The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

Science.gov (United States)

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

Science.gov (United States)

Tylutki, Zofia; Polak, Sebastian

2015-03-12

Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Establishing Early Functional Perfusion and Structure in Tissue Engineered Cardiac Constructs.

Science.gov (United States)

Wang, Bo; Patnaik, Sourav S; Brazile, Bryn; Butler, J Ryan; Claude, Andrew; Zhang, Ge; Guan, Jianjun; Hong, Yi; Liao, Jun

2015-01-01

Myocardial infarction (MI) causes massive heart muscle death and remains a leading cause of death in the world. Cardiac tissue engineering aims to replace the infarcted tissues with functional engineered heart muscles or revitalize the infarcted heart by delivering cells, bioactive factors, and/or biomaterials. One major challenge of cardiac tissue engineering and regeneration is the establishment of functional perfusion and structure to achieve timely angiogenesis and effective vascularization, which are essential to the survival of thick implants and the integration of repaired tissue with host heart. In this paper, we review four major approaches to promoting angiogenesis and vascularization in cardiac tissue engineering and regeneration: delivery of pro-angiogenic factors/molecules, direct cell implantation/cell sheet grafting, fabrication of prevascularized cardiac constructs, and the use of bioreactors to promote angiogenesis and vascularization. We further provide a detailed review and discussion on the early perfusion design in nature-derived biomaterials, synthetic biodegradable polymers, tissue-derived acellular scaffolds/whole hearts, and hydrogel derived from extracellular matrix. A better understanding of the current approaches and their advantages, limitations, and hurdles could be useful for developing better materials for future clinical applications.

Experience in procurement and processing of heart valves at the Northwest Tissue Center

International Nuclear Information System (INIS)

Strong, M.; O'Neal, P.D.; Gage, H.N.; Moogk, M.

1999-01-01

The Northwest Tissue Center established a human heart valve program in 199 1. It is one of four non-profit tissue banks and one for-profit program that recover and process heart valves in the United States. During the eight years in which the Northwest Tissue Center has been involved in heart valve banking, there have been a total of 673 hearts procured for processing. The age of the donors ranged from <1 to 44 years with a mean of 26.2 years, 66% werw male,and 6.5% of the hearts procered were discarded due to a variety of medical and criteria reason. The primary reasons for differal were questions of possible cancer and questions of high risk behavior/social history. Of the 1,264 cardiovascular tissues processed, 6% were lost because of donor history, 17% were lost because of microbiology results, and 5% were lost because of donor serology . There were total a total of 190 aortic valves and 48 pulmonic conduits transplanted over this time period. The mean age of the recipients was 23.4 with a median or 23 years; 102 of the recipients were less than one year of age. Males comprised 62% of the recipients. Since 1993, there has been a clear shift towards more use of pulmonic valves over aortic valves as a results of the acceptance of the Ross procedure. Early in the program, reports were received from surgeons that some heart valves appeared to have cracks in the conduits. Experimentations in the laboratory led to the discovery that thawing too rapidly would result in cracking of these materials. Packaging was designed to reduce the rate of thawing and this has resolved the problem with cracking. The heart valve program at the Northwest Tissue Center has been very successful in providing the necessary valves for patients in the Northwest Region of the United States

Quantification of total mercury in liver and heart tissue of Harbor Seals (Phoca vitulina) from Alaska USA

International Nuclear Information System (INIS)

Marino, Kady B.; Hoover-Miller, Anne; Conlon, Suzanne; Prewitt, Jill; O'Shea, Stephen K.

2011-01-01

This study quantified the Hg levels in the liver (n=98) and heart (n=43) tissues of Harbor Seals (Phoca vitulina) (n=102) harvested from Prince William Sound and Kodiak Island Alaska. Mercury tissue dry weight (dw) concentrations in the liver ranged from 1.7 to 393 ppm dw, and in the heart from 0.19 to 4.99 ppm dw. Results of this study indicate liver and heart tissues' Hg ppm dw concentrations significantly increase with age. Male Harbor Seals bioaccumulated Hg in both their liver and heart tissues at a significantly faster rate than females. The liver Hg bioaccumulation rates between the harvest locations Kodiak Island and Prince William Sound were not found to be significantly different. On adsorption Hg is transported throughout the Harbor Seal's body with the partition coefficient higher for the liver than the heart. No significant differences in the bio-distribution (liver:heart Hg ppm dw ratios (n=38)) values were found with respect to either age, sex or geographic harvest location. In this study the age at which Hg liver and heart bioaccumulation levels become significantly distinct in male and female Harbor Seals were identified through a Tukey's analysis. Of notably concern to human health was a male Harbor Seal's liver tissue harvested from Kodiak Island region. Mercury accumulation in this sample tissue was determined through a Q-test to be an outlier, having far higher Hg concentrarion (liver 392 Hg ppm dw) than the general population sampled. - Highlights: ► Mercury accumulation in the liver and heart of seals exceed food safety guidelines. ► Accumulation rate is greater in males than females with age. ► Liver mercury accumulation is greater than in the heart tissues. ► Mercury determination by USA EPA Method 7473 using thermal decomposition.

Fatty acid composition of muscle and heart tissue of Nile perch ...

African Journals Online (AJOL)

The fatty acid composition in the heart tissue and muscle tissue of the Nile perch, Lates niloticus, and Nile tilapia, Oreochromis niloticus populations from Lakes Kioga and Victoria was determined by methanolysis and gas chromatography of the resulting fatty acid methyl esters. The analytical data were treated by ...

High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

International Nuclear Information System (INIS)

Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia; Synnergren, Jane; Johansson, Cecilia Thalén; Palmqvist, Lars; Jeppsson, Anders; Hultén, Lillemor Mattsson

2012-01-01

Highlights: ► We found a 17-fold upregulation of ALOX15 in the ischemic heart. ► Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. ► We observed increased levels of proinflammatory markers in ischemic heart tissue. ► Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1α (HIF-1α) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1α mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield important insights into the underlying association between hypoxia and inflammation in the human ischemic heart disease.

Nondestructive and noninvasive assessment of mechanical properties in heart valve tissue engineering

NARCIS (Netherlands)

Kortsmit, J.; Driessen, N.J.B.; Rutten, M.C.M.; Baaijens, F.P.T.

2009-01-01

Despite recent progress, mechanical behavior of tissue-engineered heart valves still needs improvement when native aortic valves are considered as a benchmark. Although it is known that cyclic straining enhances tissue formation, optimal loading protocols have not been defined yet. To obtain a

A positive perspective of knowledge, attitude, and practices for health-promoting behaviors of adolescents with congenital heart disease.

Science.gov (United States)

Huang, Hui-Ru; Chen, Chi-Wen; Chen, Chin-Mi; Yang, Hsiao-Ling; Su, Wen-Jen; Wang, Jou-Kou; Tsai, Pei-Kwei

2018-03-01

Health-promoting behaviors could serve as a major strategy to optimize long-term outcomes for adolescents with congenital heart disease. The associations assessed from a positive perspective of knowledge, attitudes, and practice model would potentially cultivate health-promoting behaviors during adolescence. The purpose of this study was to examine the relationships between disease knowledge, resilience, family functioning, and health-promoting behaviors in adolescents with congenital heart disease. A total of 320 adolescents with congenital heart disease who were aged 12-18 years were recruited from pediatric cardiology outpatient departments, and participated in a cross-sectional survey. The participants completed the Leuven Knowledge Questionnaire for Congenital Heart Disease; Haase Adolescent Resilience in Illness Scale; Family Adaptability, Partnership, Growth, Affection, and Resolve; and Adolescent Health Promotion scales. The collected data were analyzed using descriptive statistics and three multiple regression models. Greater knowledge of prevention of complications and higher resilience had a more powerful effect in enhancing health-promoting behaviors. Having symptoms and moderate or severe family dysfunction were significantly more negatively predictive of health-promoting behaviors than not having symptoms and positive family function. The third model explained 40% of the variance in engaging in health-promoting behaviors among adolescents with congenital heart disease. The findings of this study provide new insights into the role of disease knowledge, resilience, and family functioning in the health-promoting behavior of adolescents with congenital heart disease. Continued efforts are required to plan family care programs that promote the acquisition of sufficient disease knowledge and the development of resilience for adolescents with congenital heart disease.

Identification, purification, and localization of tissue kallikrein in rat heart.

OpenAIRE

Xiong, W; Chen, L M; Woodley-Miller, C; Simson, J A; Chao, J

1990-01-01

A tissue kallikrein has been isolated from rat heart extracts by DEAE-Sepharose and aprotinin-affinity column chromatography. The purified cardiac enzyme has both N-tosyl-L-arginine methyl ester esterolytic and kinin-releasing activities, and displays parallelism with standard curves in a kallikrein radioimmunoassay, indicating it to have immunological identity with tissue kallikrein. The enzyme is inhibited by aprotinin, antipain, leupeptin and by high concentrations of soybean trypsin inhib...

Building Collaborative Health Promotion Partnerships: The Jackson Heart Study

Directory of Open Access Journals (Sweden)

Clifton C. Addison

2015-12-01

Full Text Available Building Collaborative Health Promotion Partnerships: The Jackson Heart Study. Background: Building a collaborative health promotion partnership that effectively employs principles of community-based participatory research (CBPR involves many dimensions. To ensure that changes would be long-lasting, it is imperative that partnerships be configured to include groups of diverse community representatives who can develop a vision for long-term change. This project sought to enumerate processes used by the Jackson Heart Study (JHS Community Outreach Center (CORC to create strong, viable partnerships that produce lasting change. Methods: JHS CORC joined with community representatives to initiate programs that evolved into comprehensive strategies for addressing health disparities and the high prevalence of cardiovascular disease (CVD. This collaboration was made possible by first promoting an understanding of the need for combined effort, the desire to interact with other community partners, and the vision to establish an effective governance structure. Results: The partnership between JHS CORC and the community has empowered and inspired community members to provide leadership to other health promotion projects. Conclusion: Academic institutions must reach out to local community groups and together address local health issues that affect the community. When a community understands the need for change to respond to negative health conditions, formalizing this type of collaboration is a step in the right direction.

Tissue specific phosphorylation of mitochondrial proteins isolated from rat liver, heart muscle, and skeletal muscle

DEFF Research Database (Denmark)

Bak, Steffen; León, Ileana R; Jensen, Ole Nørregaard

2013-01-01

-specific phosphorylation sites were identified in tissue-specific enzymes such as those encoded by HMGCS2, BDH1, PCK2, CPS1, and OTC in liver mitochondria, and CKMT2 and CPT1B in heart and skeletal muscle. Kinase prediction showed an important role for PKA and PKC in all tissues but also for proline-directed kinases......Phosphorylation of mitochondrial proteins in a variety of biological processes is increasingly being recognized and may contribute to the differences in function and energy demands observed in mitochondria from different tissues such as liver, heart, and skeletal muscle. Here, we used a combination...... of TiO2 phosphopeptide-enrichment, HILIC fractionation, and LC-MS/MS on isolated mitochondria to investigate the tissue-specific mitochondrial phosphoproteomes of rat liver, heart, and skeletal muscle. In total, we identified 899 phosphorylation sites in 354 different mitochondrial proteins including...

Public awareness in promotion of tissue transplantation in Malaysia

International Nuclear Information System (INIS)

Abd Rani Samsudin; Hasim Mohammad

1999-01-01

Malaysia is a developing country in South East Asia with a population of 21 million. The population is multiracial, multicultural and multireligion and it is one of the few countries in the world which possess a multicomplexity way of life among its ethnic groups. The health care system in Malaysia is divided into two main system, i.e. government based or public service and private based health care practice. The idea about organ donation and transplant science has a rise in Malaysia some 30 years ago, and the first historical event of a kidney transplant from a cadaveric donor took place in 1976. 22 years down the line, the first heart transplant was performed in Malaysia. Over the last 22 years between 1976 and 1998 many programmes promoting the idea of organ and tissue transplantation has been came out throughout the country led by government based bodies and non governmental Organisation. In terms of government funding, supporting a transplant programme is not a cheap exercise and this aspect of health care financial burden must be given due consideration by government and non governmental bodies for success of the programme. Besides financial burden, there are the common dilemma of culture and religious barrier for the success of the programme, but this problem has been tackled extremely well by the government. The setting up of two tissue banks in Malaysia in 1991 has further enhanced the idea of organ and tissue transplantation in this country, and the establishment of the national transplant resource centre based at Hospital Kuala Lumpur provides a national coordination service system for both organ and tissue procurement services for the whole country. Organ and tissue donation programme-ne and finally the success of a national transplant programme will certainly depend on the health status and health priorities of the country, the standard of general education, the quality of life style while cultural and religious factors in Malaysia will play a minor

Osseous drill holes to promote granulation tissue: Radiologic appearance

International Nuclear Information System (INIS)

Resnik, C.S.; Reiner, B.I.; Diaconis, J.N.; Goldberg, N.H.

1991-01-01

Skin grafting following extensive soft-tissue loss is often delayed until adequate granulation tissue can be generated. Surgical drill holes into the marrow cavity promote development of granulation tissue. This article illustrates the radiology appearance of these drill holes in four patients. (orig.)

Positional bias of general and tissue-specific regulatory motifs in mouse gene promoters

Directory of Open Access Journals (Sweden)

Farré Domènec

2007-12-01

Full Text Available Abstract Background The arrangement of regulatory motifs in gene promoters, or promoter architecture, is the result of mutation and selection processes that have operated over many millions of years. In mammals, tissue-specific transcriptional regulation is related to the presence of specific protein-interacting DNA motifs in gene promoters. However, little is known about the relative location and spacing of these motifs. To fill this gap, we have performed a systematic search for motifs that show significant bias at specific promoter locations in a large collection of housekeeping and tissue-specific genes. Results We observe that promoters driving housekeeping gene expression are enriched in particular motifs with strong positional bias, such as YY1, which are of little relevance in promoters driving tissue-specific expression. We also identify a large number of motifs that show positional bias in genes expressed in a highly tissue-specific manner. They include well-known tissue-specific motifs, such as HNF1 and HNF4 motifs in liver, kidney and small intestine, or RFX motifs in testis, as well as many potentially novel regulatory motifs. Based on this analysis, we provide predictions for 559 tissue-specific motifs in mouse gene promoters. Conclusion The study shows that motif positional bias is an important feature of mammalian proximal promoters and that it affects both general and tissue-specific motifs. Motif positional constraints define very distinct promoter architectures depending on breadth of expression and type of tissue.

Heart over mind: metabolic control of white adipose tissue and liver.

Science.gov (United States)

Nakamura, Michinari; Sadoshima, Junichi

2014-12-01

Increasing evidence suggests that the heart controls the metabolism of peripheral organs. Olson and colleagues previously demonstrated that miR‐208a controls systemic energy homeostasis through the regulation of MED13 in cardiomyocytes (Grueter et al, 2012). In their follow‐up study in this issue of EMBO Molecular Medicine, white adipose tissue (WAT) and liver are identified as the physiological targets of cardiac MED13 signaling, most likely through cardiac‐derived circulating factors, which boost energy consumption by upregulating metabolic gene expression and increasing mitochondrial numbers (Baskin et al, 2014). In turn, increased energy expenditure in WAT and the liver confers leanness. These findings strengthen the evidence of metabolic crosstalk between the heart and peripheral tissues through cardiokines and also set the stage for the development of novel treatments for metabolic syndrome.

Microarray Expression Profile of Circular RNAs in Heart Tissue of Mice with Myocardial Infarction-Induced Heart Failure

Directory of Open Access Journals (Sweden)

Hong-Jin Wu

2016-06-01

Full Text Available Background/Aims: Myocardial infarction (MI is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. This study is aimed to assess the global changes in and characteristics of the transcriptome of circular RNAs (circRNAs in heart tissue during MI induced heart failure (HF. Methods: Using a post-myocardial infarction (MI model of HF in mice, we applied microarray assay to examine the transcriptome of circRNAs deregulated in the heart during HF. We confirmed the changes in circRNAs by quantitative PCR. Results: We revealed and confirmed a number of circRNAs that were deregulated during HF, which suggests a potential role of circRNAs in HF. Conclusions: The distinct expression patterns of circulatory circRNAs during HF indicate that circRNAs may actively respond to stress and thus serve as biomarkers of HF diagnosis and treatment.

Identification of nodal tissue in the living heart using rapid scanning fiber-optics confocal microscopy and extracellular fluorophores.

Science.gov (United States)

Huang, Chao; Kaza, Aditya K; Hitchcock, Robert W; Sachse, Frank B

2013-09-01

Risks associated with pediatric reconstructive heart surgery include injury of the sinoatrial node (SAN) and atrioventricular node (AVN), requiring cardiac rhythm management using implantable pacemakers. These injuries are the result of difficulties in identifying nodal tissues intraoperatively. Here we describe an approach based on confocal microscopy and extracellular fluorophores to quantify tissue microstructure and identify nodal tissue. Using conventional 3-dimensional confocal microscopy we investigated the microstructural arrangement of SAN, AVN, and atrial working myocardium (AWM) in fixed rat heart. AWM exhibited a regular striated arrangement of the extracellular space. In contrast, SAN and AVN had an irregular, reticulated arrangement. AWM, SAN, and AVN tissues were beneath a thin surface layer of tissue that did not obstruct confocal microscopic imaging. Subsequently, we imaged tissues in living rat hearts with real-time fiber-optics confocal microscopy. Fiber-optics confocal microscopy images resembled images acquired with conventional confocal microscopy. We investigated spatial regularity of tissue microstructure from Fourier analysis and second-order image moments. Fourier analysis of fiber-optics confocal microscopy images showed that the spatial regularity of AWM was greater than that of nodal tissues (37.5 ± 5.0% versus 24.3 ± 3.9% for SAN and 23.8 ± 3.7% for AVN; Pfiber-optics confocal microscopy. Application of the approach in pediatric reconstructive heart surgery may reduce risks of injuring nodal tissues.

Metabolism of 15(p123I iodophenyl-)pentadecanoic acid in heart muscle and noncardiac tissues

International Nuclear Information System (INIS)

Reske, S.N.; Sauer, W.; Winkler, C.; Machulla, H.J.; Knust, J.

1985-01-01

The uptake and turnover of W(p 123 I iodophenyl-)pentadecanoic acid (I-PPA), a radioiodinated free-fatty-acid analog, was examined in the heart, lung, liver, kidneys, spleen, and skeletal muscle of rats. At 2 min post injection, a high cardiac uptake of 4.4% dose per gram had already been achieved; this was followed by a rapid, two-component, tracer clearance. The kinetics of tissue concentrations of labeled hydrophilic catabolites indicated a rapid oxidation of I-PPA and the subsequent washout of I-PPA catabolites from heart-muscle tissue. The fractional distribution of the labeled cardiac lipids compared favorably with previously reported values for 3 H-oleic- or 14 C-palmitic-acid-labeled myocardial lipids. Typical patterns of I-PPA metabolism were observed in tissues; dedpending on primary fatty-acid oxidation, lipid metabolism regulation, or I-PPA-catabolite excretion. The tissue concentrations and kinetics of I-PPA and its metabolites in the heart muscle indicated that general pathways of cardiac-lipid metabolism are traced by this new γ-emitting isotope-labeled radiopharmaceutical. (orig.)

A new construction technique for tissue-engineered heart valves using the self-assembly method.

Science.gov (United States)

Tremblay, Catherine; Ruel, Jean; Bourget, Jean-Michel; Laterreur, Véronique; Vallières, Karine; Tondreau, Maxime Y; Lacroix, Dan; Germain, Lucie; Auger, François A

2014-11-01

Tissue engineering appears as a promising option to create new heart valve substitutes able to overcome the serious drawbacks encountered with mechanical substitutes or tissue valves. The objective of this article is to present the construction method of a new entirely biological stentless aortic valve using the self-assembly method and also a first assessment of its behavior in a bioreactor when exposed to a pulsatile flow. A thick tissue was created by stacking several fibroblast sheets produced with the self-assembly technique. Different sets of custom-made templates were designed to confer to the thick tissue a three-dimensional (3D) shape similar to that of a native aortic valve. The construction of the valve was divided in two sequential steps. The first step was the installation of the thick tissue in a flat preshaping template followed by a 4-week maturation period. The second step was the actual cylindrical 3D forming of the valve. The microscopic tissue structure was assessed using histological cross sections stained with Masson's Trichrome and Picrosirius Red. The thick tissue remained uniformly populated with cells throughout the construction steps and the dense extracellular matrix presented corrugated fibers of collagen. This first prototype of tissue-engineered heart valve was installed in a bioreactor to assess its capacity to sustain a light pulsatile flow at a frequency of 0.5 Hz. Under the light pulsed flow, it was observed that the leaflets opened and closed according to the flow variations. This study demonstrates that the self-assembly method is a viable option for the construction of complex 3D shapes, such as heart valves, with an entirely biological material.

Inducible nitric oxide synthase in heart tissue and nitric oxide in serum of Trypanosoma cruzi-infected rhesus monkeys: association with heart injury.

Directory of Open Access Journals (Sweden)

Cristiano Marcelo Espinola Carvalho

Full Text Available BACKGROUND: The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2 is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2(-/- mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. METHODOLOGY: Rhesus monkeys and C57BL/6 and Nos2(-/- mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2(+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG, echocardiogram (ECHO, creatine kinase heart isoenzyme (CK-MB activity levels in serum and connexin 43 (Cx43 expression in the cardiac tissue. RESULTS: Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC. Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2(+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2(-/- mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. CONCLUSION: T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute

Use of high-dose erythropoietin for repair after injury: A comparison of outcomes in heart and kidney.

Science.gov (United States)

Gobe, Glenda C; Morais, Christudas; Vesey, David A; Johnson, David W

2013-07-01

There is a need to define the exact benefits and contraindications of use of high-dose recombinant human erythropoietin (EPO) for its non-hematopoietic function as a cytokine that enhances tissue repair after injury. This review compares the outcomes from use of EPO in the injured heart and kidney, two organs that are thought, traditionally, to have intrinsically-different repair mechanisms. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Ongoing work by us on EPO protection of ischemia-reperfusion-injured kidneys indicated, first, that EPO acutely enhanced kidney repair via anti-apoptotic, pro-regenerative mechanisms, and second, that EPO may promote chronic fibrosis in the long term. Work by others on the ischaemia-injured heart has also indicated that EPO promotes repair. Although myocardial infarcts are made up mostly of necrotic tissue, many publications state EPO is anti-apoptotic in the heart, as well as promoting healing via cell differentiation and stimulation of granulation tissue. In the case of the heart, promotion of fibrosis may be advantageous where an infarct has destroyed a zone of cardiomyocytes, but if EPO stimulates progressive fibrosis in the heart, this may promote cardiac failure. A major concern in relation to the use of EPO in a cytoprotective role is its stimulation of long-term inflammation and fibrosis. EPO usage for cytoprotection is undoubtedly advantageous, but it may need to be offset with an anti-inflammatory agent in some organs, like kidney and heart, where progression to chronic fibrosis after acute injury is often recorded.

A human pericardium biopolymeric scaffold for autologous heart valve tissue engineering: cellular and extracellular matrix structure and biomechanical properties in comparison with a normal aortic heart valve.

Science.gov (United States)

Straka, Frantisek; Schornik, David; Masin, Jaroslav; Filova, Elena; Mirejovsky, Tomas; Burdikova, Zuzana; Svindrych, Zdenek; Chlup, Hynek; Horny, Lukas; Daniel, Matej; Machac, Jiri; Skibová, Jelena; Pirk, Jan; Bacakova, Lucie

2018-04-01

The objective of our study was to compare the cellular and extracellular matrix (ECM) structure and the biomechanical properties of human pericardium (HP) with the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV samples (from 5 patients) were harvested during heart surgery. The main cells in HP were pericardial interstitial cells, which are fibroblast-like cells of mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The ECM of HP had a statistically significantly (p structures of the two tissues, the dense part of fibrous HP (49 ± 2%) and the lamina fibrosa of NAV (47 ± 4%), was similar. In both tissues, the secant elastic modulus (Es) was significantly lower in the transversal direction (p structure and has the biomechanical properties required for a tissue from which an autologous heart valve replacement may be constructed.

Heavy metals burden in Kidney and heart tissues of Scarus ...

African Journals Online (AJOL)

Levels of selected heavy metals (Pb, Co, Cu, Ni, Zn, Mn and Cd) in the heart and kidney tissues of parrot fish, collected from the Arabian Gulf, Eastern Province of Saudi Arabia, were determined by wet-digestion based atomic absorption method. The results showed that accumulation pattern of analyzed metals in the kidney ...

The local expression of adult chicken heart myosins during development. II. Ventricular conducting tissue

NARCIS (Netherlands)

Sanders, E.; de Groot, I. J.; Geerts, W. J.; de Jong, F.; van Horssen, A. A.; Los, J. A.; Moorman, A. F.

