calcification. However, the role of vitamin D supplementation in the management of cardiovascular disease remains to be established. This review summarizes the clinical studies showing associations between vitamin D status and cardiovascular disease and the experimental studies that explore the mechanistic basis for these associations.

  16. [Air pollution and cardiovascular disease].

    Science.gov (United States)

    Haber, Guy; Witberg, Guy; Danenberg, Haim

    2007-10-01

    Cardiovascular atherothrombosis is the most common cause of death globally, with several well-known risk factors. Air pollution is a byproduct of fuel combustion by motor vehicles, power plants and industrial factories. It is composed of gases, fluids and particulate matter (PM) of different sizes, which include basic carbon, organic carbonic molecules and metals such as vanadium, nickel, zinc and iron. These particles are subdivided by their median size, a major contributing factor for their capability to enter the human body through the respiratory system. Most of the epidemiological studies have shown correlation between acute and long-term exposure to air pollution elements and cardiovascular morbidity in general, and angina pectoris and acute myocardial infarction specifically. Physiological studies have found different arrhythmias as the etiologic cause of cardiovascular morbidity and mortality following exposure to air pollution. A major finding was a decline in heart rate variability, a phenomenon known as endangering for cardiovascular morbidity and mortality, especially in patients after acute myocardial infarction. To date, several pathways have been proposed, including a hypercoagulable state following an inflammatory response, cardiac nervous autonomic disequilibrium, endothelial dysfunction with blood vessel contraction and direct toxic impact on cardiac muscle. Additional research is needed for clarifying the pathophysiological pathways by which air pollution affects the cardiovascular system. That might allow forthcoming with preventive measures and correct treatment, and hence a decrease in cardiovascular morbidity and mortality. Another important target is dose-outcome correlation curves for safety threshold calculation as a basis for air pollution regulations.

  17. Osteoporosis and ischemic cardiovascular disease.

    Science.gov (United States)

    Laroche, Michel; Pécourneau, Virginie; Blain, Hubert; Breuil, Véronique; Chapurlat, Roland; Cortet, Bernard; Sutter, Bruno; Degboe, Yannick

    2016-11-09

    Osteoporosis and cardiovascular disease were long viewed as independent of each other. However, numerous epidemiological studies, which are discussed in the first part of this review, have provided incontrovertible evidence of a link. Thus, the risk of coronary artery disease and stroke is higher in patients with a history of osteoporotic fracture or low bone mineral density than in non-osteoporotic patients. In the other direction, patients with cardiovascular disease are at higher risk for bone loss and osteoporotic fracture. The link between osteoporosis and cardiovascular disease is due in part to shared conventional risk factors such as estrogen deprivation in women, smoking, low physical activity, and diabetes. In addition, atheroma plaque calcification involves cytokines and growth factors that also play a role in bone turnover, including proinflammatory cytokines (IL-6 and TNFα), osteoprotegerin, sclerostin, matrix GLA protein, and FGF-23. Several recent studies have provided support for these pathophysiological hypotheses. Thus, elevation of osteoprotegerin, sclerostin, or FGF-23 levels may explain and predict the occurrence of both osteoporotic fractures and cardiovascular events. The association between osteoporosis and cardiovascular disease found in most epidemiological and pathophysiological studies suggests a need for evaluating potential benefits from routine bone absorptiometry and osteoporotic fracture detection in patients with cardiovascular disease and from exercise testing and arterial Doppler imaging in patients with osteoporosis.

  18. Metformin and its effects on myocardial dimension and left ventricular hypertrophy in normotensive patients with coronary heart disease (the MET-REMODEL study): rationale and design of the MET-REMODEL study.

    Science.gov (United States)

    Mohan, Mohapradeep; McSwiggan, Stephen; Baig, Fatima; Rutherford, Lynn; Lang, Chim C

    2015-02-01

    Left ventricular hypertrophy (LVH) is a common and independent risk factor for cardiovascular events in patients with coronary artery disease (CAD). Controlling blood pressure is the standard approach to the management of LVH, but this is only partially effective as LVH also persists in normotensive patients. Apart from blood pressure (BP), other main risk factors associated with LVH are insulin resistance (IR) and central obesity. The diabetic medication, Metformin, reduces IR and aids weight loss and may therefore regress LVH. The MET REMODEL study will investigate the ability of Metformin to regress LVH in 64 patients with CAD. The MET-REMODEL trial is a single-center, phase IV, double blind, randomized, placebo-controlled trial to investigate the efficacy of Metformin in regression of the independent cardiac risk factor of LVH in patients with CAD who are insulin resistant. A minimum of 64 adults with a history of CAD with LVH and IR will be randomized into two groups to receive, either Metformin XL or placebo. The primary endpoint of this trial is to investigate any change in left ventricular mass index. Secondary endpoints include changes to insulin resistance measured using fasting insulin resistance index (FIRI), obesity, LV size, and function and improvement in endothelial function. A positive result will assist clinicians to identify a new mechanism for LVH regression by administering Metformin XL. This may also lead to investigating the mortality benefit of Metformin in patients with CAD and LVH.

  19. Childhood adversities and laboratory pain perception

    Directory of Open Access Journals (Sweden)

    Pieritz K

    2015-08-01

    Full Text Available Karoline Pieritz, Winfried Rief, Frank EuteneuerDivision of Clinical Psychology and Psychotherapy, Philipps University Marburg, Marburg, GermanyAbstract: Childhood adversity has frequently been related to a wide range of psychosomatic complaints in adulthood. The present study examined the relationship between different forms of childhood adversity and laboratory measures of pain. Heat pain tolerance and perceived heat pain intensity were measured in a community-based sample of 62 women (aged 20–64 years. Participants completed the Childhood Trauma Questionnaire (CTQ, which assesses five forms of childhood adversity: physical abuse, sexual abuse, emotional abuse, physical neglect, and emotional neglect. Somatic symptoms, depressive symptoms, and pain catastrophizing were assessed as potential mediators. Bivariate analyses indicated that emotional abuse but no other forms of childhood adversity were significantly related to decreased heat pain tolerance (r=-0.27; P<0.05. Accordingly, multiple regression analyses revealed that only emotional abuse was a significant predictor of heat pain tolerance (β=-0.62; P=0.034 when entering all CTQ subscales simultaneously. Although emotional abuse was also related to somatic symptoms, depressive symptoms, and pain catastrophizing, none of these variables mediated the relationship between childhood adversity and laboratory pain (P>0.1. No significant associations were found between any forms of childhood adversity and heat pain intensity. Our findings indicate that the severity of emotional childhood abuse is associated with decreased pain tolerance, an affective component of pain, but not with heat pain intensity, which has been described as a sensory component of pain.Keywords: childhood adversity, emotional abuse, pain tolerance, pain intensity, somatic symptoms

  20. Toll-like receptor modulation in cardiovascular disease: a target for intervention?

    Science.gov (United States)

    Földes, Gábor; von Haehling, Stephan; Anker, Stefan D

    2006-08-01

    Toll-like receptors (TLRs) form a family of pattern recognition receptors that have emerged as key mediators of innate immunity. These receptors sense invading microbes and initiate the immune response. TLR-mediated inflammation is an important pathogenic link between innate immunity and a diverse panel of clinical disorders. Among the processes in which TLRs play a role are cardiovascular disorders such as cardiac ischaemia, coronary artery disease, ventricular remodelling, cancer angiogenesis or transplant rejection. From these, many important opportunities for disease modification through TLR signalling manipulation can be imagined. Their role as potential targets for therapeutic intervention is just beginning to be appreciated and this article reviews the current status of these treatment strategies for cardiovascular disease.