1986-01-01

The development of the ventricular conducting tissue of the embryonic chicken heart has been studied using a previous finding that morphologically recognizable atrial conducting tissue coexpresses the atrial and the ventricular myosin isoforms. It is found that, by these criteria, at 9 days part of

Design and efficacy of a single-use bioreactor for heart valve tissue engineering.

Science.gov (United States)

Converse, Gabriel L; Buse, Eric E; Neill, Kari R; McFall, Christopher R; Lewis, Holley N; VeDepo, Mitchell C; Quinn, Rachael W; Hopkins, Richard A

2017-02-01

Heart valve tissue engineering offers the promise of improved treatments for congenital heart disorders; however, widespread clinical availability of a tissue engineered heart valve (TEHV) has been hindered by scientific and regulatory concerns, including the lack of a disposable, bioreactor system for nondestructive valve seeding and mechanical conditioning. Here we report the design for manufacture and the production of full scale, functional prototypes of such a system. To evaluate the efficacy of this bioreactor as a tool for seeding, ovine aortic valves were decellularized and subjected to seeding with human mesenchymal stem cells (hMSC). The effects of pulsatile conditioning using cyclic waveforms tuned to various negative and positive chamber pressures were evaluated, with respect to the seeding of cells on the decellularized leaflet and the infiltration of seeded cells into the interstitium of the leaflet. Infiltration of hMSCs into the aortic valve leaflet was observed following 72 h of conditioning under negative chamber pressure. Additional conditioning under positive pressure improved cellular infiltration, while retaining gene expression within the MSC-valve interstitial cell phenotype lineage. This protocol resulted in a subsurface pilot population of cells, not full tissue recellularization. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 249-259, 2017. © 2015 Wiley Periodicals, Inc.

Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

International Nuclear Information System (INIS)

Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal; Thomsen, Bo; Larsen, Knud; Hedegaard, Jakob; Bendixen, Christian; Madsen, Lone Bruhn

2013-01-01

.e. cerebellum versus heart for differential variation at the gene, isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the “electron transport chain” and neuronal differentiation, emphasizing that “tissue important” genes are regulated at several levels. Furthermore, our analysis shows that the “across tissue approach” has a promising potential when screening for possible explanations for variations, such as those observed at the gene expression levels

Novel strong tissue specific promoter for gene expression in human germ cells

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Kuzmin Denis

2010-08-01

Full Text Available Abstract Background Tissue specific promoters may be utilized for a variety of applications, including programmed gene expression in cell types, tissues and organs of interest, for developing different cell culture models or for use in gene therapy. We report a novel, tissue-specific promoter that was identified and engineered from the native upstream regulatory region of the human gene NDUFV1 containing an endogenous retroviral sequence. Results Among seven established human cell lines and five primary cultures, this modified NDUFV1 upstream sequence (mNUS was active only in human undifferentiated germ-derived cells (lines Tera-1 and EP2102, where it demonstrated high promoter activity (~twice greater than that of the SV40 early promoter, and comparable to the routinely used cytomegaloviral promoter. To investigate the potential applicability of the mNUS promoter for biotechnological needs, a construct carrying a recombinant cytosine deaminase (RCD suicide gene under the control of mNUS was tested in cell lines of different tissue origin. High cytotoxic effect of RCD with a cell-death rate ~60% was observed only in germ-derived cells (Tera-1, whereas no effect was seen in a somatic, kidney-derived control cell line (HEK293. In further experiments, we tested mNUS-driven expression of a hyperactive Sleeping Beauty transposase (SB100X. The mNUS-SB100X construct mediated stable transgene insertions exclusively in germ-derived cells, thereby providing further evidence of tissue-specificity of the mNUS promoter. Conclusions We conclude that mNUS may be used as an efficient promoter for tissue-specific gene expression in human germ-derived cells in many applications. Our data also suggest that the 91 bp-long sequence located exactly upstream NDUFV1 transcriptional start site plays a crucial role in the activity of this gene promoter in vitro in the majority of tested cell types (10/12, and an important role - in the rest two cell lines.

Neuro-adaptive control in beating heart surgery based on the viscoelastic tissue model

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Setareh Rezakhani

2014-04-01

Full Text Available In this paper, the problem of 3D heart motion in beating heart surgery is resolved by proposing a parallel force-motion controller. Motion controller is designed based on neuro-adaptive approach to compensate 3D heart motion and deal with uncertainity in dynamic parameters, while an implicit force control is implemented by considering a viscoelastic tissue model. Stability analysis is proved through Lypanov’s stability theory and Barballet’s lemma. Simulation results, for D2M2 robot, which is done in nominal case and viscoelastic parameter mismatches demonstrate the robust performance of the controller.

Tissue Specific Promoters in Colorectal Cancer

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A. R. Rama

2015-01-01

Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

Are brain and heart tissue prone to the development of thiamine deficiency?

NARCIS (Netherlands)

Klooster, Astrid; Larkin, James R.; Wiersema-Buist, Janneke; Gans, Reinold O. B.; Thornalley, Paul J.; Navis, Gerjan; van Goor, Harry; Leuvenink, Henri G. D.; Bakker, Stephan J. L.

Thiamine deficiency is a continuing problem leading to beriberi and Wernicke's encephalopathy. The symptoms of thiamine deficiency develop in the heart, brain and neuronal tissue. Yet, it is unclear how rapid thiamine deficiency develops and which organs are prone to development of thiamine

Modeling the Human Scarred Heart In Vitro : Toward New Tissue Engineered Models

NARCIS (Netherlands)

Deddens, Janine C.; Sadeghi, Amir Hossein; Hjortnaes, Jesper; van Laake, Linda W.; Buijsrogge, Marc; Doevendans, Pieter A.; Khademhosseini, Ali; Sluijter, Joost P G

2017-01-01

Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An

Fatty acids of polar lipids in heart tissue are good taxonomic markers ...

African Journals Online (AJOL)

The fatty acid profiles in total, neutral and polar lipids in the heart tissues of five freshwater fish species (Nile perch Lates niloticus, Nile tilapia Oreochromis niloticus, marbled lungfish Protopterus aethiopicus, Bagrus docmak and African catfish Clarias gariepinus) from Lakes Victoria and Kyoga were determined ...

Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study

DEFF Research Database (Denmark)

Mogelvang, Rasmus; Sogaard, Peter; Pedersen, Sune A

2009-01-01

AIMS: To test the hypothesis that echocardiographic tissue Doppler imaging (TDI) reveals reduced myocardial function in hypertension, diabetes, and ischaemic heart disease (IHD) in the general population. METHODS AND RESULTS: Within a large, community-based population study, cardiac function...... and diastolic cardiac function in hypertension [n = 345; LD 10.1 (+/-standard deviation, SD 2.0 mm), P diabetes [n = 65; LD 9.8 (+/-SD 2.2 mm), P ....001] compared with controls [n = 533; LD 11.4 (+/-SD 2.0 mm); E/e' 9.0 (x/SD 1.3)]. This pattern remained significant after adjusting for age, sex, body mass index, heart rate, and the results of conventional echocardiography. CONCLUSION: In the general population, persons with hypertension, diabetes, or IHD...

Epicardial adipose tissue volume estimation by postmortem computed tomography of eviscerated hearts

DEFF Research Database (Denmark)

Hindsø, Louise; Jakobsen, Lykke S; Jacobsen, Christina

2017-01-01

Epicardial adipose tissue (EAT) may play a role in the development of coronary artery disease. The purpose of this study was to evaluate a method based on postmortem computed tomography (PMCT) for the estimation of EAT volume. We PMCT-scanned the eviscerated hearts of 144 deceased individuals, wh...

Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

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RINI PUSPITANINGRUM

2010-09-01

Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxiatolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

Myoglobin Expression in Chelonia mydas Brain, Heart and Liver Tissues

Directory of Open Access Journals (Sweden)

RINI PUSPITANINGRUM

2010-09-01

Full Text Available An understanding of the underpinning physiology and biochemistry of animals is essential to properly understand the impact of anthropogenic changes and natural catastrophes upon the conservation of endangered species. An observation on the tissue location of the key respiratory protein, myoglobin, now opens up new opportunities for understanding how hypoxia tolerance impacts on diving lifestyle in turtles. The respiratory protein, myoglobin has functions other than oxygen binding which are involved in hypoxia tolerance, including metabolism of reactive oxygen species and of the vascular function by metabolism of nitric oxide. Our work aims to determine whether myoglobin expression in the green turtle exists in multiple non muscle tissues and to confirm the hypothesis that reptiles also have a distributed myoglobin expression which is linked to the hypoxia-tolerant trait. This initial work in turtle hatch Chelonia mydas confirms the presence of myoglobin transcriptin brain, heart and liver tissues. Furthermore, it will serve as a tool for completing the sequence and generating an in situ hybridization probe for verifying of cell location in expressing tissues.

Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement.

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Vereckei, András; Fazakas, Adám; Baló, Timea; Fekete, Béla; Molnár, Mária Judit; Karádi, István

2013-04-01

The authors report a case of rare chloroquine cardiotoxicity mimicking connective tissue disease heart involvement in a 56-year-old woman with mixed connective tissue disease (MCTD) manifested suddenly as third degree A-V block with QT(c) interval prolongation and short torsade de pointes runs ultimately degenerating into ventricular fibrillation. Immunological tests suggested an MCTD flare, implying that cardiac arrest had resulted from myocardial involvement by MCTD. However, QT(c) prolongation is not a characteristic of cardiomyopathy caused by connective tissue disease, unless anti-Ro/SSA positivity is present, but that was not the case. Therefore, looking for another cause of QT(c) prolongation the possibility of chloroquine cardiotoxicity emerged, which the patient had been receiving for almost two years in supramaximal doses. Biopsy of the deltoid muscle was performed, because in chloroquine toxicity, specific lesions are present both in the skeletal muscle and in the myocardium, and electron microscopy revealed the accumulation of cytoplasmic curvilinear bodies, which are specific to antimalarial-induced myocyte damage and are absent in all other muscle diseases, except neuronal ceroid lipofuscinosis. Thus, the diagnosis of chloroquine cardiotoxicity was established. It might be advisable to supplement the periodic ophthalmological examination, which is currently the only recommendation for patients on long-term chloroquine therapy, with ECG screening.

Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

International Nuclear Information System (INIS)

Claffey, K.P.; Herrera, V.L.; Brecher, P.; Ruiz-Opazo, N.

1987-01-01

A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a λ gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundant mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source

Cloning and tissue distribution of rat hear fatty acid binding protein mRNA: identical forms in heart and skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Claffey, K.P.; Herrera, V.L.; Brecher, P.; Ruiz-Opazo, N.

1987-12-01

A fatty acid binding protein (FABP) as been identified and characterized in rat heart, but the function and regulation of this protein are unclear. In this study the cDNA for rat heart FABP was cloned from a lambda gt11 library. Sequencing of the cDNA showed an open reading frame coding for a protein with 133 amino acids and a calculated size of 14,776 daltons. Several differences were found between the sequence determined from the cDNA and that reported previously by protein sequencing techniques. Northern blot analysis using rat heart FABP cDNA as a probe established the presence of an abundant mRNA in rat heart about 0.85 kilobases in length. This mRNA was detected, but was not abundant, in fetal heart tissue. Tissue distribution studies showed a similar mRNA species in red, but not white, skeletal muscle. In general, the mRNA tissue distribution was similar to that of the protein detected by Western immunoblot analysis, suggesting that heart FABP expression may be regulated at the transcriptional level. S1 nuclease mapping studies confirmed that the mRNA hybridized to rat heart FABP cDNA was identical in heart and red skeletal muscle throughout the entire open reading frame. The structural differences between heart FABP and other members of this multigene family may be related to the functional requirements of oxidative muscle for fatty acids as a fuel source.

Exercise and Cardiac Function by Tissue Doppler Imaging. The Copenhagen City Heart Study

DEFF Research Database (Denmark)

Joseph, Gowsini; Sogaard, Peter; Nielsen, Gitte

2016-01-01

diastolic (e') and late diastolic (a') velocities were measured by color TDI. Longitudinal displacement (LD) was calculated from the velocity curve during ejection. Statistical tests were performed by linear univariate and multivariable regression analyses, in relation to age groups (lt;50years, 50-65 years......Introduction: TDI (Tissue Doppler Imaging) is a sensitive marker of myocardial dysfunction and mortality in heart disease and in the general population. Regular physical activity is associated with risk reduction in coronary heart disease and mortality. There is a need for studies to clarify...

Exercise and Cardiac Function by Tissue Doppler Imaging. The Copenhagen City Heart Study

DEFF Research Database (Denmark)

Joseph, Gowsini; Sogaard, Peter; Nielsen, Gitte

diastolic (e') and late diastolic (a') velocities were measured by color TDI. Longitudinal displacement (LD) was calculated from the velocity curve during ejection. Statistical tests were performed by linear univariate and multivariable regression analyses, in relation to age groups (lt;50years, 50-65 years......Introduction: TDI (Tissue Doppler Imaging) is a sensitive marker of myocardial dysfunction and mortality in heart disease and in the general population. Regular physical activity is associated with risk reduction in coronary heart disease and mortality. There is a need for studies to clarify...

Relationship between promoter methylation & tissue expression of MGMT gene in ovarian cancer

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V Shilpa

2014-01-01

Full Text Available Background & objectives: Epigenetic alterations, in addition to multiple gene abnormalities, are involved in the genesis and progression of human cancers. Aberrant methylation of CpG islands within promoter regions is associated with transcriptional inactivation of various tumour suppressor genes. O 6 -methyguanine-DNA methyltransferase (MGMT is a DNA repair gene that removes mutagenic and cytotoxic adducts from the O 6 -position of guanine induced by alkylating agents. MGMT promoter hypermethylation and reduced expression has been found in some primary human carcinomas. We studied DNA methylation of CpG islands of the MGMT gene and its relation with MGMT protein expression in human epithelial ovarian carcinoma. Methods: A total of 88 epithelial ovarian cancer (EOC tissue samples, 14 low malignant potential (LMP tumours and 20 benign ovarian tissue samples were analysed for MGMT promoter methylation by nested methylation-specific polymerase chain reaction (MSP after bisulphite modification of DNA. A subset of 64 EOC samples, 10 LMP and benign tumours and five normal ovarian tissue samples were analysed for protein expression by immunohistochemistry. Results: The methylation frequencies of the MGMT gene promoter were found to be 29.5, 28.6 and 20 per cent for EOC samples, LMP tumours and benign cases, respectively. Positive protein expression was observed in 93.8 per cent of EOC and 100 per cent in LMP, benign tumours and normal ovarian tissue samples. Promoter hypermethylation with loss of protein expression was seen only in one case of EOC. Interpretation & conclusions: Our results suggest that MGMT promoter hypermethylation does not always reflect gene expression.

Peptidomic Analysis of Fetal Heart Tissue for Identification of Endogenous Peptides Involved in Tetralogy of Fallot.

Science.gov (United States)

Zhang, Jingjing; Liang, Dong; Cheng, Qing; Cao, Li; Wu, Yun; Wang, Yan; Han, Shuping; Yu, Zhangbin; Cui, Xianwei; Xu, Tianhui; Ma, Dingyuan; Hu, Ping; Xu, Zhengfeng

2017-06-01

Tetralogy of fallot (TOF) is one of the most prevalent types of congenital heart diseases. As a category of bioactive molecules, peptides have been proved to participate in various biological processes. However, the role of endogenous peptides in the pathogenesis of TOF has not been studied. In this study, we performed a comparative peptidomic profile in the fetal heart of TOF and the control group for the first time by liquid chromatography-tandem mass spectrometry. Our data demonstrated that a total of 201 peptides derived from 176 precursor proteins were differentially expressed in the heart tissues of TOF fetuses compared with normal controls, including 41 upregulated peptides and 160 downregulated peptides. After analyzing the characteristics of these differentially expressed peptides and their precursor proteins, we found that these peptides were potentially involved in different biological processes, especially cardiogenesis and congenital anomaly of the cardiovascular system. Interestingly, we detected several extracellular matrix-derived peptides involved in our differentially expressed peptidomic profile. In summary, our study constructed a comparative peptidomic profile from the heart tissues of TOF fetuses and normal controls, and it identified a series of peptides that could potentially participate in heart development and TOF formation. The emergence of our peptidomics study indicated a new perspective to explore the pathogenesis of abnormal heart morphology, especially TOF.

Promoting tissue regeneration by modulating the immune system.

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Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

[Obesity and heart].

Science.gov (United States)

Svačina, Štěpán

2014-12-01

Cardiovascular complications of obesity are traditionally considered an important complication of obesity. Obesity itself is probably not direct cause of atherosclerosis or coronary heart disease. This may occur indirectly in metabolic complications of obesity, especially diabetes and metabolic syndrome. However, thrombogenicity potential of obesity contributes to embolism and atherosclerosis development. In cardiology is well-known a phenomenon of obesity paradox when obese patients have better prognosis than thin. This is the case of heart failure and some other cardiovascular diseases. Recently, a new concept has emerged of myokines - hormones from muscle tissue that have extensive protective effects on organism and probably on heart. Whether heart is a source of myokines is uncertain. However, undoubted importance has epicardial and pericardial fatty tissue. The epicardial fatty tissue has mainly protective effects on myocardium. This fatty tissue may produce factors of inflammation affecting the myocardium. Relationship between amount of epicardial fatty tissue and coronary heart disease is rather pathogenic. Currently, it is certain that obesity brings more metabolic and cancer complications than cardiovascular and accurate contribution to pathogenic or protective character of fatty tissue in cardiology requires further research. Nevertheless, the conclusion is that adipose tissue of organism and around the heart may be in some circumstances beneficial.

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

Science.gov (United States)

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

DNA entropy reveals a significant difference in complexity between housekeeping and tissue specific gene promoters.

Science.gov (United States)

Thomas, David; Finan, Chris; Newport, Melanie J; Jones, Susan

2015-10-01

The complexity of DNA can be quantified using estimates of entropy. Variation in DNA complexity is expected between the promoters of genes with different transcriptional mechanisms; namely housekeeping (HK) and tissue specific (TS). The former are transcribed constitutively to maintain general cellular functions, and the latter are transcribed in restricted tissue and cells types for specific molecular events. It is known that promoter features in the human genome are related to tissue specificity, but this has been difficult to quantify on a genomic scale. If entropy effectively quantifies DNA complexity, calculating the entropies of HK and TS gene promoters as profiles may reveal significant differences. Entropy profiles were calculated for a total dataset of 12,003 human gene promoters and for 501 housekeeping (HK) and 587 tissue specific (TS) human gene promoters. The mean profiles show the TS promoters have a significantly lower entropy (pentropy distributions for the 3 datasets show that promoter entropies could be used to identify novel HK genes. Functional features comprise DNA sequence patterns that are non-random and hence they have lower entropies. The lower entropy of TS gene promoters can be explained by a higher density of positive and negative regulatory elements, required for genes with complex spatial and temporary expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

3D force control for robotic-assisted beating heart surgery based on viscoelastic tissue model.

Science.gov (United States)

Liu, Chao; Moreira, Pedro; Zemiti, Nabil; Poignet, Philippe

2011-01-01

Current cardiac surgery faces the challenging problem of heart beating motion even with the help of mechanical stabilizer which makes delicate operation on the heart surface difficult. Motion compensation methods for robotic-assisted beating heart surgery have been proposed recently in literature, but research on force control for such kind of surgery has hardly been reported. Moreover, the viscoelasticity property of the interaction between organ tissue and robotic instrument further complicates the force control design which is much easier in other applications by assuming the interaction model to be elastic (industry, stiff object manipulation, etc.). In this work, we present a three-dimensional force control method for robotic-assisted beating heart surgery taking into consideration of the viscoelastic interaction property. Performance studies based on our D2M2 robot and 3D heart beating motion information obtained through Da Vinci™ system are provided.

Characterizing nanoscale topography of the aortic heart valve basement membrane for tissue engineering heart valve scaffold design.

Science.gov (United States)

Brody, Sarah; Anilkumar, Thapasimuthu; Liliensiek, Sara; Last, Julie A; Murphy, Christopher J; Pandit, Abhay

2006-02-01

A fully effective prosthetic heart valve has not yet been developed. A successful tissue-engineered valve prosthetic must contain a scaffold that fully supports valve endothelial cell function. Recently, topographic features of scaffolds have been shown to influence the behavior of a variety of cell types and should be considered in rational scaffold design and fabrication. The basement membrane of the aortic valve endothelium provides important parameters for tissue engineering scaffold design. This study presents a quantitative characterization of the topographic features of the native aortic valve endothelial basement membrane; topographical features were measured, and quantitative data were generated using scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and light microscopy. Optimal conditions for basement membrane isolation were established. Histological, immunohistochemical, and TEM analyses following decellularization confirmed basement membrane integrity. SEM and AFM photomicrographs of isolated basement membrane were captured and quantitatively analyzed. The basement membrane of the aortic valve has a rich, felt-like, 3-D nanoscale topography, consisting of pores, fibers, and elevations. All features measured were in the sub-100 nm range. No statistical difference was found between the fibrosal and ventricular surfaces of the cusp. These data provide a rational starting point for the design of extracellular scaffolds with nanoscale topographic features that mimic those found in the native aortic heart valve basement membrane.

Enlarged Heart

Science.gov (United States)

... rheumatic fever, a heart defect, infections (infectious endocarditis), connective tissue disorders, certain medications or radiation treatments for cancer, your heart may enlarge. Disease of the heart ...

Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes.

Science.gov (United States)

Zimmermann, W H; Fink, C; Kralisch, D; Remmers, U; Weil, J; Eschenhagen, T

2000-04-05

A technique is presented that allows neonatal rat cardiac myocytes to form spontaneously and coherently beating 3-dimensional engineered heart tissue (EHT) in vitro, either as a plane biconcaval matrix anchored at both sides on Velcro-coated silicone tubes or as a ring. Contractile activity was monitored in standard organ baths or continuously in a CO(2) incubator for up to 18 days (=26 days after casting). Long-term measurements showed an increase in force between days 8 and 18 after casting and stable forces thereafter. At day 10, the twitch amplitude (TA) of electrically paced EHTs (average length x width x thickness, 11 x 6 x 0.4 mm) was 0.51 mN at length of maximal force development (L(max)) and a maximally effective calcium concentration. EHTs showed typical features of neonatal rat heart: a positive force-length and a negative force-frequency relation, high sensitivity to calcium (EC(50) 0.24 mM), modest positive inotropic (increase in TA by 46%) and pronounced positive lusitropic effect of isoprenaline (decrease in twitch duration by 21%). Both effects of isoprenaline were sensitive to the muscarinic receptor agonist carbachol in a pertussis toxin-sensitive manner. Adenovirus-mediated gene transfer of beta-galactosidase into EHTs reached 100% efficiency. In summary, EHTs retain many of the physiological characteristics of rat cardiac tissue and allow efficient gene transfer with subsequent force measurement. Copyright 2000 John Wiley & Sons, Inc.

Osteoponin Promoter Controlled by DNA Methylation: Aberrant Methylation in Cloned Porcine Genome

Directory of Open Access Journals (Sweden)

Chih-Jie Shen

2014-01-01

Full Text Available Cloned animals usually exhibited many defects in physical characteristics or aberrant epigenetic reprogramming, especially in some important organ development. Osteoponin (OPN is an extracellular-matrix protein involved in heart and bone development and diseases. In this study, we investigated the correlation between OPN mRNA and its promoter methylation changes by the 5-aza-dc treatment in fibroblast cell and promoter assay. Aberrant methylation of porcine OPN was frequently found in different tissues of somatic nuclear transferred cloning pigs, and bisulfite sequence data suggested that the OPN promoter region −2615 to −2239 nucleotides (nt may be a crucial regulation DNA element. In pig ear fibroblast cell culture study, the demethylation of OPN promoter was found in dose-dependent response of 5-aza-dc treatment and followed the OPN mRNA reexpression. In cloned pig study, discrepant expression pattern was identified in several cloned pig tissues, especially in brain, heart, and ear. Promoter assay data revealed that four methylated CpG sites presenting in the −2615 to −2239 nt region cause significant downregulation of OPN promoter activity. These data suggested that methylation in the OPN promoter plays a crucial role in the regulation of OPN expression that we found in cloned pigs genome.

Heart-specific expression of laminopathic mutations in transgenic zebrafish.

Science.gov (United States)

Verma, Ajay D; Parnaik, Veena K

2017-07-01

Lamins are key determinants of nuclear organization and function in the metazoan nucleus. Mutations in human lamin A cause a spectrum of genetic diseases that affect cardiac muscle and skeletal muscle as well as other tissues. A few laminopathies have been modeled using the mouse. As zebrafish is a well established model for the study of cardiac development and disease, we have investigated the effects of heart-specific lamin A mutations in transgenic zebrafish. We have developed transgenic lines of zebrafish expressing conserved lamin A mutations that cause cardiac dysfunction in humans. Expression of zlamin A mutations Q291P and M368K in the heart was driven by the zebrafish cardiac troponin T2 promoter. Homozygous mutant embryos displayed nuclear abnormalities in cardiomyocyte nuclei. Expression analysis showed the upregulation of genes involved in heart regeneration in transgenic mutant embryos and a cell proliferation marker was increased in adult heart tissue. At the physiological level, there was deviation of up to 20% from normal heart rate in transgenic embryos expressing mutant lamins. Adult homozygous zebrafish were fertile and did not show signs of early mortality. Our results suggest that transgenic zebrafish models of heart-specific laminopathies show cardiac regeneration and moderate deviations in heart rate during embryonic development. © 2017 International Federation for Cell Biology.