  1. Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice

    Science.gov (United States)

    Dewald, Daniela; Schmitz, Eva J.; Verfuerth, Luise; Keppel, Katharina; Peigney, Christine; Ghanem, Alexander; Welz, Armin; Dewald, Oliver

    2016-01-01

    Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT−/−)-mice (n = 8–10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT−/−-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2−/−-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT−/−-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2−/−-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling. PMID:27403038

  2. Cardiac remodeling associated with protein increase and lipid accumulation in early-stage chronic kidney disease in rats.

    Science.gov (United States)

    Kuwahara, Mieko; Bannai, Kenji; Segawa, Hiroko; Miyamoto, Ken-ichi; Yamato, Hideyuki

    2014-09-01

    Chronic kidney disease (CKD) is associated with increased risks of cardiovascular morbidity and mortality. Cardiac remodeling including myocardial fibrosis and hypertrophy is frequently observed in CKD patients. In this study, we investigate the mechanism involved in cardiac hypertrophy associated with CKD using a rat model, by morphological and chemical component changes of the hypertrophic and non-hypertrophic hearts. Sprague-Dawley rats were 4/5 nephrectomized (Nx) at 11 weeks of age and assigned to no treatment and treatment with AST-120, which was reported to affect the cardiac damage, at 18 weeks of age. At 26 weeks of age, the rats were euthanized under anesthesia, and biochemical tests as well as analysis of cardiac condition were performed by histological and spectrophotometric methods. Cardiac hypertrophy and CKD were observed in 4/5 Nx rats even though vascular calcification and myocardial fibrosis were not detected. The increasing myocardial protein was confirmed in hypertrophic hearts by infrared spectroscopy. The absorption of amide I and other protein bands in hypertrophic hearts increased at the same position as in normal cardiac absorption. Infrared spectra also showed that lipid accumulation was also detected in hypertrophic heart. Conversely, the absorptions of protein were obviously reduced in the myocardium of non-hypertrophic heart with CKD compared to that of hypertrophic heart. The lipid associated absorption was also decreased in non-hypertrophic heart. Our results suggest that cardiac remodeling associated with relatively early-stage CKD may be suppressed by reducing increased myocardial protein and ameliorating cardiac lipid load.

  3. Cardiovascular Risk Factors and Cardiovascular Hyperreactivity in Young Venezuelans

    Directory of Open Access Journals (Sweden)

    Sady Montes Amador

    2015-07-01

    Full Text Available Background: cardiovascular hyperreactivity in young people has been associated with different risk factors and a family history of hypertension. Objective: to determine the association between a family history of hypertension and cardiovascular risk factors with cardiovascular hyperreactivity. Method: a correlational, cross-sectional study was conducted in a universe of 77 young individuals aged 18 to 40 years from the Churuguara parish of the Falcon State in Venezuela. The variables were: age, sex, skin color, family history of hypertension, medical history of hypertension, diabetes mellitus, alcohol consumption, salt intake, physical activity and body mass index. The diastolic and systolic blood pressure before and after the pressor response elicited by an isometric exercise were determined as hemodynamic variables. Results: thirteen percent of the participants developed vascular reactivity after the hand-held weight test. Cardiovascular hyperreactivity is three times higher in individuals with a family history of hypertension. Sixty percent of those with a body mass index greater than or equal to 27 kg/m2 are hyperreactive. There is a higher cardiovascular response to the hand-held weight test as the consumption of alcohol increases. Thirty three point three percent of the participants who smoke are hyperreactive. Conclusions: there is a significant association between a family history of hypertension, obesity, salt intake, alcohol consumption and vascular hyperreactivity.

  4. The complement system and adverse pregnancy outcomes.

    Science.gov (United States)

    Regal, Jean F; Gilbert, Jeffrey S; Burwick, Richard M

    2015-09-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the fetal allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child.