Engineered Heart Repair.

Science.gov (United States)

Fujita, B; Zimmermann, W-H

2017-08-01

There is a pressing need for the development of advanced heart failure therapeutics. Current state-of-the-art is protection from neurohumoral overstimulation, which fails to address the underlying cause of heart failure, namely loss of cardiomyocytes. Implantation of stem cell-derived cardiomyocytes via tissue-engineered myocardium is being advanced to realize the remuscularization of the failing heart. Here, we discuss pharmacological challenges pertaining to the clinical translation of tissue-engineered heart repair with a focus on engineered heart muscle (EHM). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Decreased mechanical properties of heart valve tissue constructs cultured in platelet lysate as compared to fetal bovine serum

NARCIS (Netherlands)

Geemen, van D.; Riem Vis, P.W.; Soekhradj - Soechit, R.S.; Sluijter, J.P.G.; Liefde - van Beest, de M.; Kluin, J.; Bouten, C.V.C.

2011-01-01

In autologous heart valve tissue engineering, there is an ongoing search for alternatives of fetal bovine serum (FBS). Human platelet-lysate (PL) might be a promising substitute. In the present article, we aimed to examine the tissue formation, functionality, and mechanical properties of engineered

Tissue-type-specific transcriptome analysis identifies developing xylem-specific promoters in poplar.

Science.gov (United States)

Ko, Jae-Heung; Kim, Hyun-Tae; Hwang, Ildoo; Han, Kyung-Hwan

2012-06-01

Plant biotechnology offers a means to create novel phenotypes. However, commercial application of biotechnology in crop improvement programmes is severely hindered by the lack of utility promoters (or freedom to operate the existing ones) that can drive gene expression in a tissue-specific or temporally controlled manner. Woody biomass is gaining popularity as a source of fermentable sugars for liquid fuel production. To improve the quantity and quality of woody biomass, developing xylem (DX)-specific modification of the feedstock is highly desirable. To develop utility promoters that can drive transgene expression in a DX-specific manner, we used the Affymetrix Poplar Genome Arrays to obtain tissue-type-specific transcriptomes from poplar stems. Subsequent bioinformatics analysis identified 37 transcripts that are specifically or strongly expressed in DX cells of poplar. After further confirmation of their DX-specific expression using semi-quantitative PCR, we selected four genes (DX5, DX8, DX11 and DX15) for in vivo confirmation of their tissue-specific expression in transgenic poplars. The promoter regions of the selected DX genes were isolated and fused to a β-glucuronidase (GUS)-reported gene in a binary vector. This construct was used to produce transgenic poplars via Agrobacterium-mediated transformation. The GUS expression patterns of the resulting transgenic plants showed that these promoters were active in the xylem cells at early seedling growth and had strongest expression in the developing xylem cells at later growth stages of poplar. We conclude that these DX promoters can be used as a utility promoter for DX-specific biomass engineering. © 2012 The Authors. Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Favorable Effects of the Detergent and Enzyme Extraction Method for Preparing Decellularized Bovine Pericardium Scaffold for Tissue Engineered Heart Valves

NARCIS (Netherlands)

Yang, Min; Chen, Chang-Zhi; Wang, Xue-Ning; Zhu, Ya-Bin; Gu, Y. John

2009-01-01

Bovine pericardium has been extensively applied as the biomaterial for artificial heart valves and may potentially be used as a scaffold for tissue-engineered heart valves after decellularization. Although various methods of decellularization are currently available, it is unknown which method is

Analysis of tissue-specific region in sericin 1 gene promoter of Bombyx mori

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Yan, Liu [College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027 (China); Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Lian, Yu [College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310027 (China); Zhejiang Province Key Laboratory of Preventive Veterinary Medicine, Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310029 (China); Xiuyang, Guo [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Tingqing, Guo [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shengpeng, Wang [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Changde, Lu [Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

2006-03-31

The gene encoding sericin 1 (Ser1) of silkworm (Bombyx mori) is specifically expressed in the middle silk gland cells. To identify element involved in this transcription-dependent spatial restriction, truncation of the 5' terminal from the sericin 1 (Ser1) promoter is studied in vivo. A 209 bp DNA sequence upstream of the transcriptional start site (-586 to -378) is found to be responsible for promoting tissue-specific transcription. Analysis of this 209 bp region by overlapping deletion studies showed that a 25 bp region (-500 to -476) suppresses the ectopic expression of the Ser1 promoter. An unknown factor abundant in fat body nuclear extracts is shown to bind to this 25 bp fragment. These results suggest that this 25 bp region and the unknown factor are necessary for determining the tissue-specificity of the Ser1 promoter.

Tissue Inhibitor of Matrix Metalloproteinase-1 Promotes Myocardial Fibrosis by Mediating CD63-Integrin β1 Interaction.

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Takawale, Abhijit; Zhang, Pu; Patel, Vaibhav B; Wang, Xiuhua; Oudit, Gavin; Kassiri, Zamaneh

2017-06-01

Myocardial fibrosis is excess accumulation of the extracellular matrix fibrillar collagens. Fibrosis is a key feature of various cardiomyopathies and compromises cardiac systolic and diastolic performance. TIMP1 (tissue inhibitor of metalloproteinase-1) is consistently upregulated in myocardial fibrosis and is used as a marker of fibrosis. However, it remains to be determined whether TIMP1 promotes tissue fibrosis by inhibiting extracellular matrix degradation by matrix metalloproteinases or via an matrix metalloproteinase-independent pathway. We examined the function of TIMP1 in myocardial fibrosis using Timp1 -deficient mice and 2 in vivo models of myocardial fibrosis (angiotensin II infusion and cardiac pressure overload), in vitro analysis of adult cardiac fibroblasts, and fibrotic myocardium from patients with dilated cardiomyopathy (DCM). Timp1 deficiency significantly reduced myocardial fibrosis in both in vivo models of cardiomyopathy. We identified a novel mechanism for TIMP1 action whereby, independent from its matrix metalloproteinase-inhibitory function, it mediates an association between CD63 (cell surface receptor for TIMP1) and integrin β1 on cardiac fibroblasts, initiates activation and nuclear translocation of Smad2/3 and β-catenin, leading to de novo collagen synthesis. This mechanism was consistently observed in vivo, in cultured cardiac fibroblasts, and in human fibrotic myocardium. In addition, after long-term pressure overload, Timp1 deficiency persistently reduced myocardial fibrosis and ameliorated diastolic dysfunction. This study defines a novel matrix metalloproteinase-independent function of TIMP1 in promoting myocardial fibrosis. As such targeting TIMP1 could prove to be a valuable approach in developing antifibrosis therapies. © 2017 American Heart Association, Inc.

Cell Death and Heart Failure in Obesity: Role of Uncoupling Proteins

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Angélica Ruiz-Ramírez

2016-01-01

Full Text Available Metabolic diseases such as obesity, metabolic syndrome, and type II diabetes are often characterized by increased reactive oxygen species (ROS generation in mitochondrial respiratory complexes, associated with fat accumulation in cardiomyocytes, skeletal muscle, and hepatocytes. Several rodents studies showed that lipid accumulation in cardiac myocytes produces lipotoxicity that causes apoptosis and leads to heart failure, a dynamic pathological process. Meanwhile, several tissues including cardiac tissue develop an adaptive mechanism against oxidative stress and lipotoxicity by overexpressing uncoupling proteins (UCPs, specific mitochondrial membrane proteins. In heart from rodent and human with obesity, UCP2 and UCP3 may protect cardiomyocytes from death and from a state progressing to heart failure by downregulating programmed cell death. UCP activation may affect cytochrome c and proapoptotic protein release from mitochondria by reducing ROS generation and apoptotic cell death. Therefore the aim of this review is to discuss recent findings regarding the role that UCPs play in cardiomyocyte survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote heart protection.

Coping Styles Mediate the Relationship Between Self-esteem, Health Locus of Control, and Health-Promoting Behavior in Chinese Patients With Coronary Heart Disease.

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Zou, Huijing; Tian, Qian; Chen, Yuxia; Cheng, Cheng; Fan, Xiuzhen

Health-promoting behavior plays an important role in reducing the burden of coronary heart disease. Self-esteem and health locus of control may contribute to health-promoting behavior, and coping styles may mediate these associations. The aims of our study were to examine whether self-esteem and health locus of control are associated with health-promoting behavior and examine the possible mediating effect of coping styles in patients with coronary heart disease. Health-promoting behavior, self-esteem, health locus of control, and coping styles were assessed in 272 hospitalized patients (60 ± 12 years, 61% male) with coronary heart disease. Hierarchical regression analysis was conducted to analyze the relationships between health-promoting behavior and other variables. Mediation effect was examined according to the methods of Baron and Kenny. The mean score for health-promoting behavior was 2.57 ± 0.51; 38.2% of patients (n = 104) scored lower than 2.5. Self-esteem (β = .139, P locus of control and health-promoting behavior. Confrontation plays a mediating role in the association among self-esteem, internal health locus of control, and health-promoting behavior. Strategies should be undertaken to encourage the use of confrontation coping style, which will facilitate health-promoting behavior.

Importance of Pulmonary Vein Preferential Fibrosis for Atrial Fibrillation Promotion in Hypertensive Rat Hearts.

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Iwasaki, Yu-Ki; Yamashita, Takeshi; Sekiguchi, Akiko; Hayami, Noriyuki; Shimizu, Wataru

2016-06-01

Hypertension is one of the independent risk factors for atrial fibrillation (AF). Pulmonary veins (PVs) play an important role as the substrate for AF and triggers of AF. The purpose of this study was to determine the structural remodelling of the PVs and its effect on promoting AF in hypertensive (HT) rat hearts. Eighteen-week-old Dahl salt-sensitive HT rats and their controls were used for histological and immunohistological analyses, and electrophysiological studies were performed in Langendorff perfused hearts. Masson-trichrome staining revealed that hypertension significantly increased the fibrosis in the PVs, particularly in subendocardial and perivascular areas, compared with that in control rats, however, at this early stage of hypertension, left atrial fibrosis was not prominent. In the HT rat hearts with PVs, electrical stimulation significantly increased the number of repetitive atrial firing and atrial tachycardia inducibility, which significantly diminished after the excision of the PVs. An immunofluorescent analysis revealed that HT rats had PV specific endocardial smooth muscle actin (αSMA)-positive cells with remarkable proliferation of platelet-derived growth factor (PDGF)-C and vascular endothelial growth factor (VEGF), which was lacking in the left atrial structures of the control and the HT rats. Pretreatment with imatinib, a PDGF receptor activity blocker, in HT rats reduced the αSMA-positive cell proliferation and fibrosis in the PVs and also induced a significant reduction in VEGF expression. Also, the drug pretreatment effectively prevented repetitive atrial firing promotion without affecting the blood pressure. PV preferential fibrosis might play an important role in the arrhythmogenic substrate of AF in HT rat hearts. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Post-mortem detection of gasoline residues in lung tissue and heart blood of fire victims.

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Pahor, Kevin; Olson, Greg; Forbes, Shari L

2013-09-01

The purpose of this study was to determine whether gasoline residues could be detected post-mortem in lung tissue and heart blood of fire victims. The lungs and heart blood were investigated to determine whether they were suitable samples for collection and could be collected without contamination during an autopsy. Three sets of test subjects (pig carcasses) were investigated under two different fire scenarios. Test subjects 1 were anaesthetized following animal ethics approval, inhaled gasoline vapours for a short period and then euthanized. The carcasses were clothed and placed in a house where additional gasoline was poured onto the carcass post-mortem in one fire, but not in the other. Test subjects 2 did not inhale gasoline, were clothed and placed in the house and had gasoline poured onto them in both fires. Test subjects 3 were clothed but had no exposure to gasoline either ante- or post-mortem. Following controlled burns and suppression with water, the carcasses were collected, and their lungs and heart blood were excised at a necropsy. The headspace from the samples was analysed using thermal desorption-gas chromatography-mass spectroscopy. Gasoline was identified in the lungs and heart blood from the subjects that were exposed to gasoline vapours prior to death (test subjects 1). All other samples were negative for gasoline residues. These results suggest that it is useful to analyse for volatile ignitable liquids in lung tissue and blood as it may help to determine whether a victim was alive and inhaling gases at the time of a fire.

Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

International Nuclear Information System (INIS)

Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

2013-01-01

Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

Measurement of capillary permeability in canine heart determined by the tissue injection, residue detection method

DEFF Research Database (Denmark)

Svendsen, Jesper Hastrup; Paaske, W P; Haunsø, S

1991-01-01

(apparent) interstitial volume of distribution, tev is the mean transit time of the indicator, and klo is the recorded fractional initial washout rate constant. In experiments on open chest dog hearts we examined capillary permeability for 51Cr-EDTA and 99mTc-DTPA with the tissue injection, residue...

Soapwort extract supplementation alters antioxidant status of serum, liver and heart tissues in growing Japanese quails reared under chronic intermittent cold stress

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Bestami Dalkilic

2017-01-01

Full Text Available Antioxidant effect of dietary soapwort extract supplementation was studied in growing Japanese quails suffering from chronic intermittent cold stress. For this purpose, a total of ninety 15-d-old quails were divided into three groups with three replicates. Chronic intermittent cold stress was applied every night between 22.00 to 06.00 h; starting at 14 °C for the first week, and gradually weekly lowered to 8 °C. Three groups were fed with corn-soy based standard diets supplemented with 0, 50, and 100 ppm soapwort extract for four weeks. At the end of the study, three males and three females were slaughtered to determine total antioxidant and oxidant status of serum, malondialdehyde, glutathione, glutathione peroxidase activity, superoxide dismutase of liver and heart tissues. Although the dietary soapwort extract had no effect on serum total antioxidant capacity, it significantly lowered the total oxidant status of serum in cold stressed quails. Glutathione and superoxide dismutase enzyme activity of liver and heart tissues were similar among groups. While the dietary soapwort extract had no effect on glutathione peroxidase activity of the heart tissue, it significantly increased glutathione peroxidase activity in the liver tissue. In relation to the control group, malondialdehyde concentrations in the liver and heart tissues were significantly lower in soapwort extract groups. These data suggest that dietary soapwort extract could alleviate the detrimental effects of oxidative stress in growing Japanese quails exposed to cold stress.

Label-free protein profiling of formalin-fixed paraffin-embedded (FFPE) heart tissue reveals immediate mitochondrial impairment after ionising radiation.

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Azimzadeh, Omid; Scherthan, Harry; Yentrapalli, Ramesh; Barjaktarovic, Zarko; Ueffing, Marius; Conrad, Marcus; Neff, Frauke; Calzada-Wack, Julia; Aubele, Michaela; Buske, Christian; Atkinson, Michael J; Hauck, Stefanie M; Tapio, Soile

2012-04-18

Qualitative proteome profiling of formalin-fixed, paraffin-embedded (FFPE) tissue is advancing the field of clinical proteomics. However, quantitative proteome analysis of FFPE tissue is hampered by the lack of an efficient labelling method. The usage of conventional protein labelling on FFPE tissue has turned out to be inefficient. Classical labelling targets lysine residues that are blocked by the formalin treatment. The aim of this study was to establish a quantitative proteomics analysis of FFPE tissue by combining the label-free approach with optimised protein extraction and separation conditions. As a model system we used FFPE heart tissue of control and exposed C57BL/6 mice after total body irradiation using a gamma ray dose of 3 gray. We identified 32 deregulated proteins (p≤0.05) in irradiated hearts 24h after the exposure. The proteomics data were further evaluated and validated by bioinformatics and immunoblotting investigation. In good agreement with our previous results using fresh-frozen tissue, the analysis indicated radiation-induced alterations in three main biological pathways: respiratory chain, lipid metabolism and pyruvate metabolism. The label-free approach enables the quantitative measurement of radiation-induced alterations in FFPE tissue and facilitates retrospective biomarker identification using clinical archives. Copyright © 2012 Elsevier B.V. All rights reserved.

Eating Well While Dining Out: Collaborating with Local Restaurants to Promote Heart Healthy Menu Items

Science.gov (United States)

Thayer, Linden M.; Pimentel, Daniela C.; Smith, Janice C.; Garcia, Beverly A.; Sylvester, Laura Lee; Kelly, Tammy; Johnston, Larry F.; Ammerman, Alice S.; Keyserling, Thomas C.

2017-01-01

Background: Because Americans commonly consume restaurant foods with poor dietary quality, effective interventions are needed to improve food choices at restaurants. Purpose: The purpose of this study was to design and evaluate a restaurant-based intervention to help customers select and restaurants promote heart healthy menu items with healthful…

Brown adipose tissue: The heat is on the heart.

Science.gov (United States)

Thoonen, Robrecht; Hindle, Allyson G; Scherrer-Crosbie, Marielle

2016-06-01

The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. Copyright © 2016 the American Physiological Society.

Stem Cells for Cardiac Regeneration by Cell Therapy and Myocardial Tissue Engineering

Science.gov (United States)

Wu, Jun; Zeng, Faquan; Weisel, Richard D.; Li, Ren-Ke

Congestive heart failure, which often occurs progressively following a myocardial infarction, is characterized by impaired myocardial perfusion, ventricular dilatation, and cardiac dysfunction. Novel treatments are required to reverse these effects - especially in older patients whose endogenous regenerative responses to currently available therapies are limited by age. This review explores the current state of research for two related approaches to cardiac regeneration: cell therapy and tissue engineering. First, to evaluate cell therapy, we review the effectiveness of various cell types for their ability to limit ventricular dilatation and promote functional recovery following implantation into a damaged heart. Next, to assess tissue engineering, we discuss the characteristics of several biomaterials for their potential to physically support the infarcted myocardium and promote implanted cell survival following cardiac injury. Finally, looking ahead, we present recent findings suggesting that hybrid constructs combining a biomaterial with stem and supporting cells may be the most effective approaches to cardiac regeneration.

Are adipose-derived stem cells cultivated in human platelet lysate suitable for heart valve tissue engineering?

NARCIS (Netherlands)

Frese, L.; Sasse, T.; Sanders, B.; Baaijens, F.P.T.; Beer, G.M.; Hoerstrup, S.P.

2017-01-01

Tissue-engineered heart valves represent a promising strategy for the growing need for valve replacements in cardiovascular medicine. Recent studies have shown that adipose-derived stem cells (ADSC) are a viable cell source, as they are readily available in both the young and the elderly, show

An Ineffective Differential Diagnosis of Infective Endocarditis and Rheumatic Heart Disease after Streptococcal Skin and Soft Tissue Infection.

Science.gov (United States)

Suzuki, Tetsuya; Mawatari, Momoko; Iizuka, Toshihiko; Amano, Tatsuya; Kutsuna, Satoshi; Fujiya, Yoshihiro; Takeshita, Nozomi; Hayakawa, Kayoko; Ohmagari, Norio

2017-09-01

We herein report the case of a 68-year-old woman with a skin and soft tissue infection at her extremities. The blood culture results were positive for Streptococcus pyogenes, and we started treatment using ampicillin and clindamycin, although subsequent auscultation revealed a new-onset heart murmur. We therefore suspected rheumatic heart disease and infective endocarditis. The case met both the Jones criteria and the modified Duke criteria. Transesophageal echocardiography revealed vegetation on the aortic valve, although the pathological findings were also compatible with both rheumatic heart disease and infective endocarditis. The present findings suggest that these two diseases can coexist in some cases.

Heart Disease

Science.gov (United States)

... it may be caused by diseases, such as connective tissue disorders, excessive iron buildup in your body (hemochromatosis), the buildup of abnormal proteins (amyloidosis) or by some cancer treatments. Causes of heart infection A heart infection, ...

Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.

Directory of Open Access Journals (Sweden)

Matthew A Schechter

Full Text Available The molecular differences between ischemic (IF and non-ischemic (NIF heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins and 823 phosphopeptides (corresponding to 400 proteins from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05 when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.

Nicotine affects hydrogen sulfide concentrations in mouse kidney and heart but not in brain and liver tissues.

Science.gov (United States)

Wiliński, Jerzy; Wiliński, Bogdan; Somogyi, Eugeniusz; Piotrowska, Joanna; Kameczura, Tomasz; Zygmunt, Małgorzata

2017-01-01

Nicotine, a potent parasympathomimetic alkaloid with stimulant effects, is contributing to addictive properties of tobacco smoking and is though used in the smoking cessation therapy. Hydrogen sulfide (H2S) is involved in physiology and pathophysiology of various systems in mammals. The interactions between nicotine and H2S are not fully recognized. The aim of the study is to assess the influence of nicotine on the H2S tissue concentrations in different mouse organs. Adult CBA male mice were administered intraperitoneally 1.5 mg/kg b.w. per day of nicotine (group D1, n = 10) or 3 mg/ kg b.w. per day of nicotine (group D2, n = 10). The control group (n = 10) received physiological saline. The measurements of the free and acid-labile H2S tissue concentrations were performed with the Siegel spectrophotometric modi ed method. ere was a significant increase in H2S concentrations in both nicotine doses groups in the kidney (D1 by 54.2%, D2 by 40.0%). In the heart the higher nicotine dose caused a marked decrease in H2S tissue level (by 65.4%), while the lower dose did not affect H2S content. Nicotine administration had no effect on H2S concentrations in the brain and liver. In conclusion, nicotine affects H2S tissue concentrations in kidney and heart but not in the liver and brain tissues.

Alternative Promoter Usage in Healthy and Inflamed Tissue

DEFF Research Database (Denmark)

Lilje, Berit

and cell-lines covering the entire human body. This provides a unique dataset to study gene expression, with promoter level precision. Here we use this large collection of data to study alternative transcription start site usage throughout the human body. We find that many alternative transcription start...... with tumour necrosis factor alpha, and on tissue from mice subjected to carbon nanotubes. Both systems show a strong response, with especially alternative transcription start sites being differentially regulated. Taken together this shows that alternative transcription start sites add an important layer...

Systemic Lupus Erythematosus and Systemic Autoimmune Connective Tissue Disorders behind Recurrent Diastolic Heart Failure

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Luis Miguel Blasco Mata

2012-01-01

Full Text Available Diastolic heart failure (DHF remains unexplained in some patients with recurrent admissions after full investigation. A study was directed for screening SLE and systemic autoimmune connective tissue disorders in recurrent unexplained DHF patients admitted at a short-stay and intermediate care unit. It was found that systemic autoimmune conditions explained 11% from all of cases. Therapy also prevented new readmissions. Autoimmunity should be investigated in DHF.

Azacytidine and miR156 promote rooting in adult but not in juvenile Arabidopsis tissues.

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Massoumi, Mehdi; Krens, Frans A; Visser, Richard G F; De Klerk, Geert-Jan M

2017-01-01

Poor adventitious root (AR) formation is a major obstacle in micropropagation and conventional vegetative propagation of many crops. It is affected by many endogenous and exogenous factors. With respect to endogenous factors, the phase change from juvenile to adult has a major influence on AR formation and rooting is usually much reduced or even fully inhibited in adult tissues. It has been reported that the phase change is characterized by an increase in DNA-methylation and a decrease in the expression of microRNA156 (miR156). In this paper, we examined the effect of azacytidine (AzaC) and miR156 on AR formation in adult and juvenile Arabidopsis tissues. To identify the ontogenetic state researchers have used flowering or leaf morphology. We have used the rootability which allows - in contrast with both other characteristics- to examine the ontogenetic state at the cellular level. Overexpression of miR156 promoted only the rooting of adult tissues indicating that the phase change-associated loss in tissues' competence to develop ARs is also under the control of miR156. Azacytidine inhibits DNA methylation during DNA replication. Azacytidine treatment also promoted AR formation in nonjuvenile tissues but had no or little effect in juvenile tissues. Its addition during seedling growth (by which all tissues become hypomethylated) or during the rooting treatment (by which only those cells become hypomethylated that are generated after taking the explant) are both effective in the promotion of rooting. An AzaC treatment may be useful in tissue culture for crops that are recalcitrant to root. Copyright © 2016 Elsevier GmbH. All rights reserved.