  5. Environmental adversity and uncertainty favour cooperation

    Science.gov (United States)

    Andras, Peter; Lazarus, John; Roberts, Gilbert

    2007-01-01

    Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher) or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies. PMID:18053138

  6. Environmental adversity and uncertainty favour cooperation

    Directory of Open Access Journals (Sweden)

    Lazarus John

    2007-11-01

    Full Text Available Abstract Background A major cornerstone of evolutionary biology theory is the explanation of the emergence of cooperation in communities of selfish individuals. There is an unexplained tendency in the plant and animal world – with examples from alpine plants, worms, fish, mole-rats, monkeys and humans – for cooperation to flourish where the environment is more adverse (harsher or more unpredictable. Results Using mathematical arguments and computer simulations we show that in more adverse environments individuals perceive their resources to be more unpredictable, and that this unpredictability favours cooperation. First we show analytically that in a more adverse environment the individual experiences greater perceived uncertainty. Second we show through a simulation study that more perceived uncertainty implies higher level of cooperation in communities of selfish individuals. Conclusion This study captures the essential features of the natural examples: the positive impact of resource adversity or uncertainty on cooperation. These newly discovered connections between environmental adversity, uncertainty and cooperation help to explain the emergence and evolution of cooperation in animal and human societies.

  7. Putative adverse outcome pathways relevant to neurotoxicity

    Science.gov (United States)

    Bal-Price, Anna; Crofton, Kevin M.; Sachana, Magdalini; Shafer, Timothy J.; Behl, Mamta; Forsby, Anna; Hargreaves, Alan; Landesmann, Brigitte; Lein, Pamela J.; Louisse, Jochem; Monnet-Tschudi, Florianne; Paini, Alicia; Rolaki, Alexandra; Schrattenholz, André; Suñol, Cristina; van Thriel, Christoph; Whelan, Maurice; Fritsche, Ellen

    2016-01-01

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways. PMID:25605028

  8. Screening for cardiovascular safety: a structure-activity approach for guiding lead selection of melanin concentrating hormone receptor 1 antagonists.

    Science.gov (United States)

    Kym, Philip R; Souers, Andrew J; Campbell, Thomas J; Lynch, John K; Judd, Andrew S; Iyengar, Rajesh; Vasudevan, Anil; Gao, Ju; Freeman, Jennifer C; Wodka, Dariusz; Mulhern, Mathew; Zhao, Gang; Wagaw, Seble H; Napier, James J; Brodjian, Sevan; Dayton, Brian D; Reilly, Regina M; Segreti, Jason A; Fryer, Ryan M; Preusser, Lee C; Reinhart, Glenn A; Hernandez, Lisa; Marsh, Kennan C; Sham, Hing L; Collins, Christine A; Polakowski, James S

    2006-04-06

    An inactin-anesthetized rat cardiovascular (CV) assay was employed in a screening mode to triage multiple classes of melanin-concentrating hormone receptor 1 (MCHr1) antagonists. Lead identification was based on a compound profile producing high drug concentration in both plasma (>40 microM) and brain (>20 microg/g) with optimization activities on multiple classes of MCHr1 antagonists were terminated. After providing evidence that the cardiovascular liabilities were not a function of MCHr1 antagonism, continued screening identified the chromone-substituted aminopiperidine amides as a class of MCHr1 antagonists that demonstrated a safe cardiovascular profile at high drug concentrations in both plasma and brain. The high incidence of adverse cardiovascular effects associated with an array of MCHr1 antagonists of significant chemical diversity, combined with the stringent safety requirements for antiobesity drugs, highlight the importance of incorporating cardiovascular safety assessment early in the lead selection process.