Tissue-specific interactions between nuclear proteins and the aminopeptidase N promoter

DEFF Research Database (Denmark)

Kärnström, U; Sjöström, H; Norén, O

1991-01-01

Aminopeptidase N/CD13 is a metallopeptidase found in many tissues. Aminopeptidase N activity is high in the small intestinal mucosa, moderate in the liver, and low in the spleen. Using DNase I footprinting and electrophoretic mobility shift assays with nuclear extracts from these tissues, three cis...... elements (DF, LF-B1, UF) were identified in the aminopeptidase N promoter. The DF region (-53 to -30) interacts with the ubiquitously expressed transcription factor Sp1. The LF-B1 region (-85 to -58) interacts with the liver transcription factor LF-B1 (HNF-1) which was detected as well in nuclei from small...... intestinal mucosa. The UF region (-112 to -90) interacts with nuclear factors which seem to be expressed differentially in the liver and the small intestine. Transfection of promoter deletions into HepG2 cells showed that the LF-B1 region is necessary for high expression of the aminopeptidase N gene in liver...

Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

Science.gov (United States)

Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

2012-05-01

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

Adding the 'heart' to hanging drop networks for microphysiological multi-tissue experiments.

Science.gov (United States)

Rismani Yazdi, Saeed; Shadmani, Amir; Bürgel, Sebastian C; Misun, Patrick M; Hierlemann, Andreas; Frey, Olivier

2015-11-07

Microfluidic hanging-drop networks enable culturing and analysis of 3D microtissue spheroids derived from different cell types under controlled perfusion and investigating inter-tissue communication in multi-tissue formats. In this paper we introduce a compact on-chip pumping approach for flow control in hanging-drop networks. The pump includes one pneumatic chamber located directly above one of the hanging drops and uses the surface tension at the liquid-air-interface for flow actuation. Control of the pneumatic protocol provides a wide range of unidirectional pulsatile and continuous flow profiles. With the proposed concept several independent hanging-drop networks can be operated in parallel with only one single pneumatic actuation line at high fidelity. Closed-loop medium circulation between different organ models for multi-tissue formats and multiple simultaneous assays in parallel are possible. Finally, we implemented a real-time feedback control-loop of the pump actuation based on the beating of a human iPS-derived cardiac microtissue cultured in the same system. This configuration allows for simulating physiological effects on the heart and their impact on flow circulation between the organ models on chip.

Substantial species differences in relation to formation and degradation of N-acyl-ethanolamine phospholipids in heart tissue

DEFF Research Database (Denmark)

Moesgaard, B.; Petersen, G.; Hansen, Harald S.

2002-01-01

beneficial effects on the heart, but in the literature there are indications of species differences in the activity of these enzymes. We have examined heart microsomes from rats, mice, guinea pigs, rabbits, frogs, cows, dogs, cats, mini pigs and human beings for activities of these two enzymes. N......-Acyl-transferase activity was very high in dogs and cats (>13 pmol/min/mg protein) whereas it was very low to barely detectable in the other species (45 pmol/min/mg protein) whereas it was 9 pmol/min/mg protein in frogs and below that in the other species. The ratio of activity between the two enzymes varied from 0.......002 to 15 in the investigated species. The activity of the two enzymes in rat hearts as opposed to rat brain did not change during development. These results indicate that there may be substantial species differences in the generation of anandamide and other NAEs as well as NAPEs in heart tissues....

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

International Nuclear Information System (INIS)

Asting, Annika Gustafsson; Carén, Helena; Andersson, Marianne; Lönnroth, Christina; Lagerstedt, Kristina; Lundholm, Kent

2011-01-01

Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4) showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3) were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue

COX-2 gene expression in colon cancer tissue related to regulating factors and promoter methylation status

Directory of Open Access Journals (Sweden)

Lagerstedt Kristina

2011-06-01

Full Text Available Abstract Background Increased cyclooxygenase activity promotes progression of colorectal cancer, but the mechanisms behind COX-2 induction remain elusive. This study was therefore aimed to define external cell signaling and transcription factors relating to high COX-2 expression in colon cancer tissue. Method Tumor and normal colon tissue were collected at primary curative operation in 48 unselected patients. COX-2 expression in tumor and normal colon tissue was quantified including microarray analyses on tumor mRNA accounting for high and low tumor COX-2 expression. Cross hybridization was performed between tumor and normal colon tissue. Methylation status of up-stream COX-2 promoter region was evaluated. Results Tumors with high COX-2 expression displayed large differences in gene expression compared to normal colon. Numerous genes with altered expression appeared in tumors of high COX-2 expression compared to tumors of low COX-2. COX-2 expression in normal colon was increased in patients with tumors of high COX-2 compared to normal colon from patients with tumors of low COX-2. IL1β, IL6 and iNOS transcripts were up-regulated among external cell signaling factors; nine transcription factors (ATF3, C/EBP, c-Fos, Fos-B, JDP2, JunB, c-Maf, NF-κB, TCF4 showed increased expression and 5 (AP-2, CBP, Elk-1, p53, PEA3 were decreased in tumors with high COX-2. The promoter region of COX-2 gene did not show consistent methylation in tumor or normal colon tissue. Conclusions Transcription and external cell signaling factors are altered as covariates to COX-2 expression in colon cancer tissue, but DNA methylation of the COX-2 promoter region was not a significant factor behind COX-2 expression in tumor and normal colon tissue.

Women-Centered and Culturally Responsive Heart Health Promotion Among Indigenous Women in Canada.

Science.gov (United States)

Ziabakhsh, Shabnam; Pederson, Ann; Prodan-Bhalla, Natasha; Middagh, Diane; Jinkerson-Brass, Sharon

2016-11-01

Most women in Canada confront a combination of bio-psychosocial factors that put them at risk for cardiovascular disease. The challenge for health planners is to address these factors while contextualizing interventions that meet the specific needs of particular social and cultural groupings. The article will discuss a women-centered, group-based heart health pilot initiative designed to engage with indigenous approaches to healing. The nurse practitioners co-led the group with a representative from the indigenous community to balance women-centered practices with more traditional and culturally appropriate ones. In particular, indigenous processes, such as a Talking Circle, combined with indigenous knowledge/content were integrated into the pilot program. The project was evaluated to investigate its outcomes (how the intervention impacted the participants) and processes (how participants perceived the intervention). Evaluation involved analysis of the Talking Circle's content, a focus group, field observations, and self-completed surveys. Most women made changes regarding their diet, some began physical activities, and others focused on better managing their emotional health. Women viewed the group as successful because it embraced both women-centered and culturally appropriate health promotion practices. The intervention created a culturally safe space for learning and transformation. The findings confirm the need for employing culturally relevant, gender-specific approaches to heart health promotion that are situated in and responsive to community needs. © 2016 Society for Public Health Education.

Plasma and tissue oxidative stress index in patients with rheumatic and degenerative heart valve disease.

Science.gov (United States)

Rabus, Murat; Demirbağ, Recep; Sezen, Yusuf; Konukoğlu, Oğuz; Yildiz, Ali; Erel, Ozcan; Zeybek, Rahmi; Yakut, Cevat

2008-12-01

We investigated whether patients with rheumatic and degenerative heart valve disease (HVD) differed with regard to plasma and tissue oxidative stress index (OSI). The study included 56 patients who underwent valve replacement due to rheumatic (n=32; 15 males; mean age 47+/-10 years) and degenerative (n=24; 13 males; mean age 55+/-12 years) HVD. Plasma and tissue total oxidative status (TOS) and total antioxidative capacity (TAC) levels were measured and OSI was calculated. Patients with degenerative HVD had significantly higher age, increased interventricular septum thickness, and higher frequency of aortic stenosis, whereas the incidence of mitral stenosis was higher in patients with rheumatic HVD (p0.05). Tissue TAC was significantly lower in patients with rheumatic HVD (p=0.027), whereas tissue TOS and OSI were similar between the two HVD groups (p>0.05). In bivariate analysis, plasma OSI did not show any correlation with clinical, laboratory, and echocardiographic variables (p>0.05). Our data show that plasma and tissue OSI levels are similar in patients with rheumatic and degenerative HVD.

Regeneration of soft tissues is promoted by MMP1 treatment after digit amputation in mice.

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Xiaodong Mu

Full Text Available The ratio of matrix metalloproteinases (MMPs to the tissue inhibitors of metalloproteinases (TIMPs in wounded tissues strictly control the protease activity of MMPs, and therefore regulate the progress of wound closure, tissue regeneration and scar formation. Some amphibians (i.e. axolotl/newt demonstrate complete regeneration of missing or wounded digits and even limbs; MMPs play a critical role during amphibian regeneration. Conversely, mammalian wound healing re-establishes tissue integrity, but at the expense of scar tissue formation. The differences between amphibian regeneration and mammalian wound healing can be attributed to the greater ratio of MMPs to TIMPs in amphibian tissue. Previous studies have demonstrated the ability of MMP1 to effectively promote skeletal muscle regeneration by favoring extracellular matrix (ECM remodeling to enhance cell proliferation and migration. In this study, MMP1 was administered to the digits amputated at the mid-second phalanx of adult mice to observe its effect on digit regeneration. Results indicated that the regeneration of soft tissue and the rate of wound closure were significantly improved by MMP1 administration, but the elongation of the skeletal tissue was insignificantly affected. During digit regeneration, more mutipotent progenitor cells, capillary vasculature and neuromuscular-related tissues were observed in MMP1 treated tissues; moreover, there was less fibrotic tissue formed in treated digits. In summary, MMP1 was found to be effective in promoting wound healing in amputated digits of adult mice.

Detection of neuronal tissue in meat using tissue specific DNA modifications

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Harris N.

2004-01-01

Full Text Available A method has been developed to differentiate between non-muscle tissues such as liver, kidney and heart and that of muscle in meat samples using tissue specific DNA detection. Only muscle tissue is considered meat from the point of view of labelling (Food Labelling [Amendment] (England Regulations 2003 and Quantitative Ingredient Declaration (QUID, and also certain parts of the carcass are prohibited to be used in raw meat products (Meat Products [England] Regulations 2003. Included in the prohibited offal are brain and spinal cord. The described methodology has therefore been developed primarily to enforce labelling rules but also to contribute to the enforcement of BSE legislation on the detection of Central Nervous System (CNS tissue. The latter requires the removal of Specified Risk Material (SRM, such as bovine and ovine brain and spinal cord, from the food chain. Current methodologies for detection of CNS tissue include histological examination, analysis of cholesterol content and immunodetection. These can potentially be time consuming, less applicable to processed samples and may not be readily adapted to high throughput sample analysis. The objective of this work was therefore to develop a DNAbased detection assay that exploits the sensitivity and specificity of PCR and is potentially applicable to more highly processed food samples. For neuronal tissue, the DNA target selected was the promoter for Glial Fibrillary Acidic Protein (GFAP, a gene whose expression is restricted to astroglial cells within CNS tissue. The promoter fragments from both cattle and sheep have been isolated and key differences in the methylation patterns of certain CpG dinucleotides in the sequences from bovine and sheep brain and spinal cord and the corresponding skeletal muscle identified. These have been used to design a PCR assay exploiting Methylation Specific PCR (MSP to specifically amplify the neuronal tissue derived sequence and therefore identify the

Expression and biochemical characteristics of two different aldosterone receptors in both healthy and dilated cardiomyopathy dog heart tissue.

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Reynoso Palomar, Alejandro R; Rodriguez Bravo, Moncerrat; Villa Mancera, Abel E; Mucha, Carlos J

2017-03-01

Recently, replicates of the aldosterone receptor expression have been done in healthy heart dog tissues through immunohistochemistry, showing an apparent heterogeneous distribution in the four chambers. Recent studies have also identified immediate effects of aldosterone, suggesting aldosterone also produces non-genomic effects caused by an unidentified receptor. In order to study the molecular and quantitative expression characteristics of aldosterone binding receptors in the canine heart, we conducted studies, using Western Blot, in the heart from both healthy animals and animals with dilated cardiomyopathy. The results show the presence and distribution of two aldosterone receptors; one of 110/120 kDa molecular weight, suggested as cytosolic/nuclear and the other of undetermined location with a 250 kDa molecular weight.

ChIP-seq Identification of Weakly Conserved Heart Enhancers

Energy Technology Data Exchange (ETDEWEB)

Blow, Matthew J.; McCulley, David J.; Li, Zirong; Zhang, Tao; Akiyama, Jennifer A.; Holt, Amy; Plajzer-Frick, Ingrid; Shoukry, Malak; Wright, Crystal; Chen, Feng; Afzal, Veena; Bristow, James; Ren, Bing; Black, Brian L.; Rubin, Edward M.; Visel, Axel; Pennacchio, Len A.

2010-07-01

Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme non-coding sequence conservation successfully predicts enhancers active in many tissues, but fails to identify substantial numbers of heart enhancers. Here we used ChIP-seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over three thousand candidate heart enhancers genome-wide. Compared to other tissues studied at this time-point, most candidate heart enhancers are less deeply conserved in vertebrate evolution. Nevertheless, the testing of 130 candidate regions in a transgenic mouse assay revealed that most of them reproducibly function as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary constraint of embryonic enhancers can vary depending on tissue type.

Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs.

Science.gov (United States)

Yu, Hong; Bao, En-Dong; Zhao, Ru-Qian; Lv, Qiong-Xia

2007-11-01

To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs. 24 pigs (mean weight, 20 +/- 1 kg). Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA. No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs. Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.

Trace Elements in the Conductive Tissue of Beef Heart Determined by Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Wester, P O

1965-08-15

By means of neutron activation analysis, samples of four beef hearts taken from the bundle of His and adjacent ventricular muscle, the AV node and adjacent atrial muscle are investigated with respect to the concentration of 23 trace elements. The bulk elements K, Na and P are also determined. A recently developed ion-exchange technique, combined with subsequent {gamma}-spectrometry, is used. The following trace elements are determined: Ag, As, Au, Ba, Br, .Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Rb, Sb, Sc, Se, Sm, W and Zn. In the conductive tissue compared to adjacent muscle tissue, calculations on a wet weight basis show a lower concentration of Cs, Cu, Fe, K, P, Rb and Zn in the former, and a higher concentration of Ag, Au, Br, Ca and Na. The mean differences ({mu}g/g wet tissue), as well as their degree of significance, between the bundle of His and adjacent tissue from the ventricular septum, between the AV node and adjacent atrial muscle, between the ventricular septum and the right atrium, and between the bundle of His and the AV node are given for the elements Cu, Fe, K, Na, P and Zn.

Trace Elements in the Conductive Tissue of Beef Heart Determined by Neutron Activation Analysis

International Nuclear Information System (INIS)

Wester, P.O.

1965-08-01

By means of neutron activation analysis, samples of four beef hearts taken from the bundle of His and adjacent ventricular muscle, the AV node and adjacent atrial muscle are investigated with respect to the concentration of 23 trace elements. The bulk elements K, Na and P are also determined. A recently developed ion-exchange technique, combined with subsequent γ-spectrometry, is used. The following trace elements are determined: Ag, As, Au, Ba, Br, .Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Rb, Sb, Sc, Se, Sm, W and Zn. In the conductive tissue compared to adjacent muscle tissue, calculations on a wet weight basis show a lower concentration of Cs, Cu, Fe, K, P, Rb and Zn in the former, and a higher concentration of Ag, Au, Br, Ca and Na. The mean differences (μg/g wet tissue), as well as their degree of significance, between the bundle of His and adjacent tissue from the ventricular septum, between the AV node and adjacent atrial muscle, between the ventricular septum and the right atrium, and between the bundle of His and the AV node are given for the elements Cu, Fe, K, Na, P and Zn

Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic mice.

Science.gov (United States)

Eren, M; Painter, C A; Gleaves, L A; Schoenhard, J A; Atkinson, J B; Brown, N J; Vaughan, D E

2003-11-01

Numerous studies have described regulatory factors and sequences that control transcriptional responses in vitro. However, there is a paucity of information on the qualitative and quantitative regulation of heterologous promoters using transgenic strategies. In order to investigate the physiological regulation of human plasminogen activator inhibitor type-1 (hPAI-1) expression in vivo compared to murine PAI-1 (mPAI-1) and to test the physiological relevance of regulatory mechanisms described in vitro, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the proximal -2.9 kb of the hPAI-1 promoter. Transgenic animals were treated with Ang II, TGF-beta1 and lipopolysaccharide (LPS) to compare the relative activation of the human and murine PAI-1 promoters. Ang II increased EGFP expression most effectively in brain, kidney and spleen, while mPAI-1 expression was quantitatively enhanced most prominently in heart and spleen. TGF-beta1 failed to induce activation of the hPAI-1 promoter but potently stimulated mPAI-1 in kidney and spleen. LPS administration triggered robust expression of mPAI-1 in liver, kidney, pancreas, spleen and lung, while EGFP was induced only modestly in heart and kidney. These results indicate that the transcriptional response of the endogenous mPAI-1 promoter varies widely in terms of location and magnitude of response to specific stimuli. Moreover, the physiological regulation of PAI-1 expression likely involves a complex interaction of transcription factors and DNA sequences that are not adequately replicated by in vitro functional studies focused on the proximal -2.9 kb promoter.

The Palm-Heart Diameter: A Prospective Simple Screening Tool for Identifying Heart Enlargement

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Adegbenro Omotuyi John Fakoya

2017-11-01

CONCLUSION: This study establishes the correlation between the palm and heart diameters. Since the heart tissue and the upper limb share a similar embryonic origin, being the mesoderm, this study prospects the fact that heart enlargement could be preliminarily identified by measuring the size of the hand.

Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

DEFF Research Database (Denmark)

Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer

2008-01-01

Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

Embracing the heart: perioperative management of patients undergoing off-pump coronary artery bypass grafting using the octopus tissue stabilizer.

Science.gov (United States)

Nierich, A P; Diephuis, J; Jansen, E W; van Dijk, D; Lahpor, J R; Borst, C; Knape, J T

1999-04-01

To describe hemodynamic alterations during coronary artery bypass grafting (CABG) without extracorporeal circulation using the Octopus Tissue Stabilizer, and to describe the two anesthetic management protocols based on either general anesthesia with opioids (34 patients) or general anesthesia with high thoracic epidural anesthesia (TEA; 66 patients). A prospective observational report. An academic university heart center. First 100 patients undergoing CABG using the Octopus Tissue Stabilizer. None. Current management provided satisfactory results in preventing hypoperfusion of the heart and inadequate systemic circulation without the use of major pharmacologic interventions. Movement of the heart to reach the target site of anastomosis caused hemodynamic alterations. These could easily be corrected by anesthetic interventions, such as fluid load and low doses of inotropes. High TEA allows earlier extubation compared with the opioid anesthesia technique (0.9 v 4.5 hours). Perioperative management and the incidence of postoperative complications did not differ between anesthetic techniques. Major complications, such as death, intraoperative myocardial infarction, and stroke, did not occur. Both anesthetic protocols are safe and effective in handling these patients. Off-pump CABG surgery requires anesthetic interventions because hemodynamic alterations are caused by the presentation of the heart to the surgeon. The complication rate is low but needs to be evaluated, compared with conventional CABG, in a prospective randomized study. High thoracic epidural anesthesia allows early recovery, but improved outcome could not be proved in this patient group.

World Heart Day

Centers for Disease Control (CDC) Podcasts

2009-09-01

For World Heart Day, learn more about what heart-healthy steps you can take in the workplace.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

Eating Well While Dining Out: Collaborating with Local Restaurants to Promote Heart Healthy Menu Items

Science.gov (United States)

Thayer, Linden M.; Pimentel, Daniela C.; Smith, Janice C.; Garcia, Beverly A.; Lee Sylvester, Laura; Kelly, Tammy; Johnston, Larry F.; Ammerman, Alice S.; Keyserling, Thomas C.

2017-01-01

Background As Americans commonly consume restaurant foods with poor dietary quality, effective interventions are needed to improve food choices at restaurants. Purpose To design and evaluate a restaurant-based intervention to help customers select and restaurants promote heart healthy menu items with healthful fats and high quality carbohydrates. Methods The intervention included table tents outlining 10 heart healthy eating tips, coupons promoting healthy menu items, an information brochure, and link to study website. Pre and post intervention surveys were completed by restaurant managers and customers completed a brief “intercept” survey. Results Managers (n = 10) reported the table tents and coupons were well received, and several noted improved personal nutrition knowledge. Overall, 4214 coupons were distributed with 1244 (30%) redeemed. Of 300 customers surveyed, 126 (42%) noticed the table tents and of these, 115 (91%) considered the nutrition information helpful, 42 (33%) indicated the information influenced menu items purchased, and 91 (72%) reported the information will influence what they order in the future. Discussion The intervention was well-received by restaurant managers and positively influenced menu item selection by many customers. Translation to Health Education Practice Further research is needed to assess effective strategies for scaling up and sustaining this intervention approach. PMID:28947925

Neighborhood safety and adipose tissue distribution in African Americans: the Jackson Heart Study.

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Do Quyen Pham

Full Text Available Patterns of fat distribution are heavily influenced by psychological stress, sex, and among women, by menopause status. Emerging evidence suggests the lack of perceived neighborhood safety due to crime may contribute to psychological stress and obesity among exposed residents. Our objective is to determine if perceived neighborhood safety is associated with abdominal adiposity among African-American men and women, and among pre- and postmenopausal women in the Jackson Heart Study.We examined associations between perceived neighborhood safety, fat distribution, and other individual-level covariates among Jackson Heart Study participants (N = 2,881. Abdominal adiposity was measured via computed tomography scans measuring the volumes of visceral, subcutaneous and total adipose tissue. We also measured body mass index (BMI, and waist circumference. Multivariable regression models estimated associations between perceived neighborhood safety, adiposity, and covariates by sex and menopause status.Adjusting for all covariates, women who strongly disagreed their neighborhood was safe from crime had a higher BMI compared to women who felt safe [Std B 0.083 95% CI (0.010, 0.156]. Premenopausal women who felt most unsafe had higher BMI, waist circumference, and volumes of visceral and total adipose tissue than those who felt safe [Std B 0.160 (0.021, 0.299, Std B 0.142 (0.003, 0.280, Std B 0.150 (0.014, 0.285, Std B 0.154 (0.019, 0.290, respectively]. We did not identify associations between neighborhood safety and adiposity among men and postmenopausal women.Our data suggest that abdominal adipose tissue distribution patterns are associated with perceived neighborhood safety in some groups, and that patterns may differ by sex and menopause status, with most associations observed among pre-menopausal women. Further research is needed to elucidate whether there are causal mechanisms underlying sex and menopause-status differences that may mediate

Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

Science.gov (United States)

Boominathan, Vijay P; Ferreira, Tracie L

2012-12-01

Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise.

Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Wester, P O

1964-06-15

By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected.

Concentration of 24 Trace Elements in Human Heart Tissue Determined by Neutron Activation Analysis

International Nuclear Information System (INIS)

Wester, P.O.

1964-06-01

By means of neutron-activation analysis, human heart tissue from autopsy of 20 victims of traumatic accidents has been investigated with respect to the concentration of 24 different trace elements. A recently developed ion-exchange technique combined with gamma spectrometry has been used, which permits simultaneous determination of a large number of trace elements. The following trace elements have been determined quantitatively: Ag, As, Au, Ba, Br; Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Hg, La, Mo, Pt, Rb, Sb, Se, Se, Sm, Zn, W. In some heart samples, Hf and Os were determined qualitatively. The mean and standard deviation are given for the elements Cu, Fe, Se and Zn, Since none of the other quantitatively determined trace elements were normally distributed, the median is given as the central value. When possible, comparisons with values from other investigations have been made. No marked differences in the trace-element concentrations with age or sex could be detected

Periodontal bacteria DNA findings in human cardiac tissue - Is there a link of periodontitis to heart valve disease?

Science.gov (United States)

Ziebolz, D; Jahn, C; Pegel, J; Semper-Pinnecke, E; Mausberg, R F; Waldmann-Beushausen, R; Schöndube, F A; Danner, B C

2018-01-15

The aim of the study was to detect periodontal pathogens DNA in atrial and myocardial tissue, and to investigate periodontal status and their connection to cardiac tissue inflammation. In 30 patients, biopsy samples were taken from the atrium (A) and the ventricle myocardium (M) during aortic valve surgery. The dental examination included the dental and periodontal status (PS) and a collection of a microbiological sample. The detection of 11 periodontal pathogens DNA in oral and heart samples was carried out using PCR. The heart samples were prepared for detecting the LPS-binding protein (LBP), and for inflammation scoring on immunohistochemistry (IHC), comprising macrophages (CD68), LPS-binding protein receptor (CD14), and LBP (big42). 28 (93%) patients showed moderate to severe periodontitis. The periodontal pathogens in the oral samples of all patients revealed a similar distribution (3-93%). To a lesser extent and with a different distribution, these bacteria DNA were also detected in atrium and myocardium (3-27%). The LBP was detected in higher amount in atrium (0.22±0.16) versus myocardium (0.13±0.13, p=0.001). IHC showed a higher inflammation score in atrial than myocardial tissue as well as for CD14, CD68 and for LBP. Additional, periodontal findings showed a significant correlation to CD14 and CD68. The results provide evidence of the occurrence of oral bacteria DNA at the cardiac tissue, with a different impact on atrial and myocardial tissue inflammation. Influence of periodontal findings was identified, but their relevance is not yet distinct. Therefore further clinical investigations with long term implication are warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Melatonin promotes circadian rhythm-induced proliferation through Clock/histone deacetylase 3/c-Myc interaction in mouse adipose tissue.

Science.gov (United States)

Liu, Zhenjiang; Gan, Lu; Luo, Dan; Sun, Chao

2017-05-01

Melatonin is synthesized in the pineal gland and controls circadian rhythm of peripheral adipose tissue, resulting in changes in body weight. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm-mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20 mg/kg/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal1, Pcircadian locomotor output cycles kaput (Clock, Pcircadian disruption and promoted adipocyte proliferation in chronic jet-lagged mice and obese mice. Thus, our study found that melatonin promoted adipocyte proliferation by forming a Clock/HDAC3/c-Myc complex and subsequently driving the circadian amplitudes of proliferation genes. Our data reveal a novel mechanism that links circadian rhythm to cell proliferation in adipose tissue. These findings also identify a new potential means for melatonin to prevent and treat sleep deprivation-caused obesity. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Endogenous inotropic substance from heart tissue has digitalis-like properties

Energy Technology Data Exchange (ETDEWEB)

Khatter, J.C.; Agbanyo, M.; Navaratnam, S. (Univ. of Manitoba, Winnipeg (Canada))

1991-01-01

In the past few years, we developed an extraction procedure which we successfully used to isolate a crude fraction containing digitalis-like substance (DLS) from porcine left ventricular tissue. In this study, the crude fraction was found to cross-react with digoxin antibodies and showed immunoreactivity of 4.25 {plus minus} 0.6 ng digoxin equivalent/ml. On further purification of the crude fraction using silica gel G column chromatography, a fraction C was obtained, which was highly positive inotropic on canine trabeculae and it dose-dependently inhibited ouabain sensitive {sup 86}Rb{sup +} uptake in rate heart slices. A 50% inhibition of uptake was obtained by 25 ul of fraction C. Fraction C also inhibited canine kidney Na{sup +}, K{sup +}-ATPase dose-dependently and a 50% inhibition of this enzyme required 17 ul of fraction C. Ashing of the fraction C at 500{degree}C resulted in loss of inotropic and enzyme inhibitory activities, indicating an organic nature of the unknown digitalis-like substance.

Salud Para Su Corazon-NCLR: a comprehensive Promotora outreach program to promote heart-healthy behaviors among hispanics.

Science.gov (United States)

Balcazar, Hector; Alvarado, Matilde; Hollen, Mary Luna; Gonzalez-Cruz, Yanira; Hughes, Odelinda; Vazquez, Esperanza; Lykens, Kristine

2006-01-01

This article describes results of year-1 implementation of the Salud Para Su Corazón (Health For Your Heart)-National Council of la Raza (NCLR) promotora (lay health worker) program for promoting heart-healthy behaviors among Latinos. Findings of this community outreach initiative include data from promotora pledges and self-skill behaviors, cardiovascular disease risk factors of Latino families, family heart-health education delivery, and program costs associated with promotora time. Participation included 29 trained promotoras serving 188 families from three NCLR affiliates in Escondido, California; Chicago, Illinois; and Ojo Caliente, New Mexico. Using several evaluation tools, the results showed that the promotora approach worked based on evidence obtained from the following indicators: changes in promotora's pre-post knowledge and performance skills, progress toward their pledge goals following training, recruiting and teaching families, providing follow-up, and organizing or participating in community events. Strengths and limitations of the promotora model approach are also discussed.

Noncanonical Wnt signaling promotes obesity-induced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion.

Science.gov (United States)

Fuster, José J; Zuriaga, María A; Ngo, Doan Thi-Minh; Farb, Melissa G; Aprahamian, Tamar; Yamaguchi, Terry P; Gokce, Noyan; Walsh, Kenneth

2015-04-01

Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Cell culture studies and gain-of-function mouse models suggest that canonical Wnt proteins modulate adipose tissue expansion. However, no genetic evidence supports a role for endogenous Wnt proteins in adipose tissue dysfunction, and the role of noncanonical Wnt signaling remains largely unexplored. Here we provide evidence from human, mouse, and cell culture studies showing that Wnt5a-mediated, noncanonical Wnt signaling contributes to obesity-associated metabolic dysfunction by increasing adipose tissue inflammation. Wnt5a expression is significantly upregulated in human visceral fat compared with subcutaneous fat in obese individuals. In obese mice, Wnt5a ablation ameliorates insulin resistance, in parallel with reductions in adipose tissue inflammation. Conversely, Wnt5a overexpression in myeloid cells augments adipose tissue inflammation and leads to greater impairments in glucose homeostasis. Wnt5a ablation or overexpression did not affect fat mass or adipocyte size. Mechanistically, Wnt5a promotes the expression of proinflammatory cytokines by macrophages in a Jun NH2-terminal kinase-dependent manner, leading to defective insulin signaling in adipocytes. Exogenous interleukin-6 administration restores insulin resistance in obese Wnt5a-deficient mice, suggesting a central role for this cytokine in Wnt5a-mediated metabolic dysfunction. Taken together, these results demonstrate that noncanonical Wnt signaling contributes to obesity-induced insulin resistance independent of adipose tissue expansion. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction

Science.gov (United States)

Ma, Yonggang; Mouton, Alan J.; Lindsey, Merry L.

2018-01-01

Macrophages play critical roles in homeostatic maintenance of the myocardium under normal conditions and in tissue repair after injury. In the steady-state heart, resident cardiac macrophages remove senescent and dying cells and facilitate electrical conduction. In the aging heart, the shift in macrophage phenotype to a proinflammatory subtype leads to inflammaging. Following myocardial infarction (MI), macrophages recruited to the infarct produce both proinflammatory and anti-inflammatory mediators (cytokines, chemokines, matrix metalloproteinases, and growth factors), phagocytize dead cells, and promote angiogenesis and scar formation. These diverse properties are attributed to distinct macrophage subtypes and polarization status. Infarct macrophages exhibit a proinflammatory M1 phenotype early and become polarized toward an anti-inflammatory M2 phenotype later post- MI. Although this classification system is oversimplified and needs to be refined to accommodate the multiple different macrophage subtypes that have been recently identified, general concepts on macrophage roles are independent of subtype classification. This review summarizes current knowledge about cardiac macrophage origins, roles, and phenotypes in the steady state, with aging, and after MI, as well as highlights outstanding areas of investigation. PMID:29106912

(S)Partners for Heart Health: a school-based program for enhancing physical activity and nutrition to promote cardiovascular health in 5th grade students.

Science.gov (United States)

Carlson, Joseph J; Eisenmann, Joey C; Pfeiffer, Karin A; Jager, Kathleen B; Sehnert, Scott T; Yee, Kimbo E; Klavinski, Rita A; Feltz, Deborah L

2008-12-22

The American Heart Association Position Statement on Cardiovascular Health Promotion in Public Schools encourages school-based interventions for the primary prevention of cardiovascular disease (CVD) through risk factor prevention or reduction in children with an emphasis on creating an environment that promotes healthy food choices and physical activity (PA). In an effort to address issues related to CVD risk factors including obesity in Michigan children, a multi-disciplinary team of Michigan State University (MSU) faculty, clinicians, and health profession students was formed to "(S)partner" with elementary school physical education (PE) teachers and MSU Extension staff to develop and implement a cost-effective, sustainable program aimed at CVD risk factor prevention and management for 5th grade students. This (S)partnership is intended to augment and improve the existing 5th grade PE, health and nutrition curriculum by achieving the following aims: 1) improve the students' knowledge, attitudes and confidence about nutrition, PA and heart health; 2) increase the number of students achieving national recommendations for PA and nutrition; and 3) increase the number of students with a desirable CVD risk factor status based on national pediatric guidelines. Secondary aims include promoting school staff and parental support for heart health to help children achieve their goals and to provide experiential learning and service for MSU health profession students for academic credit. This pilot effectiveness study was approved by the MSU IRB. At the beginning and the end of the school year students undergo a CVD risk factor assessment conducted by MSU medical students and graduate students. Key intervention components include eight lesson plans (conducted bi-monthly) designed to promote heart healthy nutrition and PA behaviors conducted by PE teachers with assistance from MSU undergraduate dietetic and kinesiology students (Spartners). The final 10 minutes of each lesson

IGRT of the breast : doses to contralateral breast, heart and other untargeted tissues

International Nuclear Information System (INIS)

Taylor, M.L.; Lye, J.E.; Franich, R.D.

2011-01-01

Full text: Radiotherapy has an important role to play in locoregional therapy after surgery, particularly in reducing the likelihood of local recurrence. While there is no doubt about the benefit of adjuvant radiotherapy, concerns have been raised about radiation induced secondary cancers in the contralateral breast, lung and-if the left breast is treated-damage to the heart. We recently showed that Monte Carlo methods may be the most appropriate means for determination of such out-of-field doses to healthy tissues at intermediate distances from the primary field (J Med Phys 36 (20 I I) 59-71). A detailed, dosimetrically-matched Monte Carlo model of a Varian 21iX linear accelerator with mounted Varian G242 KV cone-beam computed tomography (CBCT) unit was constructed based on comprehensive manufacturer specifications. Patient CT scans were converted to voxelised phantoms and real treatment plans were replicated in silico. Doses to out of- field healthy structures (such as breast, heart and lung) were evaluated and risks of radiocarcinogenesis and cardiotoxicity estimated. It is possible to vary kV imager blade openings to influence out-of-field doses and associated risks.

Modeling collagen remodeling in tissue engineered cardiovascular tissues

NARCIS (Netherlands)

Soares, A.L.F.

2012-01-01

Commonly, heart valve replacements consist of non-living materials lacking the ability to grow, repair and remodel. Tissue engineering (TE) offers a promising alternative to these replacement strategies since it can overcome its disadvantages. The technique aims to create an autologous living tissue

Inhibition of Notch signaling by Dll4-Fc promotes reperfusion of acutely ischemic tissues

Energy Technology Data Exchange (ETDEWEB)

Liu, Ren [Department of Pathology, University of Southern California, Los Angeles (United States); Trindade, Alexandre [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Sun, Zhanfeng [Department of Vascular Surgery, 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang (China); Kumar, Ram; Weaver, Fred A. [Department of Surgery, University of Southern California, Los Angeles (United States); Krasnoperov, Valery; Naga, Kranthi [Vasgene Therapeutics, Los Angeles, CA (United States); Duarte, Antonio [Centro Interdisciplinar de Investigacao em Sanidade Animal (CIISA), Lisbon Technical University, Lisbon (Portugal); Instituto Gulbenkian de Ciencia, Oeiras (Portugal); Gill, Parkash S., E-mail: parkashg@usc.edu [Department of Pathology, University of Southern California, Los Angeles (United States)

2012-02-03

Highlights: Black-Right-Pointing-Pointer Low dose Dll4-Fc increases vascular proliferation and overall perfusion. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in hindlimb ischemia model. Black-Right-Pointing-Pointer Low dose Dll4-Fc helps vascular injury recovery in skin flap model. Black-Right-Pointing-Pointer Dll4 heterozygous deletion promotes vascular injury recovery. Black-Right-Pointing-Pointer Dll4 overexpression delays vascular injury recovery. -- Abstract: Notch pathway regulates vessel development and maturation. Dll4, a high-affinity ligand for Notch, is expressed predominantly in the arterial endothelium and is induced by hypoxia among other factors. Inhibition of Dll4 has paradoxical effects of reducing the maturation and perfusion in newly forming vessels while increasing the density of vessels. We hypothesized that partial and/or intermittent inhibition of Dll4 may lead to increased vascular response and still allow vascular maturation to occur. Thus tissue perfusion can be restored rapidly, allowing quicker recovery from ischemia or tissue injury. Our studies in two different models (hindlimb ischemia and skin flap) show that inhibition of Dll4 at low dose allows faster recovery from vascular and tissue injury. This opens a new possibility for Dll4 blockade's therapeutic application in promoting recovery from vascular injury and restoring blood supply to ischemic tissues.

(SPartners for Heart Health: a school-based program for enhancing physical activity and nutrition to promote cardiovascular health in 5th grade students

Directory of Open Access Journals (Sweden)

Sehnert Scott T

2008-12-01

Full Text Available Abstract Background The American Heart Association Position Statement on Cardiovascular Health Promotion in Public Schools encourages school-based interventions for the primary prevention of cardiovascular disease (CVD through risk factor prevention or reduction in children with an emphasis on creating an environment that promotes healthy food choices and physical activity (PA. In an effort to address issues related to CVD risk factors including obesity in Michigan children, a multi-disciplinary team of Michigan State University (MSU faculty, clinicians, and health profession students was formed to "(Spartner" with elementary school physical education (PE teachers and MSU Extension staff to develop and implement a cost-effective, sustainable program aimed at CVD risk factor prevention and management for 5th grade students. This (Spartnership is intended to augment and improve the existing 5th grade PE, health and nutrition curriculum by achieving the following aims: 1 improve the students' knowledge, attitudes and confidence about nutrition, PA and heart health; 2 increase the number of students achieving national recommendations for PA and nutrition; and 3 increase the number of students with a desirable CVD risk factor status based on national pediatric guidelines. Secondary aims include promoting school staff and parental support for heart health to help children achieve their goals and to provide experiential learning and service for MSU health profession students for academic credit. Methods/Design This pilot effectiveness study was approved by the MSU IRB. At the beginning and the end of the school year students undergo a CVD risk factor assessment conducted by MSU medical students and graduate students. Key intervention components include eight lesson plans (conducted bi-monthly designed to promote heart healthy nutrition and PA behaviors conducted by PE teachers with assistance from MSU undergraduate dietetic and kinesiology students

Factors Facilitating the Implementation of Church-Based Heart Health Promotion Programs for Older Adults: A Qualitative Study Guided by the Precede-Proceed Model.

Science.gov (United States)

Banerjee, Ananya Tina; Kin, R; Strachan, Patricia H; Boyle, Michael H; Anand, Sonia S; Oremus, Mark

2015-01-01

To describe the factors facilitating the implementation of heart health promotion programs for older adults in Anglican, United, and Catholic churches. The study used qualitative methods comprising semistructured interviews and focus groups. The interviews and focus groups were conducted in Anglican, Catholic, and United churches located in the Canadian cities of Toronto and Hamilton, Ontario. Twelve ordained pastors and 21 older parishioners who attended church regularly and who had no health conditions were recruited to best explain how churches could be suitable locations for health promotion activities targeting older adults. Twelve semistructured interviews with the pastors and three focus groups with the 21 parishioners were undertaken. A component of the Precede-Proceed model (a model for planning health education and health promotion programs and policies) was applied to the findings after direct content analysis of the data. Participants identified pastor leadership, funding for a parish nurse, community-focused interventions, secured infrastructure, and social support from congregation members as pertinent factors required for implementing health promotion programs in Anglican, United, and Catholic churches. The findings have particular relevance for health promotion and public health because they suggest factors that would be necessary to design church-based heart health promotion programs for older adults at risk of chronic diseases.

Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration.

Science.gov (United States)

Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2016-01-01

Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema.

Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study

DEFF Research Database (Denmark)

Gram, J; Bladbjerg, E-M; Møller, L

2000-01-01

OBJECTIVES: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects. DESIGN: Nested case-control study. Follow-up periods 7-15 years. SUBJECTS: Included in the study were 133 cases with coronary heart disease...... and 258 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum.......005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out...

Mechanical Stretching Promotes Skin Tissue Regeneration via Enhancing Mesenchymal Stem Cell Homing and Transdifferentiation.

Science.gov (United States)

Liang, Xiao; Huang, Xiaolu; Zhou, Yiwen; Jin, Rui; Li, Qingfeng

2016-07-01

Skin tissue expansion is a clinical procedure for skin regeneration to reconstruct cutaneous defects that can be accompanied by severe complications. The transplantation of mesenchymal stem cells (MSCs) has been proven effective in promoting skin expansion and helping to ameliorate complications; however, systematic understanding of its mechanism remains unclear. MSCs from luciferase-Tg Lewis rats were intravenously transplanted into a rat tissue expansion model to identify homing and transdifferentiation. To clarify underlying mechanisms, a systematic approach was used to identify the differentially expressed genes between mechanically stretched human MSCs and controls. The biological significance of these changes was analyzed through bioinformatic methods. We further investigated genes and pathways of interest to disclose their potential role in mechanical stretching-induced skin regeneration. Cross sections of skin samples from the expanded group showed significantly more luciferase(+) and stromal cell-derived factor 1α (SDF-1α)(+), luciferase(+)keratin 14(+), and luciferase(+)CD31(+) cells than the control group, indicating MSC transdifferentiation into epidermal basal cells and endothelial cells after SDF-1α-mediated homing. Microarray analysis suggested upregulation of genes related to hypoxia, vascularization, and cell proliferation in the stretched human MSCs. Further investigation showed that the homing of MSCs was blocked by short interfering RNA targeted against matrix metalloproteinase 2, and that mechanical stretching-induced vascular endothelial growth factor A upregulation was related to the Janus kinase/signal transducer and activator of transcription (Jak-STAT) and Wnt signaling pathways. This study determines that mechanical stretching might promote skin regeneration by upregulating MSC expression of genes related to hypoxia, vascularization, and cell proliferation; enhancing transplanted MSC homing to the expanded skin; and

Control of an air pressure actuated disposable bioreactor for cultivating heart valves

NARCIS (Netherlands)

Beelen, M.J.; Neerincx, P.E.; Molengraft, van de M.J.G.

2011-01-01

A disposable injection molded bioreactor for growing tissue-engineered heart valves is controlled to mimic the physiological heart cycle. Tissue-engineered heart valves, cultured from human stem cells, are a possible alternative for replacing failing aortic heart valves, where nowadays biological

Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue

Science.gov (United States)

Boengler, Kerstin; Kosiol, Maik; Mayr, Manuel; Schulz, Rainer

2017-01-01

Abstract Age is the most important risk factor for most diseases. Mitochondria play a central role in bioenergetics and metabolism. In addition, several lines of evidence indicate the impact of mitochondria in lifespan determination and ageing. The best‐known hypothesis to explain ageing is the free radical theory, which proposes that cells, organs, and organisms age because they accumulate reactive oxygen species (ROS) damage over time. Mitochondria play a central role as the principle source of intracellular ROS, which are mainly formed at the level of complex I and III of the respiratory chain. Dysfunctional mitochondria generating less ATP have been observed in various aged organs. Mitochondrial dysfunction comprises different features including reduced mitochondrial content, altered mitochondrial morphology, reduced activity of the complexes of the electron transport chain, opening of the mitochondrial permeability transition pore, and increased ROS formation. Furthermore, abnormalities in mitochondrial quality control or defects in mitochondrial dynamics have also been linked to senescence. Among the tissues affected by mitochondrial dysfunction are those with a high‐energy demand and thus high mitochondrial content. Therefore, the present review focuses on the impact of mitochondria in the ageing process of heart and skeletal muscle. In this article, we review different aspects of mitochondrial dysfunction and discuss potential therapeutic strategies to improve mitochondrial function. Finally, novel aspects of adipose tissue biology and their involvement in the ageing process are discussed. PMID:28432755

Social media for health promotion: What messages are women receiving about cardiovascular disease risk by the Canadian Heart and Stroke Foundation?

Science.gov (United States)

Gonsalves, Christine A; McGannon, Kerry R; Schinke, Robert J

2017-11-01

The aim of this study was to explore the meanings of women's cardiovascular disease constructed within the Canadian Heart and Stroke Foundation Facebook page. Posts from Heart and Stroke Foundation and public user comments surrounding the launch of the Heart and Stroke Foundation re-branding were of interest. Ethnographic content analysis was employed to analyse text ( n = 40), images ( n = 32), videos ( n = 6), user comments and replies ( n = 42) from November 2016 to March 2017. Constructions (re)presented on Facebook of 'typical' women at risk and risk reduction were problematic as women most at risk were excluded through the use of consumerist, medicalized identities which also excluded promotion of healthy behaviour changes.

Restoration of heart functions using human embryonic stem cells derived heart muscle cells.

Science.gov (United States)

Gepstein, Lior; Kehat, Izhak

2005-02-01

Extract: Recent advances in molecular and cellular biology and specifically in the areas of stem cell biology and tissue engineering have paved the way for the development of a new field in biomedicine, regenerative medicine. This exciting approach seeks to develop new biological solutions, using the mobilization of endogenous stem cells or delivery of exogenous cells to replace or modify the function of diseased, absent, or malfunctioning tissue. The adult heart represents an attractive candidate for these emerging technologies, since adult cardiomyocytes have limited regenerative capacity. Thus, any significant heart cell loss or dysfunction, such as occurs during heart attack, is mostly irreversible and may lead to the development of progressive heart failure, one of the leading causes of world-wide morbidity and mortality. Similarly, dysfunction of the specialized electrical conduction system within the heart may result in inefficient rhythm initiation or impulse conduction, leading to significant slowing of the heart rate, usually requiring the implantation of a permanent electronic pacemaker. Replacement of the dysfunctional myocardium (heart muscle) by implantation of external heart muscle cells is emerging as a novel paradigm for restoration of the myocardial electromechanical properties, but has been significantly hampered by the paucity of cell sources for human heart cells and by the relatively limited evidence for functional integration between grafted and host cells. The recently described human embryonic stem cell (hESC) lines may provide a possible solution for the aforementioned cell sourcing problem.

Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering.

Science.gov (United States)

Zhang, Xing; Xu, Bin; Puperi, Daniel S; Yonezawa, Aline L; Wu, Yan; Tseng, Hubert; Cuchiara, Maude L; West, Jennifer L; Grande-Allen, K Jane

2015-03-01

The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats.

Science.gov (United States)

Kim, Junhwan; Villarroel, José Paul Perales; Zhang, Wei; Yin, Tai; Shinozaki, Koichiro; Hong, Angela; Lampe, Joshua W; Becker, Lance B

2016-01-01

Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

Preparation of degradable porous structures based on 1,3-trimethylene carbonate and D,L-lactide (co)polymers for heart tissue engineering

NARCIS (Netherlands)

Pego, AP; Siebum, B; Van Luyn, MJA; Van Seijen, XJGY; Poot, AA; Grijpma, DW; Feijen, J

2003-01-01

Biodegradable porous scaffolds for heart tissue engineering were prepared from amorphous elastomeric (co)polymers of 1,3-trimethylene carbonate (TMC) and D,L-lactide (DLLA). Leaching of salt from compression-molded polymer-salt composites allowed the preparation of highly porous structures in a

Stem cell death and survival in heart regeneration and repair.

Science.gov (United States)

Abdelwahid, Eltyeb; Kalvelyte, Audrone; Stulpinas, Aurimas; de Carvalho, Katherine Athayde Teixeira; Guarita-Souza, Luiz Cesar; Foldes, Gabor

2016-03-01

Cardiovascular diseases are major causes of mortality and morbidity. Cardiomyocyte apoptosis disrupts cardiac function and leads to cardiac decompensation and terminal heart failure. Delineating the regulatory signaling pathways that orchestrate cell survival in the heart has significant therapeutic implications. Cardiac tissue has limited capacity to regenerate and repair. Stem cell therapy is a successful approach for repairing and regenerating ischemic cardiac tissue; however, transplanted cells display very high death percentage, a problem that affects success of tissue regeneration. Stem cells display multipotency or pluripotency and undergo self-renewal, however these events are negatively influenced by upregulation of cell death machinery that induces the significant decrease in survival and differentiation signals upon cardiovascular injury. While efforts to identify cell types and molecular pathways that promote cardiac tissue regeneration have been productive, studies that focus on blocking the extensive cell death after transplantation are limited. The control of cell death includes multiple networks rather than one crucial pathway, which underlies the challenge of identifying the interaction between various cellular and biochemical components. This review is aimed at exploiting the molecular mechanisms by which stem cells resist death signals to develop into mature and healthy cardiac cells. Specifically, we focus on a number of factors that control death and survival of stem cells upon transplantation and ultimately affect cardiac regeneration. We also discuss potential survival enhancing strategies and how they could be meaningful in the design of targeted therapies that improve cardiac function.

Heart Age PSA (:60)

Centers for Disease Control (CDC) Podcasts

2015-09-01

This 60 second public service announcement is based on the September 2015 CDC Vital Signs report. Your heart age is the age of your heart and blood vessels as a result of your risk factors for heart attack and stroke. If you smoke or have high blood pressure, your heart age will be much higher than your actual age. Learn what you can do to lower your heart age and keep it low.  Created: 9/1/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/1/2015.

3D confocal imaging in CUBIC-cleared mouse heart

Energy Technology Data Exchange (ETDEWEB)

Nehrhoff, I.; Bocancea, D.; Vaquero, J.; Vaquero, J.J.; Lorrio, M.T.; Ripoll, J.; Desco, M.; Gomez-Gaviro, M.V.