  9. Energy Drinks and Their Impact on the Cardiovascular System: Potential Mechanisms.

    Science.gov (United States)

    Grasser, Erik Konrad; Miles-Chan, Jennifer Lynn; Charrière, Nathalie; Loonam, Cathríona R; Dulloo, Abdul G; Montani, Jean-Pierre

    2016-09-01

    Globally, the popularity of energy drinks is steadily increasing. Scientific interest in their effects on cardiovascular and cerebrovascular systems in humans is also expanding and with it comes a growing number of case reports of adverse events associated with energy drinks. The vast majority of studies carried out in the general population report effects on blood pressure and heart rate. However, inconsistencies in the current literature render it difficult to draw firm conclusions with regard to the effects of energy drinks on cardiovascular and cerebrovascular variables. These inconsistencies are due, in part, to differences in methodologies, volume of drink ingested, and duration of postconsumption measurements, as well as subject variables during the test. Recent well-controlled, randomized crossover studies that used continuous beat-to-beat measurements provide evidence that cardiovascular responses to the ingestion of energy drinks are best explained by the actions of caffeine and sugar, with little influence from other ingredients. However, a role for other active constituents, such as taurine and glucuronolactone, cannot be ruled out. This article reviews the potentially adverse hemodynamic effects of energy drinks, particularly on blood pressure and heart rate, and discusses the mechanisms by which their active ingredients may interact to adversely affect the cardiovascular system. Research areas and gaps in the literature are discussed with particular reference to the use of energy drinks among high-risk individuals.

  10. Can experimental data in humans verify the finite element-based bone remodeling algorithm?

    DEFF Research Database (Denmark)

    Wong, Christian; Gehrchen, P Martin; Kiaer, Thomas

    2008-01-01

    A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws.......A finite element analysis-based bone remodeling study in human was conducted in the lumbar spine operated on with pedicle screws. Bone remodeling results were compared to prospective experimental bone mineral content data of patients operated on with pedicle screws....

  11. Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Minicucci, Marcos; Oliveira, Fernando; Santos, Priscila; Polegato, Bertha; Roscani, Meliza; Fernandes, Ana Angelica; Lustosa, Beatriz; Paiva, Sergio; Zornoff, Leonardo; Azevedo, Paula, E-mail: paulasa@fmb.unesp.br [Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, São Paulo, SP (Brazil)

    2016-05-15

    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. The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. 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%. 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. 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.

  12. Airway remodeling: Effect of current and future asthma therapies

    NARCIS (Netherlands)

    Burgess, Janette K.; Moir, Lyn M.

    2007-01-01

    Airway remodeling (the structural changes which occur in the airways) is one of the characteristic features of severe persistent asthma. These changes include thickening of the laminar reticularis, an increase in the bulk of the airway smooth muscle, thickening of the basement membrane and alteratio

  13. Bone remodeling induced by dental implants of functionally graded materials.

    Science.gov (United States)

    Lin, Daniel; Li, Qing; Li, Wei; Swain, Michael

    2010-02-01

    Functionally graded material (FGM) had been developed as a potential implant material to replace titanium for its improved capability of initial osseointegration. The idea behind FGM dental implant is that its properties can be tailored in accordance with the biomechanical needs at different regions adapting to its hosting bony tissues, therefore creating an improved overall integration and stability in the entire restoration. However, there have been very few reports available so far on predicting bone remodeling induced by FGM dental implants. This article aims to evaluate bone remodeling when replacing the titanium with a hydroxyapatite/collagen (HAP/Col) FGM model. A finite element model was constructed in the buccal-lingual section of a dental implant-bone structure generated from in vivo CT scan images. The remodeling simulation was performed over a 4 year healing period. Comparisons were made between the titanium implant and various FGM implants of this model. The FGM implants showed an improved bone remodeling outcome. The study is expected to provide a basis for future development of FGM implants.