2016-07-01

Acquiring high resolution 3D images of the heart enables the ability to study heart diseases more in detail. Here, the CUBIC (clear, unobstructed brain imaging cocktails and computational analysis) clearing protocol was adapted for thick mouse heart sections to increase the penetration depth of the confocal microscope lasers into the tissue. The adapted CUBIC clearing of the heart lets the antibody penetrate deeper into the tissue by a factor of five. The here shown protocol enables deep 3D highresolution image acquisition in the heart. This allows a much more accurate assessment of the cellular and structural changes that underlie heart diseases. (Author)

3D confocal imaging in CUBIC-cleared mouse heart

International Nuclear Information System (INIS)

Nehrhoff, I.; Bocancea, D.; Vaquero, J.; Vaquero, J.J.; Lorrio, M.T.; Ripoll, J.; Desco, M.; Gomez-Gaviro, M.V.

2016-01-01

Acquiring high resolution 3D images of the heart enables the ability to study heart diseases more in detail. Here, the CUBIC (clear, unobstructed brain imaging cocktails and computational analysis) clearing protocol was adapted for thick mouse heart sections to increase the penetration depth of the confocal microscope lasers into the tissue. The adapted CUBIC clearing of the heart lets the antibody penetrate deeper into the tissue by a factor of five. The here shown protocol enables deep 3D highresolution image acquisition in the heart. This allows a much more accurate assessment of the cellular and structural changes that underlie heart diseases. (Author)

Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

International Nuclear Information System (INIS)

Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

2014-01-01

Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

Peculiarities of cardiac hemodynamics and functional state of left ventricular myocardium in teenagers with connective heart tissue dysplasia

Directory of Open Access Journals (Sweden)

Makhmudova F.M.

2011-03-01

Full Text Available The aim of investigation is to study heart hemodynamics in teenagers with connective tissue dysplasia of heart (CTDH. 35 patients ages 12 to 15 years with CTDH have been observed: Group I (n=14 are the patients with mitral valve prolapse (MVP without mitral regurgitation (MR and myxomatous degeneration(MD or isolated minor heart abnormalities (MHA, Group II (n=11are patients with MVP and MR in combination with 1 or2 MHA, and Group III (n=10 are patients with MVP and mixoid degeneration (MD in combination with 2 or more MHA. The control group consisted of 15 patients of the same age without MHA. All the children passed Doppler and echocardiography. According to the results significant changes of cardiohemodynamic indices in patients of Group I were not observed. The changes of size and volume indices of the left ventricle (LV, increase in wall thickness and diastolic dysfunction of the LV were observed in Group II. The significant changes of systolic function of left ventricular myocardium were observed in Group III. The study comes to the conclusion that teenagers with CTDH have definite changes of heart hemodynamics and functional state of left ventricular myocardium. These changes depend on mitral regurgitation, myxomatous degeneration and MHA combination

Validation of persuasive messages for the promotion of physical activity among people with coronary heart disease.

Science.gov (United States)

Mendez, Roberto Della Rosa; Rodrigues, Roberta Cunha Matheus; Spana, Thaís Moreira; Cornélio, Marília Estevam; Gallani, Maria Cecília Bueno Jayme; Pérez-Nebra, Amalia Raquel

2012-01-01

to validate the content of persuasive messages for promoting walking among patients with coronary heart disease (CHD). The messages were constructed to strengthen or change patients' attitudes to walking. the selection of persuasive arguments was based on behavioral beliefs (determinants of attitude) related to walking. The messages were constructed based in the Elaboration Likelihood Model and were submitted to content validation. the data was analyzed with the content validity index and by the importance which the patients attributed to the messages' persuasive arguments. Positive behavioral beliefs (i.e. positive and negative reinforcement) and self-efficacy were the appeals which the patients considered important. The messages with validation evidence will be tested in an intervention study for the promotion of the practice of physical activity among patients with CHD.

Radiochemicals used to scan the heart

International Nuclear Information System (INIS)

Anon.

1975-01-01

Techniques for heart scanning using 201 Tl and /sup 99m/Tc pyrophosphate are discussed. Thallium-201, produced artificially in a cyclotron, concentrates in normal heart muscle but not in abnormal tissue. Technetium-99m is deposited in mitochondria of heart cells that are irreversibly damaged. The combined use of 201 Tl and /sup 99m/Tc makes it possible to identify regions of recent heart damage as well as older heart damage. Advantages of using 129 Cs for heart scanning are also discussed

The Responses of Tissues from the Brain, Heart, Kidney, and Liver to Resuscitation following Prolonged Cardiac Arrest by Examining Mitochondrial Respiration in Rats

Directory of Open Access Journals (Sweden)

Junhwan Kim

2016-01-01

Full Text Available Cardiac arrest induces whole-body ischemia, which causes damage to multiple organs. Understanding how each organ responds to ischemia/reperfusion is important to develop better resuscitation strategies. Because direct measurement of organ function is not practicable in most animal models, we attempt to use mitochondrial respiration to test efficacy of resuscitation on the brain, heart, kidney, and liver following prolonged cardiac arrest. Male Sprague-Dawley rats are subjected to asphyxia-induced cardiac arrest for 30 min or 45 min, or 30 min cardiac arrest followed by 60 min cardiopulmonary bypass resuscitation. Mitochondria are isolated from brain, heart, kidney, and liver tissues and examined for respiration activity. Following cardiac arrest, a time-dependent decrease in state-3 respiration is observed in mitochondria from all four tissues. Following 60 min resuscitation, the respiration activity of brain mitochondria varies greatly in different animals. The activity after resuscitation remains the same in heart mitochondria and significantly increases in kidney and liver mitochondria. The result shows that inhibition of state-3 respiration is a good marker to evaluate the efficacy of resuscitation for each organ. The resulting state-3 respiration of brain and heart mitochondria following resuscitation reenforces the need for developing better strategies to resuscitate these critical organs following prolonged cardiac arrest.

CDC Vital Signs-Heart Age

Centers for Disease Control (CDC) Podcasts

2015-09-01

This podcast is based on the September 2015 CDC Vital Signs report. Your heart age is the age of your heart and blood vessels as a result of your risk factors for heart attack and stroke. If you smoke or have high blood pressure, your heart age will be much higher than your actual age. Learn what you can do to lower your heart age and keep it low.  Created: 9/1/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/1/2015.

Establishing the framework to support bioartificial heart fabrication using fibrin-based three-dimensional artificial heart muscle.

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Hogan, Matthew; Mohamed, Mohamed; Tao, Ze-Wei; Gutierrez, Laura; Birla, Ravi

2015-02-01

Only 3000 heart transplants are performed in the USA every year, leaving some 30 000-70 000 Americans without proper care. Current treatment modalities for heart failure have saved many lives yet still do not correct the underlying problems of congestive heart failure. Tissue engineering represents a potential field of study wherein a combination of cells, scaffolds, and/or bioreactors can be utilized to create constructs to mimic, replace, and/or repair defective tissue. The focus of this study was to generate a bioartificial heart (BAH) model using artificial heart muscle (AHM), composed of fibrin gel and neonatal rat cardiac myocytes, and a decellularized scaffold, formed by subjecting an adult rat heart to a series of decellularization solutions. By suturing the AHM around the outside of the decellularized heart and culturing while suspended in media, we were able to retain functional cardiac cells on the scaffold as evinced by visible contractility. Observed contractility rate was correlated with biopotential measurements to confirm essential functionality of cardiac constructs. Cross-sections of the BAH show successful decellularization of the scaffold and contiguous cell-rich AHM around the perimeter of the heart. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

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Ichikawa, Tomohiro [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Sugiura, Hisatoshi, E-mail: sugiura@rm.med.tohoku.ac.jp [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan); Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki [Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-8509 (Japan); Ichinose, Masakazu [Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574 (Japan)

2013-05-01

Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P<0.001) and collagen I (P<0.001) expression in HFL-1. 25-HC also significantly enhanced the release and activation of matrix metallaoproteinase (MMP)-2 (P<0.001) and MMP-9 (P<0.001) without any significant effect on the production of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. 25-HC stimulated transforming growth factor (TGF)-β{sub 1} production (P<0.01) and a neutralizing anti-TGF-β antibody restored these 25-HC-augmented pro-fibrotic responses. 25-HC significantly promoted the translocation of nuclear factor (NF)-κB p65 into the nuclei (P<0.01), but not phospholylated-c-jun, a complex of activator protein-1. Pharmacological inhibition of NF-κB restored the 25-HC-augmented pro-fibrotic responses and TGF-β{sub 1} release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway.

Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

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Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

2017-09-01

Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

Kojyl cinnamate ester derivatives promote adiponectin production during adipogenesis in human adipose tissue-derived mesenchymal stem cells.

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Rho, Ho Sik; Hong, Soo Hyun; Park, Jongho; Jung, Hyo-Il; Park, Young-Ho; Lee, John Hwan; Shin, Song Seok; Noh, Minsoo

2014-05-01

The subcutaneous fat tissue mass gradually decreases with age, and its regulation is a strategy to develop anti-aging compounds to ameliorate the photo-aging of human skin. The adipogenesis of human adipose tissue-mesenchymal stem cells (hAT-MSCs) can be used as a model to discover novel anti-aging compounds. Cinnamomum cassia methanol extracts were identified as adipogenesis-promoting agents by natural product library screening. Cinnamates, the major chemical components of Cinnamomum cassia extracts, promoted adipogenesis in hAT-MSCs. We synthesized kojyl cinnamate ester derivatives to improve the pharmacological activity of cinnamates. Structure-activity studies of kojyl cinnamate derivatives showed that both the α,β-unsaturated carbonyl ester group and the kojic acid moiety play core roles in promoting adiponectin production during adipogenesis in hAT-MSCs. We conclude that kojyl cinnamate ester derivatives provide novel pharmacophores that can regulate adipogenesis in hAT-MSCs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of hope promoting interventions based on religious beliefs on quality of life of patients with congestive heart failure and their families

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Binaei, Niloufar; Moeini, Mahin; Sadeghi, Masoumeh; Najafi, Mostafa; Mohagheghian, Zahra

2016-01-01

Background: Heart failure is one of the most important and prevalent diseases that may have negative effects on the quality of life (QOL). Today, the promotion of QOL in patients with heart failure is important in nursing care programs. This research aimed to determine the efficacy of hope-promoting interventions based on religious beliefs on the QOL of patients with congestive heart failure (CHF). Materials and Methods: In this randomized clinical trial (IRCT2014100619413N1) conducted in Isfahan, Iran, 46 adult patients with CHF were selected and randomly assigned to study and control groups. Ferrans and Powers Quality of Life Index (QLI) was completed by both groups before, immediately after, and 1 month after the intervention. For the study group participants and their families, 60-min sessions of hope-promoting interventions based on religious beliefs were held twice a week for 3 weeks. Independent t, repeated measures analysis of variance (ANOVA), Chi-square, Mann–Whitney, and Fisher's exact tests were adopted for data analysis. Results: The mean (standard deviation) overall QOL score in the area of satisfaction significantly increased in the study group, compared to the controls, immediately [70.7 (8.5) vs. 59.2 (12.5)] and 1 month after the intervention [75.2 (7.4) vs. 59.4 (12.9)] (P < 0.05). There was also a similar difference between the two groups in the area of importance immediately [73.6 (5.8) vs. 65.7 (7.5)] and 1 month after the intervention [76.3 (8.1) vs. 66.8 (8.5)] (P < 0.05). Conclusions: Hope-promoting intervention based on religious beliefs is a useful method for improving QOL in patients with CHF. PMID:26985226

Effects of Re-heating Tissue Samples to Core Body Temperature on High-Velocity Ballistic Projectile-tissue Interactions.

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Humphrey, Caitlin; Henneberg, Maciej; Wachsberger, Christian; Maiden, Nicholas; Kumaratilake, Jaliya

2017-11-01

Damage produced by high-speed projectiles on organic tissue will depend on the physical properties of the tissues. Conditioning organic tissue samples to human core body temperature (37°C) prior to conducting ballistic experiments enables their behavior to closely mimic that of living tissues. To minimize autolytic changes after death, the tissues are refrigerated soon after their removal from the body and re-heated to 37°C prior to testing. This research investigates whether heating 50-mm-cube samples of porcine liver, kidney, and heart to 37°C for varying durations (maximum 7 h) can affect the penetration response of a high-speed, steel sphere projectile. Longer conditioning times for heart and liver resulted in a slight loss of velocity/energy of the projectile, but the reverse effect occurred for the kidney. Possible reasons for these trends include autolytic changes causing softening (heart and liver) and dehydration causing an increase in density (kidney). © 2017 American Academy of Forensic Sciences.

Antibody formation towards porcine tissue in patients implanted with crosslinked heart valves is directed to antigenic tissue proteins and αGal epitopes and is reduced in healthy vegetarian subjects.

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Böer, Ulrike; Buettner, Falk F R; Schridde, Ariane; Klingenberg, Melanie; Sarikouch, Samir; Haverich, Axel; Wilhelmi, Mathias

2017-03-01

Glutaraldehyde-fixed porcine heart valves (ga-pV) are one of the most frequently used substitutes for insufficient aortic and pulmonary heart valves which, however, degenerate after 10-15 years. Yet, xeno-immunogenicity of ga-pV in humans including identification of immunogens still needs to be investigated. We here determined the immunogenicity of ga-pV in patients with respect to antibody formation, identity of immunogens and potential options to reduce antibody levels. Levels of tissue-specific and anti-αGal antibodies were determined retrospectively in patients who received ga-pV for 51 months (n=4), 25 months (n=6) or 5 months (n=4) and compared to age-matched untreated subjects (n=10) or younger subjects with or without vegetarian diet (n=12/15). Immunogenic proteins were investigated by Western blot approaches. Tissue-specific antibodies in patients were elevated after 5 (1.73-fold) and 25 (1.46-fold, both PVegetarian diet reduced significantly (0.63-fold, P<.01) the level of pre-formed αGal but not of tissue-specific antibodies. Immune response in patients towards ga-pV is induced by the porcine proteins albumin and collagen 6A1 as well as αGal epitopes, which seemed to be more sustained. In contrast, in healthy young subjects pre-formed anti-Gal antibodies were reduced by a meat-free nutrition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

International Nuclear Information System (INIS)

Ichikawa, Tomohiro; Sugiura, Hisatoshi; Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki; Ichinose, Masakazu

2013-01-01

Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P 1 production (P 1 release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway

Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

Science.gov (United States)

Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

1984-04-01

Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

Immunohistochemical Distribution of Serum Proteins in Living Mouse Heart with In Vivo Cryotechnique

International Nuclear Information System (INIS)

Shi, Liye; Terada, Nobuo; Saitoh, Yurika; Saitoh, Sei; Ohno, Shinichi

2011-01-01

In vivo cryotechnique (IVCT), which immediately cryofixes target organs in situ, was used to clarify the morphological features of beating heart tissue of living mice. IVCT was performed for diastolic heart tissue under the condition of monitoring with electrocardiogram (ECG). Other mouse hearts were prepared with conventional perfusion-fixation (PF-DH) or immersion-fixation followed by dehydration (IM-DH), and quick-freezing of resected heart tissues (FQF). Immunolocalizations of albumin, immunoglobulin G1 (IgG1), intravenously injected bovine serum albumin (BSA), and connexin 43 were examined after different intervals of BSA injection. In the case of IVCT, the exact stop time of beating mouse hearts was recorded by ECG, and open blood vessels with flowing erythrocytes were observed with less artificial tissue shrinkage than with conventional preparation methods. Both albumin and BSA were well preserved in intercalated discs and t-tubules of cardiomyocytes in addition to blood vessels and interstitial matrices. IgG1 was immunolocalized in interstitial matrices of heart tissues in addition to their blood vessels. At 4 hr after BSA injection, it was immunolocalized in the intercalated discs of cardiomyocytes and lost later at 8 hr. IVCT should prove to be more useful for the morphofunctional examination of dynamically changing heart tissue than conventional preparation methods

Transcapillary transport of metaiodobenzylguanidine (MIBG) in isolated rat heart

International Nuclear Information System (INIS)

DeGrado, Timothy R.; Wang Shuyan

1998-01-01

A better understanding of transcapillary transport for tracer metaiodobenzylguanidine (MIBG) is desirable for development of tracer kinetic models that yield meaningful estimates of neuronal uptake function from tissue radioactivity time courses. This study utilized a multiple-indicator approach in Langendorff-perfused rat hearts to define transport mechanisms and determine the capillary permeability-surface area (PSc) over a broad range of flow (F). Multiple injections within the same heart at different flows allowed characterization of the PSc/F relationship within the same heart. The coefficient of variation of E for multiple injections within the same hearts at constant flow was 6±2% (3 to 6 injections in 9 hearts). In 10 hearts (4 to 6 injections per heart), flow was varied between 2.0-16.5 mL/min. PSc was found to be nearly proportional to flow in each heart (r=0.88±0.14; slope = 0.23±0.10; intercept = 11±7 mL/min/g dry). Tissue hypoxia at low flows, as evidenced by enhanced lactate production, did not appear to influence the PSc/F relationship. Pharmacologic blockade of uptake-1 and uptake-2 had negligible affect on E or PSc as compared with flow-matched controls, although tissue retention was markedly reduced. The results show PSc of MIBG to be nearly proportional to flow but independent of specific neuronal and extraneuronal transport mechanisms and tissue hypoxia. The results are consistent with a passive diffusion process across the capillary endothelial barrier. The increase in PSc with increasing flow could reflect capillary recruitment and/or enhanced capillary permeability

Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology.

Directory of Open Access Journals (Sweden)

Sebastian Schaaf

Full Text Available Human embryonic stem cell (hESC progenies hold great promise as surrogates for human primary cells, particularly if the latter are not available as in the case of cardiomyocytes. However, high content experimental platforms are lacking that allow the function of hESC-derived cardiomyocytes to be studied under relatively physiological and standardized conditions. Here we describe a simple and robust protocol for the generation of fibrin-based human engineered heart tissue (hEHT in a 24-well format using an unselected population of differentiated human embryonic stem cells containing 30-40% α-actinin-positive cardiac myocytes. Human EHTs started to show coherent contractions 5-10 days after casting, reached regular (mean 0.5 Hz and strong (mean 100 µN contractions for up to 8 weeks. They displayed a dense network of longitudinally oriented, interconnected and cross-striated cardiomyocytes. Spontaneous hEHT contractions were analyzed by automated video-optical recording and showed chronotropic responses to calcium and the β-adrenergic agonist isoprenaline. The proarrhythmic compounds E-4031, quinidine, procainamide, cisapride, and sertindole exerted robust, concentration-dependent and reversible decreases in relaxation velocity and irregular beating at concentrations that recapitulate findings in hERG channel assays. In conclusion this study establishes hEHT as a simple in vitro model for heart research.

Automated Texture Analysis and Determination of Fibre Orientation of Heart Tissue: A Morphometric Study.

Science.gov (United States)

Zach, Bernhard; Hofer, Ernst; Asslaber, Martin; Ahammer, Helmut

2016-01-01

The human heart has a heterogeneous structure, which is characterized by different cell types and their spatial configurations. The physical structure, especially the fibre orientation and the interstitial fibrosis, determines the electrical excitation and in further consequence the contractility in macroscopic as well as in microscopic areas. Modern image processing methods and parameters could be used to describe the image content and image texture. In most cases the description of the texture is not satisfying because the fibre orientation, detected with common algorithms, is biased by elements such as fibrocytes or endothelial nuclei. The goal of this work is to figure out if cardiac tissue can be analysed and classified on a microscopic level by automated image processing methods with a focus on an accurate detection of the fibre orientation. Quantitative parameters for identification of textures of different complexity or pathological attributes inside the heart were determined. The focus was set on the detection of the fibre orientation, which was calculated on the basis of the cardiomyocytes' nuclei. It turned out that the orientation of these nuclei corresponded with a high precision to the fibre orientation in the image plane. Additionally, these nuclei also indicated very well the inclination of the fibre.

Acute heart failure

OpenAIRE

Sénior Sánchez, Juan Manuel; Gándara Ricardo, Jairo Alfonso

2015-01-01

We describe the clinical case of a 26 year-old woman who came to Hospital Universitario San Vicente Fundación (Medellín, Colombia) with symptoms and signs of acute heart failure. She had been previously diagnosed with chronic heart failure with reduced ejection fraction without clear origin, pulmonary thromboembolism and ischemic stroke, without optimal neurohormonal modulation. She was admitted with clinical findings of fluid overload and low tissue perfusion, with inotropic support requirem...

Evaluation of heart tissue viability under redox-magnetohydrodynamics conditions: toward fine-tuning flow in biological microfluidics applications.

Science.gov (United States)

Cheah, Lih Tyng; Fritsch, Ingrid; Haswell, Stephen J; Greenman, John

2012-07-01

A microfluidic system containing a chamber for heart tissue biopsies, perfused with Krebs-Henseleit buffer containing glucose and antibiotic (KHGB) using peristaltic pumps and continuously stimulated, was used to evaluate tissue viability under redox-magnetohydrodynamics (redox-MHD) conditions. Redox-MHD possesses unique capabilities to control fluid flow using ionic current from oxidation and reduction processes at electrodes in a magnetic field, making it attractive to fine-tune fluid flow around tissues for "tissue-on-a-chip" applications. The manuscript describes a parallel setup to study two tissue samples simultaneously, and 6-min static incubation with Triton X100. Tissue viability was subsequently determined by assaying perfusate for lactate dehydrogenase (LDH) activity, where LDH serves as an injury marker. Incubation with KHGB containing 5 mM hexaammineruthenium(III) (ruhex) redox species with and without a pair of NdFeB magnets (∼ 0.39 T, placed parallel to the chamber) exhibited no additional tissue insult. MHD fluid flow, viewed by tracking microbeads with microscopy, occurred only when the magnet was present and stimulating electrodes were activated. Pulsating MHD flow with a frequency similar to the stimulating waveform was superimposed over thermal convection (from a hotplate) for Triton-KHGB, but fluid speed was up to twice as fast for ruhex-Triton-KHGB. A large transient ionic current, achieved when switching on the stimulating electrodes, generates MHD perturbations visible over varying peristaltic flow. The well-controlled flow methodology of redox-MHD is applicable to any tissue type, being useful in various drug uptake and toxicity studies, and can be combined equally with on- or off-device analysis modalities. Copyright © 2012 Wiley Periodicals, Inc.

Carbon monoxide and coronary heart disease

Energy Technology Data Exchange (ETDEWEB)

Scheidemandel, V

1974-01-01

Studies on the relationship between increased carboxyhemoglobin levels in the blood and coronary heart disease in smokers and city dwellers are reviewed. The evidence of myocardial infarction is significantly higher in smokers than in nonsmokers which is due, apart from nicotine which promotes coronary arteriosclerosis, to inhaled carbon monoxide which leads to increased carboxyhemoglobin levels and most likely plays a role in the risk of arteriosclerosis and the coronary heart disease. Apart from combining with hemoglobin, CO increases the circulation rate and the coronary blood flow, and reduces the coronary arteriovenous oxygen difference, which is indicative of a reduced rate of oxygen extraction by the myocardium against an increased myocardial oxygen demand. The reduction of the oxygen extraction correlates with the increased COHb level. Inhaled CO lowers the threshold of angina pectoris due to the reduced myocardial oxygen tension. Also, considerable reduction of the oxygen diffusion from the capillaries toward the mitochondria due to the combination of CO with myoglobin is observed. Chronically increased CO levels in the blood and tissues not only accelerate the development of arteriosclerosis, but also induce a process directly injurious to the myocardial metabolism. (Air Pollut. Abstr.)

Core Promoter Plasticity Between Maize Tissues and Genotypes Contrasts with Predominance of Sharp Transcription Initiation Sites.

Science.gov (United States)

Mejía-Guerra, María Katherine; Li, Wei; Galeano, Narmer F; Vidal, Mabel; Gray, John; Doseff, Andrea I; Grotewold, Erich

2015-12-01

Core promoters are crucial for gene regulation, providing blueprints for the assembly of transcriptional machinery at transcription start sites (TSSs). Empirically, TSSs define the coordinates of core promoters and other regulatory sequences. Thus, experimental TSS identification provides an essential step in the characterization of promoters and their features. Here, we describe the application of CAGE (cap analysis of gene expression) to identify genome-wide TSSs used in root and shoot tissues of two maize (Zea mays) inbred lines (B73 and Mo17). Our studies indicate that most TSS clusters are sharp in maize, similar to mice, but distinct from Arabidopsis thaliana, Drosophila melanogaster, or zebra fish, in which a majority of genes have broad-shaped TSS clusters. We established that ∼38% of maize promoters are characterized by a broader TATA-motif consensus, and this motif is significantly enriched in genes with sharp TSSs. A noteworthy plasticity in TSS usage between tissues and inbreds was uncovered, with ∼1500 genes showing significantly different dominant TSSs, sometimes affecting protein sequence by providing alternate translation initiation codons. We experimentally characterized instances in which this differential TSS utilization results in protein isoforms with additional domains or targeted to distinct subcellular compartments. These results provide important insights into TSS selection and gene expression in an agronomically important crop. © 2015 American Society of Plant Biologists. All rights reserved.