  14. Molecular mechanisms of remodeling in human atrial fibrillation

    NARCIS (Netherlands)

    Brundel, BJJM; Henning, RH; Kampinga, HH; Van Gelder, IC; Crijns, HJGM

    2002-01-01

    An important acknowledgement of the last several years is that atrial fibrillation (AF) modifies the electrical properties of the atrium in a way that promotes its occurrence and maintenance. This arrhythmogenic electrophysiological remodeling is well established, but can not explain by itself that

  15. Chromatin remodelers in the DNA double strand break response

    NARCIS (Netherlands)

    Smeenk, Godelieve

    2012-01-01

    During my PhD project, I studied the role of several chromatin remodelers in the DNA double strand break (DSB) response. We discovered that both CHD4 and SMARCA5 are required for ubiquitin signaling through the E3 ubiquitin ligases RNF8 and RNF168, which is a central signaling event in the response

  16. Transcriptional coactivator PGC-1alpha promotes peroxisomal remodeling and biogenesis.

    Science.gov (United States)

    Bagattin, Alessia; Hugendubler, Lynne; Mueller, Elisabetta

    2010-11-23

    Mitochondria and peroxisomes execute some analogous, nonredundant functions including fatty acid oxidation and detoxification of reactive oxygen species, and, in response to select metabolic cues, undergo rapid remodeling and division. Although these organelles share some components of their division machinery, it is not known whether a common regulator coordinates their remodeling and biogenesis. Here we show that in response to thermogenic stimuli, peroxisomes in brown fat tissue (BAT) undergo selective remodeling and expand in number and demonstrate that ectopic expression of the transcriptional coactivator PGC-1α recapitulates these effects on the peroxisomal compartment, both in vitro and in vivo. Conversely, β-adrenergic stimulation of PGC-1α(-/-) cells results in blunted induction of peroxisomal gene expression. Surprisingly, PPARα was not required for the induction of critical biogenesis factors, suggesting that PGC-1α orchestrates peroxisomal remodeling through a PPARα-independent mechanism. Our data suggest that PGC-1α is critical to peroxisomal physiology, establishing a role for this factor as a fundamental orchestrator of cellular adaptation to energy demands.

  17. Is chromatin remodeling required to build sister-chromatid cohesion?

    NARCIS (Netherlands)

    Riedel, Christian G; Gregan, Juraj; Gruber, Stephan; Nasmyth, Kim

    2004-01-01

    Chromosome segregation during mitosis and meiosis depends on the linkage of sister DNA molecules after replication. These links, known as sister-chromatid cohesion, are provided by a multi-subunit complex called cohesin. Recent papers suggest that chromatin-remodeling complexes also have a role in t

  18. Functional Insights into Chromatin Remodelling from Studies on CHARGE Syndrome

    NARCIS (Netherlands)

    Basson, M. Albert; van Ravenswaaij-Arts, Conny

    2015-01-01

    CHARGE syndrome is a rare genetic syndrome characterised by a unique combination of multiple organ anomalies. Dominant loss-of-function mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7), which is an ATP-dependent chromatin remodeller, have been identified as the cause

  19. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    2012-01-01

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an impo

  20. Energy Efficiency Measures to Incorporate into Remodeling Projects

    Energy Technology Data Exchange (ETDEWEB)

    Liaukus, C. [Building America Research Alliance, Kent, WA (United States)

    2014-12-01

    Energy improvements in a home are often approached as one concerted effort, beginning with a simple walk-through assessment or more in-depth energy audit and followed by the installation of recommended energy measures. While this approach allows for systems thinking to guide the efforts, comprehensive energy improvements of this nature are undertaken by a relatively small number of U.S. households compared to piecemeal remodeling efforts. In this report, the U.S Department of Energy Building America Retrofit Alliance research team examines the improvement of a home’s energy performance in an opportunistic way by examining what can be done to incorporate energy efficiency measures into general remodeling work and home repair projects. This allows for energy efficiency upgrades to occur at the same time as remodeling proejcts. There are challenges to this approach, not the least of which being that the work will take place over time in potentially many separate projects. The opportunity to improve a home’s energy efficiency at one time expands or contracts with the scope of the remodel. As such, guidance on how to do each piece thoughtfully and with consideration for potential future projects, is critical.