The effects of the sulfonylurea glyburide on glutathione peroxidase, superoxide dismutase and catalase activities in the heart tissue of streptozotocin-induced diabetic rat.

Science.gov (United States)

Bukan, N; Sancak, B; Bilgihan, A; Kosova, F; Buğdayci, G; Altan, N

2004-09-01

Oxygen free radicals have been suggested to be a contributory factor in diabetes complications. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the heart tissue of diabetic rats. We investigated the activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in the hearts of both control and streptozotocin-induced diabetic rats. In the heart of diabetic rats, the activity of total superoxide dismutase decreased significantly (p < 0.005), whereas the activity of catalase and glutathione peroxidase increased to a large extent (p < 0.0001 and p = 0.05, respectively) at the end of the fourth week compared with the control group. Glyburide treatment of diabetic rats for 4 weeks corrected the changes observed in diabetic heart. In addition, blood glucose levels of untreated diabetic rats decreased following the glyburide treatment. These results demonstrate that the sulfonylurea glyburide is capable of exerting direct insulin-like effect on heart superoxide dismutase, catalase and glutathione peroxidase activities of diabetic rats in vivo.

The effects of electromagnetic radiation (2450 MHz wireless devices) on the heart and blood tissue: role of melatonin.

Science.gov (United States)

Gumral, N; Saygin, M; Asci, H; Uguz, A C; Celik, O; Doguc, D K; Savas, H B; Comlekci, S

2016-01-01

This study was designed to investigate the effects of 2450 MHz EMR on the heart and blood in rat and possible ameliorating effects of melatonin. Thirty-two female Wistar Albino rats were randomly grouped (by eight in each group) as follows:  Group I: cage-control group (dimethysulfoxide (DMSO), 10mg/kg/day i.p. without stress and EMR. Group II: sham-control rats stayed in restrainer without EMR and DMSO (10mg/kg/day i.p.). Group III: rats exposed to 2450 MHz EMR. Group IV: treated group rats exposed to 2450 MHz EMR+melatonin (MLT) (10mg/kg/day i.p.). In the blood tissue, there was no significant difference between the groups in respect of erythrocytes GSH, GSH-Px activity, plasma LP level and vitamin A concentration (p > 0.05). However, in the Group IV, erythrocytes' LP levels (p < 0.05) were observed to be significantly decreased while plasma vitamin C, and vitamin E concentrations (p < 0.05) were found to be increased when compared to Group III. In the heart tissues, MDA and NO levels significantly increased in group III compared with groups I and II (p < 0.05). Contrary to these oxidant levels, CAT and SOD enzyme activities decreased significantly in group III compared with groups I and II (p 0.05). Besides, MLT treatment lowered the MDA and NO levels compared with group III. In conclusion, these results demonstrated that contrary to its effect on the heart, the wireless (2450 MHz) devices cause slight oxidative-antioxidative changes in the blood of rats, and a moderate melatonin supplementation may play an important role in the antioxidant system (plasma vitamin C and vitamin E). However, further investigations are required to clarify the mechanism of action of the applied 2450 MHz EMR exposure (Tab. 3, Fig. 1, Ref. 49).

Concentration of 17 Elements in Subcellular Fractions of Beef Heart Tissue Determined by Neutron Activation Analysis

Energy Technology Data Exchange (ETDEWEB)

Wester, P O

1964-12-15

Subcellular fractions of beef heart tissue are investigated, by means of neutron activation analysis, with respect to their concentration of 17 different elements. A recently developed ion-exchange technique combined with gamma spectrometry is used. The homogeneity of the subcellular fractions is examined electron microscopically. The following elements are determined: As, Ba, Br, Cas Co, Cs, Cu, Fe, Hg, La, Mo, P, Rb, Se, Sm, W and Zn. The determination of Ag, Au, Cd, Ce, Cr, Sb and Sc is omitted, in view of contamination. Reproducible and characteristic patterns of distribution are obtained for all elements studied.

Concentration of 17 Elements in Subcellular Fractions of Beef Heart Tissue Determined by Neutron Activation Analysis

International Nuclear Information System (INIS)

Wester, P.O.

1964-12-01

Subcellular fractions of beef heart tissue are investigated, by means of neutron activation analysis, with respect to their concentration of 17 different elements. A recently developed ion-exchange technique combined with gamma spectrometry is used. The homogeneity of the subcellular fractions is examined electron microscopically. The following elements are determined: As, Ba, Br, Cas Co, Cs, Cu, Fe, Hg, La, Mo, P, Rb, Se, Sm, W and Zn. The determination of Ag, Au, Cd, Ce, Cr, Sb and Sc is omitted, in view of contamination. Reproducible and characteristic patterns of distribution are obtained for all elements studied

Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

Science.gov (United States)

Chausse, Bruno; Vieira-Lara, Marcel A; Sanchez, Angélica B; Medeiros, Marisa H G; Kowaltowski, Alicia J

2015-01-01

Intermittent fasting (IF) is a dietary intervention often used as an alternative to caloric restriction (CR) and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

Intermittent fasting results in tissue-specific changes in bioenergetics and redox state.

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Bruno Chausse

Full Text Available Intermittent fasting (IF is a dietary intervention often used as an alternative to caloric restriction (CR and characterized by 24 hour cycles alternating ad libitum feeding and fasting. Although the consequences of CR are well studied, the effects of IF on redox status are not. Here, we address the effects of IF on redox state markers in different tissues in order to uncover how changes in feeding frequency alter redox balance in rats. IF rats displayed lower body mass due to decreased energy conversion efficiency. Livers in IF rats presented increased mitochondrial respiratory capacity and enhanced levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain that was not related to changes in mitochondrial bioenergetics. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in mitochondrial bioenergetics or redox homeostasis was observed in skeletal muscles of IF animals. Overall, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain and protection against oxidative damage in the heart.

Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts

Czech Academy of Sciences Publication Activity Database

Kolesová, H.; Čapek, Martin; Radochová, Barbora; Janáček, Jiří; Sedmera, David

2016-01-01

Roč. 146, č. 2 (2016), s. 142-152 ISSN 0948-6143 R&D Projects: GA ČR(CZ) GA13-12412S; GA MŠk(CZ) LH13028 Institutional support: RVO:67985823 Keywords : green fluorescent protein (GFP) * confocal microscopy * optical projection tomography * tissue transparency * heart * embryo Subject RIV: EA - Cell Biology Impact factor: 2.553, year: 2016

Qualitative evaluation of Chang method of attenuation correction on heart SPECT by using custom made heart phantom

International Nuclear Information System (INIS)

Takavar, A.; Eftekhari, M.; Beiki, D.; Saghari, M.; Mostaghim, N.; Sohrabi, M.

2003-01-01

SPECT detects γ- rays from administrated radiopharmaceutical within the patient body. γ-rays pass through different tissues before reaching detectors and are attenuated. Attenuation can cause artifacts; therefore different and used to minimize attenuation effects. In our study efficacy of Chang method was evaluated for attenuation purpose, using a custom made heart phantom. Due to different tissues surrounding heart, evaluation is not uniform more over activity distribution around heart is also non- uniform. In Chang method distribution of radioactivity and attenuation due to the surrounding tissue is considered uniform. Our phantom is a piece of plastic producing similar SPECT image as left ventricle. A dual head, ADAC system was used in our study. Images were taken by 180 d ig C (limited angle) and 360 d ig C (total rotation). Images are compared with and without attenuation correction. Our results indicate that Chang attenuation correction method is not capable of eliminating attenuation artifact completely in particular attenuation effects caused by breast

(S)Partners for Heart Health: a school-based program for enhancing physical activity and nutrition to promote cardiovascular health in 5th grade students

OpenAIRE

Carlson, Joseph J; Eisenmann, Joey C; Pfeiffer, Karin A; Jager, Kathleen B; Sehnert, Scott T; Yee, Kimbo E; Klavinski, Rita A; Feltz, Deborah L

2008-01-01

Abstract Background The American Heart Association Position Statement on Cardiovascular Health Promotion in Public Schools encourages school-based interventions for the primary prevention of cardiovascular disease (CVD) through risk factor prevention or reduction in children with an emphasis on creating an environment that promotes healthy food choices and physical activity (PA). In an effort to address issues related to CVD risk factors including obesity in Michigan children, a multi-discipl...

No adaptation to digitalization as evaluated by digitalis receptor (Na,K-ATPase) quantification in explanted hearts from donors without heart disease and from digitalized recipients with end-stage heart failure.

Science.gov (United States)

Schmidt, T A; Allen, P D; Colucci, W S; Marsh, J D; Kjeldsen, K

1993-01-01

Speculations about development of tolerance to the inotropic effect of digitalis have been engendered since studies in various in vitro systems and tissues not representative of the heart have shown up-regulation of sodium potassium adenosine triphosphatase (Na,K-ATPase) when exposed to digitalis. Moreover the digitalis receptor (i.e., Na,K-ATPase) concentration in the normal, vital human left ventricle has not been previously determined. On this basis, digitalis receptor concentration was quantified in the left ventricle of explanted hearts from subjects without heart disease and from patients with end-stage heart failure who had received digitalis therapy. This was performed using vanadate-facilitated 3H-ouabain binding to intact tissue samples giving values of 728 +/- 58 (n = 5) and 467 +/- 55 pmol/g wet weight (n = 6) (mean +/- SEM) (p digitalization was associated with occupancy of digitalis receptors in the failing human heart of 24% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo

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Marietta Herrmann

2014-11-01

We demonstrate that this population of cells, isolated in a clinically relevant manner and cultured with autologous growth factors readily promoted neovascularization in tissue engineered constructs in vivo enabling a potential translation into the clinic.

Visualization of human heart conduction system by means of fluorescence spectroscopy

Science.gov (United States)

Venius, Jonas; Bagdonas, Saulius; Žurauskas, Edvardas; Rotomskis, Ricardas

2011-10-01

The conduction system of the heart is a specific muscular tissue, where a heartbeat signal originates and initiates the depolarization of the ventricles. The muscular origin makes it complicated to distinguish the conduction system from the surrounding tissues. A surgical intervention can lead to the accidental harm of the conduction system, which may eventually result in a dangerous obstruction of the heart functionality. Therefore, there is an immense necessity for developing a helpful method to visualize the conduction system during the operation time. The specimens for the spectroscopic studies were taken from nine diverse human hearts. The localization of distinct types of the tissue was preliminary marked by the pathologist and approved histologically after the spectral measurements. Variations in intensity, as well as in shape, were detected in autofluorescence spectra of different heart tissues. The most distinct differences were observed between the heart conduction system and the surrounding tissues under 330 and 380 nm excitation. The spectral region around 460 nm appeared to be the most suitable for an unambiguous differentiation of the human conduction system avoiding the absorption peak of blood. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, was also demonstrated.

HISTOPATHOLOGICAL EFFECTS OF (4S)-2-(4-HYDROXY-3-METHOXYPHENYL) THIAZOLIDINE-4-CARBOXYLIC ACID ON ZEBRAFISH (Danio rerio) HEART TISSUE

OpenAIRE

YÖN, Nazan Deniz; ÖZTÜRK, Burcu; ZENGİN, Mustafa; AKBULUT, Cansu

2018-01-01

Examination thehistopathological effects of (4s)-2-(4-hydroxy-3-methoxyphenyl) thiazolidine-4-carboxylicacid on heart tissue of zebrafish were aimed.Introduction:(4S)-2-(4-hydroxy-3-methoxyphenyl) thiazolidine-4-carboxylic acid is newsynthesized substance which obtained from cysteine and valine. Because ofthiazolidine derivates have important biological responses scientist workintensively on these compounds recent years. It is obvious that thiazolidinecontained compounds will be used in futur...

[sup 123]I-iodobenzoylglucosamines: glucose analogues for heart imaging

Energy Technology Data Exchange (ETDEWEB)

Lutz, T [British Columbia Univ., Vancouver, BC (Canada). Dept. of Pharmaceutical Sciences; Dougan, H [TRIUMF, Vancouver, BC (Canada); Rihela, T; Vo, C V [Vancouver General Hospital (Canada). Div. of Nuclear Medicine; Lyster, D M [British Columbia Univ., Vancouver, BC (Canada). Dept. of Pharmaceutical Sciences Vancouver General Hospital (Canada). Div. of Nuclear Medicine

1993-01-01

The ortho-, meta- and para-[[sup 123]I]-2-deoxy-2-N-(iodobenzoyl)-D-glucosamine (BGA) derivatives were investigated to determine the effect of iodine position and lipophilicity on tissue distribution. There was no correlation between tissue uptake and lipophilicity. Maximum uptake was observed for o-BGA displaying a heart:blood ratio of 36.0 at 18 hours post injection. Yeast hexokinase phosphorylation studies in vitro and an in vivo insulin experiment were carried out on o-BGA. No phosphorylation was detected, but the insulin study indicated that o-BGA uses the glucose transporter. o-BGA showed maximum tissue uptake in mice at an optimal specific activity of 0.004mg/[mu]Ci. Mouse biodistribution studies of o-[[sup 123]I]-iodobenzamide(o-[sup 123]IBA) indicated that the glucose moiety of o-BGA may be involved in the heart accumulation process in mice. Heart tissue extraction studies showed unmetabolized o-[[sup 123]I]BGA was the predominant species. A rabbit image of o-[[sup 123]I]BGA, recorded at 14 hours post injection, showed significant heart uptake. (author).

Acute effects of nandrolone decanoate on oxidative stress in isolated rat heart

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Jevđević Maja

2015-01-01

Full Text Available Abuse of anabolic-androgenic steroids (AAS produces side effects in different tissues, with oxidative stress linked to their pathophysiology, being involved in fibrosis, cellular proliferation, and tumorigenesis. The aim of this study was to examine the acute effects of nandrolone decanoate (ND on oxidative stress in isolated rat heart. The hearts of male Wistar albino were excised and perfused according to the Langendorff technique at gradually increasing coronary perfusion pressures (40-120 cmH2O. The hearts were perfused with ND at doses of 1, 10 and 100 μM. Oxidative stress markers, including the index of lipid peroxidation (thiobarbituric acid reactive substances (TBARS, nitric oxide (nitrites; NO2-, the superoxide anion radical (O2- and hydrogen peroxide (H2O2 were measured in the coronary venous effluent. Our results showed that acute effects of ND do not promote the production of reactive oxygen species (ROS. Our finding pointed out that the highest concentration of ND may even possess some anti-oxidative potential, which should be examined further.

Alternative promoter usage of the membrane glycoprotein CD36

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Whatling Carl

2006-03-01

Full Text Available Abstract Background CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation. Results We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters. Conclusion Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering

OpenAIRE

Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

2010-01-01

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-s...

[Evaluation of heart impact in the 100 m extreme intensity sport using near-infrared non-invasive muscle oxygen detecting device and sports heart rate detection technology].

Science.gov (United States)

Wang, Pei-Yong; Long, Fei-Xiao; Fu, Lan-Ying; Li, Yue; Ding, Hai-Shu; Qu, An-Lian; Zhou, Xiao-Ping

2010-02-01

Using continuous two wavelength near-infrared technology to detect the variation in the consistency of oxygen hemoglobin in the muscle and the sports heart rate wireless real time collection technology, we devised the real time muscle tissue oxygenation and instantaneous heart rate experiment scheme and implemented it for the process of the 100 m run with two parameters given simultaneously. The experiment shows that the concentration of the oxygen hemoglobin in the muscle tissue continues decreasing after the end of the 100 m run, and the time interval between the moment when the concentration of the oxygen hemoglobin attains the minimum value and the moment when the athletes finish the 100 m run is (6.65 +/- 1.10) sec; while the heart rate continues increasing after the end of the 100 m run, and the time interval between the moment when the heart rate attains the maximum value and the moment when the athletes finish the 100 m run is (8.00 +/- 1.57) sec. The results show that the two wavelength near-infrared tissue oxygenation detection technology and the sports heart rate real time collection equipment can accurately measure the sports tissue oxygenation and the heart rate in the extreme intensity sport, and reveal the process of muscle oxygen transportation and consumption and its dynamic character with the heart rate in the extreme intensity sport.

Growth and remodeling play opposing roles during postnatal human heart valve development.

Science.gov (United States)

Oomen, Pim J A; Holland, Maria A; Bouten, Carlijn V C; Kuhl, Ellen; Loerakker, Sandra

2018-01-19

Tissue growth and remodeling are known to govern mechanical homeostasis in biological tissue, but their relative contributions to homeostasis remain unclear. Here, we use mechanical models, fueled by experimental findings, to demonstrate that growth and remodeling have different effects on heart valve stretch homeostasis during physiological postnatal development. Two developmental stages were considered: early-stage (from infant to adolescent) and late-stage (from adolescent to adult) development. Our models indicated that growth and remodeling play opposing roles in preserving tissue stretch and with time. During early-stage development, excessive tissue stretch was decreased by tissue growth and increased by remodeling. In contrast, during late-stage development tissue stretch was decreased by remodeling and increased by growth. Our findings contribute to an improved understanding of native heart valve adaptation throughout life, and are highly relevant for the development of tissue-engineered heart valves.

Cardiac-Specific Gene Expression Facilitated by an Enhanced Myosin Light Chain Promoter

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Wolfgang Boecker

2004-04-01

Full Text Available Background: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. Methods: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc reporter gene (Ad.4 × MLC250.Luc. Rat cardiomyocytes, liver and kidney cells were infected with Ad.4 × MLC.Luc or control vectors. For in vivo testing, Ad.4 × MLC250.Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. Results: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells was 20.4 versus 0.9 (Ad.4 × MLC250.Luc vs. Ad.CMV. In vivo: Ad.4 × MLC250.Luc significantly reduced luc activity in liver (38.4-fold, lung (16.1-fold, and kidney (21.8-fold versus Ad.CMV (p = .01; whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad.4 × MLC.Luc versus 1:1.4 (Ad.CMV.Luc. Discussion: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart.

The Somatic Reproductive Tissues of C. elegans Promote Longevity through Steroid Hormone Signaling

Science.gov (United States)

Yamawaki, Tracy M.; Berman, Jennifer R.; Suchanek-Kavipurapu, Monika; McCormick, Mark; Gaglia, Marta Maria; Lee, Seung-Jae; Kenyon, Cynthia

2010-01-01

In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12. PMID:20824162

The somatic reproductive tissues of C. elegans promote longevity through steroid hormone signaling.

Directory of Open Access Journals (Sweden)

Tracy M Yamawaki

2010-08-01

Full Text Available In Caenorhabditis elegans and Drosophila melanogaster, removing the germline precursor cells increases lifespan. In worms, and possibly also in flies, this lifespan extension requires the presence of somatic reproductive tissues. How the somatic gonad signals other tissues to increase lifespan is not known. The lifespan increase triggered by loss of the germ cells is known to require sterol hormone signaling, as reducing the activity of the nuclear hormone receptor DAF-12, or genes required for synthesis of the DAF-12 ligand dafachronic acid, prevents germline loss from extending lifespan. In addition to sterol signaling, the FOXO transcription factor DAF-16 is required to extend lifespan in animals that lack germ cells. DAF-12/NHR is known to assist with the nuclear accumulation of DAF-16/FOXO in these animals, yet we find that loss of DAF-12/NHR has little or no effect on the expression of at least some DAF-16/FOXO target genes. In this study, we show that the DAF-12-sterol signaling pathway has a second function to activate a distinct set of genes and extend lifespan in response to the somatic reproductive tissues. When germline-deficient animals lacking somatic reproductive tissues are given dafachronic acid, their expression of DAF-12/NHR-dependent target genes is restored and their lifespan is increased. Together, our findings indicate that in C. elegans lacking germ cells, the somatic reproductive tissues promote longevity via steroid hormone signaling to DAF-12.

Advances in tissue engineering through stem cell-based co-culture.

Science.gov (United States)

Paschos, Nikolaos K; Brown, Wendy E; Eswaramoorthy, Rajalakshmanan; Hu, Jerry C; Athanasiou, Kyriacos A

2015-05-01

Stem cells are the future in tissue engineering and regeneration. In a co-culture, stem cells not only provide a target cell source with multipotent differentiation capacity, but can also act as assisting cells that promote tissue homeostasis, metabolism, growth and repair. Their incorporation into co-culture systems seems to be important in the creation of complex tissues or organs. In this review, critical aspects of stem cell use in co-culture systems are discussed. Direct and indirect co-culture methodologies used in tissue engineering are described, along with various characteristics of cellular interactions in these systems. Direct cell-cell contact, cell-extracellular matrix interaction and signalling via soluble factors are presented. The advantages of stem cell co-culture strategies and their applications in tissue engineering and regenerative medicine are portrayed through specific examples for several tissues, including orthopaedic soft tissues, bone, heart, vasculature, lung, kidney, liver and nerve. A concise review of the progress and the lessons learned are provided, with a focus on recent developments and their implications. It is hoped that knowledge developed from one tissue can be translated to other tissues. Finally, we address challenges in tissue engineering and regenerative medicine that can potentially be overcome via employing strategies for stem cell co-culture use. Copyright © 2014 John Wiley & Sons, Ltd.

Effectiveness of a Walking Group Intervention to Promote Physical Activity and Cardiovascular Health in Predominantly Non-Hispanic Black and Hispanic Urban Neighborhoods: Findings from the Walk Your Heart to Health Intervention

Science.gov (United States)

Schulz, Amy J.; Israel, Barbara A.; Mentz, Graciela B.; Bernal, Cristina; Caver, Deanna; DeMajo, Ricardo; Diaz, Gregoria; Gamboa, Cindy; Gaines, Causandra; Hoston, Bernadine; Opperman, Alisha; Reyes, Angela G.; Rowe, Zachary; Sand, Sharon L.; Woods, Sachiko

2015-01-01

Objectives: The purpose of this study was to evaluate the effectiveness of the "Walk Your Heart to Health" ("WYHH") intervention, one component of the multilevel Community Approaches to Cardiovascular Health: Pathways to Heart Health (CATCH:PATH) intervention designed to promote physical activity and reduce cardiovascular risk…

Tissue Banking: Current procedures, ethical consideration and ...

African Journals Online (AJOL)

Tissue banking provides safe and effective cells and tissues for transplantation in reconstruction surgery. Bone, amnion, skin, cartilage, heart valves and xenograft tissues are the most commonly used biological tissues. Acquisition of tissue is dependent on elaborate donor screening criteria based on medical and social ...

Human engineered heart tissue as a model system for drug testing.

Science.gov (United States)

Eder, Alexandra; Vollert, Ingra; Hansen, Arne; Eschenhagen, Thomas

2016-01-15

Drug development is time- and cost-intensive and, despite extensive efforts, still hampered by the limited value of current preclinical test systems to predict side effects, including proarrhythmic and cardiotoxic effects in clinical practice. Part of the problem may be related to species-dependent differences in cardiomyocyte biology. Therefore, the event of readily available human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CM) has raised hopes that this human test bed could improve preclinical safety pharmacology as well as drug discovery approaches. However, hiPSC-CM are immature and exhibit peculiarities in terms of ion channel function, gene expression, structural organization and functional responses to drugs that limit their present usefulness. Current efforts are thus directed towards improving hiPSC-CM maturity and high-content readouts. Culturing hiPSC-CM as 3-dimensional engineered heart tissue (EHT) improves CM maturity and anisotropy and, in a 24-well format using silicone racks, enables automated, multiplexed high content readout of contractile function. This review summarizes the principal technology and focuses on advantages and disadvantages of this technology and its potential for preclinical drug screening. Copyright © 2015 Elsevier B.V. All rights reserved.

DNA methylation abnormalities in congenital heart disease.

Science.gov (United States)

Serra-Juhé, Clara; Cuscó, Ivon; Homs, Aïda; Flores, Raquel; Torán, Núria; Pérez-Jurado, Luis A

2015-01-01

Congenital heart defects represent the most common malformation at birth, occurring also in ∼50% of individuals with Down syndrome. Congenital heart defects are thought to have multifactorial etiology, but the main causes are largely unknown. We have explored the global methylation profile of fetal heart DNA in comparison to blood DNA from control subjects: an absolute correlation with the type of tissue was detected. Pathway analysis revealed a significant enrichment of differential methylation at genes related to muscle contraction and cardiomyopathies in the developing heart DNA. We have also searched for abnormal methylation profiles on developing heart-tissue DNA of syndromic and non-syndromic congenital heart defects. On average, 3 regions with aberrant methylation were detected per sample and 18 regions were found differentially methylated between groups. Several epimutations were detected in candidate genes involved in growth regulation, apoptosis and folate pathway. A likely pathogenic hypermethylation of several intragenic sites at the MSX1 gene, involved in outflow tract morphogenesis, was found in a fetus with isolated heart malformation. In addition, hypermethylation of the GATA4 gene was present in fetuses with Down syndrome with or without congenital heart defects, as well as in fetuses with isolated heart malformations. Expression deregulation of the abnormally methylated genes was detected. Our data indicate that epigenetic alterations of relevant genes are present in developing heart DNA in fetuses with both isolated and syndromic heart malformations. These epimutations likely contribute to the pathogenesis of the malformation by cis-acting effects on gene expression.

Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

International Nuclear Information System (INIS)

Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

2013-01-01

To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

Energy Technology Data Exchange (ETDEWEB)

Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

2013-09-27

To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

Tissue specific promoters improve the localization of radiation-inducible gene expression

International Nuclear Information System (INIS)

Hallahan, Dennis; Kataoka, Yasushi; Kuchibhotla, Jaya; Virudachalam, Subbu; Weichselbaum, Ralph

1996-01-01

expression was quantified in vascular endothelial cells from large vessel (HUVEC) and small vessels (HMEC). We found cell-type specificity of radiation-induction. The promoter region from the ELAM gene gave no expression in cells that were not of endothelial cell origin and x-ray-induction of ELAM in the endothelium required the NFkB binding cis-acting element. ELAM induction was achieved at doses as low as 1 Gy, whereas induction of other radiation inducible genes required 5 to 10 Gy. Cells transfected with the minimal promoter (plasmid pTK-CAT) demonstrated no radiation induction. Expression of the CMV-LacZ genetic construct that was used as a negative control in each transfection was not altered by x-irradiation. Moreover, intravenous administration of liposomes containing a reporter gene linked to the ELAM promoter and a transcriptional amplification system were induced specifically at sites of x-irradiation in an animal model. Conclusions: Activation of transcription of the ELAM-1 promoter by ionizing radiation is a means of activating gene therapy within the vascular endothelium and demonstrates the feasibility of treating vascular lesions with noninvasive procedures. Tissue specific promoters (e. g., ELAM-1) combined with radiation inducible gene therapy improves the localization of gene therapy expression. These results have applications in intravascular brachytherapy for the prevention of blood vessel restenosis

Cardiac tissue engineering

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MILICA RADISIC

2005-03-01

Full Text Available We hypothesized that clinically sized (1-5 mm thick,compact cardiac constructs containing physiologically high density of viable cells (~108 cells/cm3 can be engineered in vitro by using biomimetic culture systems capable of providing oxygen transport and electrical stimulation, designed to mimic those in native heart. This hypothesis was tested by culturing rat heart cells on polymer scaffolds, either with perfusion of culture medium (physiologic interstitial velocity, supplementation of perfluorocarbons, or with electrical stimulation (continuous application of biphasic pulses, 2 ms, 5 V, 1 Hz. Tissue constructs cultured without perfusion or electrical stimulation served as controls. Medium perfusion and addition of perfluorocarbons resulted in compact, thick constructs containing physiologic density of viable, electromechanically coupled cells, in contrast to control constructs which had only a ~100 mm thick peripheral region with functionally connected cells. Electrical stimulation of cultured constructs resulted in markedly improved contractile properties, increased amounts of cardiac proteins, and remarkably well developed ultrastructure (similar to that of native heart as compared to non-stimulated controls. We discuss here the state of the art of cardiac tissue engineering, in light of the biomimetic approach that reproduces in vitro some of the conditions present during normal tissue development.

In vivo biocompatibility of porous silicon biomaterials for drug delivery to the heart.

Science.gov (United States)

Tölli, Marja A; Ferreira, Mónica P A; Kinnunen, Sini M; Rysä, Jaana; Mäkilä, Ermei M; Szabó, Zoltán; Serpi, Raisa E; Ohukainen, Pauli J; Välimäki, Mika J; Correia, Alexandra M R; Salonen, Jarno J; Hirvonen, Jouni T; Ruskoaho, Heikki J; Santos, Hélder A

2014-09-01

Myocardial infarction (MI), commonly known as a heart attack, is the irreversible necrosis of heart muscle secondary to prolonged ischemia, which is an increasing problem in terms of morbidity, mortality and healthcare costs worldwide. Along with the idea to develop nanocarriers that efficiently deliver therapeutic agents to target the heart, in this study, we aimed to test the in vivo biocompatibility of different sizes of thermally hydrocarbonized porous silicon (THCPSi) microparticles and thermally oxidized porous silicon (TOPSi) micro and nanoparticles in the heart tissue. Despite the absence or low cytotoxicity, both particle types showed good in vivo biocompatibility, with no influence on hematological parameters and no considerable changes in cardiac function before and after MI. The local injection of THCPSi microparticles into the myocardium led to significant higher activation of inflammatory cytokine and fibrosis promoting genes compared to TOPSi micro and nanoparticles; however, both particles showed no significant effect on myocardial fibrosis at one week post-injection. Our results suggest that THCPSi and TOPSi micro and nanoparticles could be applied for cardiac delivery of therapeutic agents in the future, and the PSi biomaterials might serve as a promising platform for the specific treatment of heart diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Interaction between Obesity and the NFKB1 - 94ins/delATTG Promoter Polymorphism in Relation to Incident Acute Coronary Syndrome

DEFF Research Database (Denmark)

Stegger, Jakob Gerhard; Schmidt, Erik Berg; Berentzen, Tina Landsvig

2013-01-01

The NF-κB transcription factor family regulates several genes encoding pro-inflammatory and anti-inflammatory proteins in adipose tissues and in atherosclerotic plaques. The deletion variant allele of the NFKB1 - 94ins/delATTG promoter polymorphism leads to lower transcript levels of the p50...... subunit, and the variant allele has been associated with the risk of several inflammatory diseases as well as coronary heart disease where inflammation is important in the pathogenesis. The objective of this study was to explore the potential interaction between the NFKB1-94ins/delATTG promoter...

Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

Science.gov (United States)

Hasan, Wohaib; Smith, Peter G

2014-04-01

Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves. Copyright © 2013 Elsevier B.V. All rights reserved.

Ruminant and industrial trans-fatty acid uptake in the heart.

Science.gov (United States)

Ganguly, Riya; LaVallee, Renee; Maddaford, Thane G; Devaney, Brittany; Bassett, Chantal M C; Edel, Andrea L; Pierce, Grant N

2016-05-01

Dietary trans-fats are strongly associated with heart disease. However, the capacity for the tissues of the body, and specifically the heart, to take up trans-fats is unknown. It is also unknown if different trans-fats have different uptake capacities in the heart and other tissues of the body. Diets of low-density lipoprotein receptor-deficient mice were supplemented for 14weeks with foods that contained 1.5% of the trans-fat elaidic acid or vaccenic acid. Tissues were extracted and frozen in liquid nitrogen, and then lipids were analyzed by gas chromatography for fatty acid content. Isolated cardiomyocytes were also exposed to elaidic or vaccenic acid in cell culture media for 24h. Dietary supplementation with vaccenic or elaidic acid resulted in a 20-fold higher accumulation of these TFAs in fat deposits in the body in comparison to liver. Liver tissue accumulated about twice as much per gram tissue as heart. Similar quantities of both elaidic acid and vaccenic acid were taken up by the tissues. Isolated cardiomyocytes exhibited an unusually large uptake of trans-fat, and this was dependent upon both the concentration and duration of exposure to the trans-fats but not upon the type of trans-fat. Expression levels of CD36 and FATP4 were not significantly changed during dietary interventions or exposure of cells to trans-fats. We conclude that fat, liver and heart (including cardiomyocytes) are all capable of accumulating trans-fat in response to dietary supplementation without changes in fatty acid transport protein expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Deletion analysis of susy-sl promoter for the identification of optimal promoter sequence

International Nuclear Information System (INIS)

Bacha, S.; Khatoon, A.; Asif, M.; Bshir, A.

2015-01-01

The promoter region of sucrose synthase (susy-Sl) was identified and isolated from tomato. The 5? deletion analysis was carried out for the identification of minimum optimal promoter. Transgenic lines of Arabidopsis thaliana were developed by floral dip method incorporating various promoter deletion cassettes controlling GUS reporter gene. GUS assay of transgenic tissues indicated that full length susy-Sl promoter and its deletion mutants were constitutively expressed in vegetative and floral tissues of A. thaliana. The expression was observed in roots, shoots and flowers of A. thaliana. Analysis of 5? deletion series of susy-Sl promoter showed that a minimum of 679 bp fragment of the promoter was sufficient to drive expression of GUS reporter gene in the major tissues of transgenic A. thaliana. (author)

Is Graphene a Promising Nano-Material for Promoting Surface Modification of Implants or Scaffold Materials in Bone Tissue Engineering?

Science.gov (United States)

Gu, Ming; Liu, Yunsong; Chen, Tong; Du, Feng; Zhao, Xianghui; Xiong, Chunyang

2014-01-01

Bone tissue engineering promises to restore bone defects that are caused by severe trauma, congenital malformations, tumors, and nonunion fractures. How to effectively promote the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field. Many researchers are studying the ways of conferring a pro-osteodifferentiation or osteoinductive capability on implants or scaffold materials, where osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of coating material that may confer the pro-osteodifferentiation capability on implants and scaffold materials by surface modification. Here, we review recent studies on the effects of graphene on surface modifications of implants or scaffold materials. The ability of graphene to improve the mechanical and biological properties of implants or scaffold materials, such as nitinol and carbon nanotubes, and its ability to promote the adhesion, proliferation, and osteogenic differentiation of MSCs or osteoblasts have been demonstrated in several studies. Most previous studies were performed in vitro, but further studies will explore the mechanisms of graphene's effects on bone regeneration, its in vivo biocompatibility, its ability to promote osteodifferentiation, and its potential applications in bone tissue engineering. PMID:24447041

Is graphene a promising nano-material for promoting surface modification of implants or scaffold materials in bone tissue engineering?

Science.gov (United States)

Gu, Ming; Liu, Yunsong; Chen, Tong; Du, Feng; Zhao, Xianghui; Xiong, Chunyang; Zhou, Yongsheng

2014-10-01

Bone tissue engineering promises to restore bone defects that are caused by severe trauma, congenital malformations, tumors, and nonunion fractures. How to effectively promote the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) or seed cells has become a hot topic in this field. Many researchers are studying the ways of conferring a pro-osteodifferentiation or osteoinductive capability on implants or scaffold materials, where osteogenesis of seed cells is promoted. Graphene (G) provides a new kind of coating material that may confer the pro-osteodifferentiation capability on implants and scaffold materials by surface modification. Here, we review recent studies on the effects of graphene on surface modifications of implants or scaffold materials. The ability of graphene to improve the mechanical and biological properties of implants or scaffold materials, such as nitinol and carbon nanotubes, and its ability to promote the adhesion, proliferation, and osteogenic differentiation of MSCs or osteoblasts have been demonstrated in several studies. Most previous studies were performed in vitro, but further studies will explore the mechanisms of graphene's effects on bone regeneration, its in vivo biocompatibility, its ability to promote osteodifferentiation, and its potential applications in bone tissue engineering.

Radiation-induced heart injury

International Nuclear Information System (INIS)

Suzuki, Yoshihiko; Niibe, Hideo

1975-01-01

In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

A Novel Collection of snRNA-Like Promoters with Tissue-Specific Transcription Properties

Directory of Open Access Journals (Sweden)

Aldo Pagano

2012-09-01

Full Text Available We recently identified a novel dataset of snRNA-like trascriptional units in the human genome. The investigation of a subset of these elements showed that they play relevant roles in physiology and/or pathology. In this work we expand our collection of small RNAs taking advantage of a newly developed algorithm able to identify genome sequence stretches with RNA polymerase (pol III type 3 promoter features thus constituting putative pol III binding sites. The bioinformatic analysis of a subset of these elements that map in introns of protein-coding genes in antisense configuration suggest their association with alternative splicing, similarly to other recently characterized small RNAs. Interestingly, the analysis of the transcriptional activity of these novel promoters shows that they are active in a cell-type specific manner, in accordance with the emerging body of evidence of a tissue/cell-specific activity of pol III.

Accelerated healing of cardiovascular textiles promoted by an RGD peptide.

Science.gov (United States)

Tweden, K S; Harasaki, H; Jones, M; Blevitt, J M; Craig, W S; Pierschbacher, M; Helmus, M N

1995-07-01

Polytetrafluoroethylene (PTFE) and polyethylene terephthalate (Dacron polyester) fabrics are used extensively in cardiovascular devices, e.g. heart valve sewing cuffs and vascular prostheses. While devices containing these fabrics are generally successful, it is recognized that fabrics cause complications prior to tissue ingrowth due to their thrombogenic nature. A surface active synthetic peptide, called PepTite Coating (PepTite), which was modeled after the cell attachment domain of human fibronectin has been marketed as a biocompatible coating. This peptide stimulates cell attachment through the arginine-glycine-aspartic acid (RGD) sequence. Modification of medical implants with PepTite has been shown to promote ingrowth of surrounding cells into the material leading to better tissue integration, reduced inflammation and reduced fibrotic encapsulation. In this study, polyester and PTFE textiles were modified with PepTite. The effectiveness of this coating in enhancing wound healing was investigated in a simple vascular and cardiac valve model. Our results indicate that the RGD-containing peptide, PepTite, promoted the formation of an endothelial-like cell layer on both polyester and PTFE vascular patches in the dog model. PepTite was also found to promote the formation of a significantly thinner neointima (pannus) on polyester as compared to that on its uncoated control. These results were corroborated in the cardiac valve model in which a greater amount of thin pannus and less thrombus were seen on coated polyester sewing cuffs than on control uncoated cuffs. This research shows the promising tissue response to RGD coated textiles and the potential role of this peptide in material passivation via accelerated healing.

The adaption growth of the heart in the higher age

International Nuclear Information System (INIS)

Kranz, D.; Kunde, D.; Fuhrmann, I.

1976-01-01

There was examined the influence of the age on the development of a compensatory hypertrophy of the heart in 4 to 16 month old masculin Wistar-rats autoradiographically. The valuation took place at various times after stenosing of the aorta and application of 3 H-thymidine separatly on both ventricular walls by counting of the nuclei of the marked muscle- and connective tissue cells of the heart and their mitosis. The 3 H-thymidine and mitotic index were calculated for the connective tissue cells and body and heart weight were determined. (author)

Myocardial overexpression of TIMP3 after myocardial infarction exerts beneficial effects by promoting angiogenesis and suppressing early proteolysis.

Science.gov (United States)

Takawale, Abhijit; Zhang, Pu; Azad, Abul; Wang, Wang; Wang, Xiuhua; Murray, Allan G; Kassiri, Zamaneh

2017-08-01

Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) and structural remodeling, and left ventricular (LV) dilation and dysfunction. Tissue inhibitors of metalloproteinase (TIMPs) inhibit matrix metalloproteinases (MMPs), the main regulators of ECM turnover. TIMPs also have MMP-independent functions. TIMP3 levels are reduced in the heart within 24 h of MI in mice. We investigated if overexpression of TIMP3 post-MI limits adverse remodeling and LV dilation and dysfunction. MI was induced by left anterior descending coronary artery ligation in 10- to 12-wk-old male C57BL/6J mice, and adenoviral constructs expressing human (h)TIMP3 (Ad-hTIMP3) or no TIMP (Ad-Null) were injected in the peri-infarct zone (5.4 × 10 7 plaque-forming units/heart, 5 injections/heart). Cardiac function assessed by echocardiography showed improved LV physiology and reduced LV dilation after TIMP3 overexpression compared with the Ad-Null-MI group. Post-MI adverse remodeling was attenuated in the Ad-hTIMP3-MI group, as assessed by greater cardiomyocyte density, less infarct expansion, and ECM disruption. TIMP3 overexpression blunted the early rise in proteolytic activities post-MI. A higher density of coronary arteries and a greater number of proliferating endothelial cells were detected in the infarct and peri-infarct regions in the Ad-hTIMP3-MI group compared with the Ad-Null-MI group. In vitro three-dimensional angiogenesis assay confirmed that recombinant TIMP3 promotes angiogenesis in human endothelial cells, although biphasically and in a dose-dependent manner. Intriguingly, overexpression of Ad-hTIMP3 at 10-fold higher concentration had no beneficial effects, consistent with antiangiogenic effects of TIMP3 at higher doses. In conclusion, optimal overexpression of TIMP3 can be a promising therapeutic approach to limit adverse post-MI remodeling by dually inhibiting early proteolysis and promoting angiogenesis. NEW & NOTEWORTHY Here, we report

Experimental hypothyroidism increases content of collagen and glycosaminoglycans in the heart.

Science.gov (United States)

Drobnik, J; Ciosek, J; Slotwinska, D; Stempniak, B; Zukowska, D; Marczynski, A; Tosik, D; Bartel, H; Dabrowski, R; Szczepanowska, A

2009-09-01

The connective tissue matrix of the heart remains under regulatory influence of the thyroid hormones. Some conflicting data describe the connective tissue changes in subjects with thyroid gland disorders. The aim of the study was to assess the changes of the connective tissue accumulation in the heart of rats in the state of hypothyroidism and to answer the question whether TSH is involved in mechanism of the observed phenomena. Hypothyroidism in rats was induced by methylotiouracil treatment or by thyreoidectomy. The thyroid hormones [freeT3 (fT3), freeT4 (fT4)] and pituitary TSH were measured in plasma with radioimmunological method. The glycosaminoglycans (GAG) and total collagen were measured in heart muscle of both left and right ventricles. Cells from the rat's heart were isolated and cultured. The cells were identified as myofibroblasts by electron microscopy method. The effects of TSH in concentrations ranging from 0.002 to 20 mIU/ml, on connective tissue accumulation in heart myofibroblasts cultures were tested. The primary hypothyroidism was developed both in groups with thyroidectomy and with methylthiouracil. The levels of fT3 and fT4 both in rats with thyreoidectomy and animals treated with methylthiouracil were decreased and TSH level in these two experimental groups was elevated. In the heart of the rats with experimental hypothyroidism increased content of both GAG and collagen was found. Myofibroblast number in culture was increased by TSH. Regardless of the method of its induction, hypothyroidism increased collagen and GAG contents in the heart. TSH is not involved in regulation of collagen and glycosaminoglycans accumulation in the heart of rats affected with primary hypothyroidism.

Development of a tissue engineered heart valve for pediatrics: a case study in bioengineering ethics.

Science.gov (United States)

Merryman, W David

2008-03-01

The following hypothetical case study was developed for bioengineering students and is concerned with choosing between two devices used for development of a pediatric tissue engineered heart valve (TEHV). This case is intended to elicit assessment of the devices, possible future outcomes, and ramifications of the decision making. It is framed in light of two predominant ethical theories: utilitarianism and rights of persons. After the case was presented to bioengineering graduate students, they voted on which device should be released. The results revealed that these bioengineering students preferred the more reliable (and substantially more expensive) design, though this choice precludes the majority of the world from having access to this technology. This case is intended to examine and explore where the balance lies between design, cost, and adequate distribution of biomedical devices.

Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

Energy Technology Data Exchange (ETDEWEB)

Crabbe, Rory A. [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada); Hill, Kathleen A., E-mail: khill22@uwo.ca [Department of Biology, University of Western Ontario, London, Ontario, N6A 5B7 (Canada)

2010-09-10

Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA

International Nuclear Information System (INIS)

Crabbe, Rory A.; Hill, Kathleen A.

2010-01-01

Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p < 0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.

Chromogranin A in the mammalian heart

DEFF Research Database (Denmark)

Hansen, Lasse H.; Darkner, Stine; Svendsen, Jesper H.

2017-01-01

Aim: To investigate whether chromogranin A (CgA) is secreted from the heart into circulation.  Materials & methods: Porcine cardiac tissue was analyzed for the presence of CgA-derived glycopeptides using a global O-glycoproteomic strategy. Blood was sampled from the femoral vein, right atrium...... from the heart (coronary sinus [795 pmol/l] vs left atrium [678 pmol/l]; p heart could be established (p = 0.6366).  Conclusion: The cardiac atria express but do not secrete CgA into circulation in patients with atrial disease....

Relationship between the autoantibody and expression of β3-adrenoceptor in lung and heart.

Directory of Open Access Journals (Sweden)

Guobin Miao

Full Text Available BACKGROUND: Evidences suggest that β3 -adrenoceptor (β3-AR plays an important role in heart failure (HF, although no data is reported indicating how these effects may change with the increasing age. Pulmonary congestion and edema are the major life-threatening complications associated with HF. The purpose of this study is to explore the relationship between the anti-β3-AR autoantibody and the expression of β3-AR in the lungs and heart for both aged patients and rats with HF. METHODS: Synthetic β3-AR peptides served as the target antigens in ELISA were used to screen the anti-β3-AR autoantibody in aged patients and rats. Two aged rat models were constructed based on aortic banding and sham-operation. The expression of β3-AR mRNA and protein in the lung and heart was measured in intervention and non-intervention groups by Western blot analysis at the baseline, 5(th, 7(th, 9(th and 11(th week, respectively. RESULTS: The frequency and titer of anti-β3-AR autoantibody in aged patients and rats with HF were higher than those in the control group (p<0.05. The expression of β3-AR mRNA and protein in pulmonary tissues decreased continually from the 7(th week (p<0.05, followed by HF observed during the 9(th week. The expression of β3-AR in myocardial tissues continued to increase after the 9(th week (p<0.05, and the expression of both β3-AR mRNA and protein in the BRL group [HF group with BRL37344 (4-[-[2-hydroxy-(3-chlorophenylethyl-amino] phenoxyacetic acid (a β3-AR agonist injection] was positively correlated with BRL37344 when compared with non-BRL group (HF group without BRL37344 injection (p<0.05. CONCLUSION: Anti-β3-AR autoantibody was detected in aged patients and rats with HF. The expression of β3-AR mRNA and protein in pulmonary tissues decreased continually, and began earlier than in the heart, but its expression in myocardial tissues increased continually and could be further promoted by β3-AR agonist.

Application of positron emission tomography in the heart

International Nuclear Information System (INIS)

Anon.

1988-01-01

This report discusses experimental and clinical applications of positron emission tomography to the heart, including measurements of blood flow to the myocardium and studies of metabolism and experimental injury. Most initial clinical studies have concentrated on ischemic heart disease, but the technique also has potential for investigation of cardiomyopathies, studying the neural control of the heart, and evaluating the effects of drugs on cardiac tissues

Left atrial leiomyosarcoma as cause of heart failure

International Nuclear Information System (INIS)

Valdes Martin, Alexander

2012-01-01

The case of a 26 year-old patient with diagnosis of heart failure and presence of a mobile echogenic mass without calcification attached to the posterolateral area of the left atrium was reported. She underwent surgery and tissue examination evidenced a high-grade heart leiomyosarcoma. Postoperative course was satisfactory and her clinical state was rigorously monitored by oncology and heart specialists in the institution

Biomaterials in myocardial tissue engineering

Science.gov (United States)

Reis, Lewis A.; Chiu, Loraine L. Y.; Feric, Nicole; Fu, Lara; Radisic, Milica

2016-01-01

Cardiovascular disease is the leading cause of death in the developed world, and as such there is a pressing need for treatment options. Cardiac tissue engineering emerged from the need to develop alternate sources and methods of replacing tissue damaged by cardiovascular diseases, as the ultimate treatment option for many who suffer from end-stage heart failure is a heart transplant. In this review we focus on biomaterial approaches to augment injured or impaired myocardium with specific emphasis on: the design criteria for these biomaterials; the types of scaffolds—composed of natural or synthetic biomaterials, or decellularized extracellular matrix—that have been used to develop cardiac patches and tissue models; methods to vascularize scaffolds and engineered tissue, and finally injectable biomaterials (hydrogels)designed for endogenous repair, exogenous repair or as bulking agents to maintain ventricular geometry post-infarct. The challenges facing the field and obstacles that must be overcome to develop truly clinically viable cardiac therapies are also discussed. PMID:25066525

DIFFERENTIAL RESPONSE OF HEAT SHOCK PROTEINS TO UPHILL AND DOWNHILL EXERCISE IN HEART, SKELETAL MUSCLE, LUNG AND KIDNEY TISSUES

Directory of Open Access Journals (Sweden)

Pablo C. B. Lollo

2013-09-01

Full Text Available Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP, but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric and downhill (predominantly eccentric muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7% and downhill (-7% of inclination. At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK and lactate dehydrogenase (LDH were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal. When the contraction was concentric (uphill and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL-1 in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively. The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus

Heart Rate Monitors Promote Physical Education for Children

Science.gov (United States)

Tipton, Jan; Sander, Allan N.

2004-01-01

National health and fitness data suggests that a significant percentage of children are not on a pathway to leading healthy, physically active lifestyles. Many children are leading sedentary lifestyles due to a lack of opportunity, success, or self-motivation in physical activity. Programs that highlight the use of heart rate monitors offer a…

[Ru(bipy)3]2+ nanoparticle-incorporate dental light cure resin to promote photobiomodulation therapy for enhanced vital pulp tissue repair

Science.gov (United States)

Mosca, Rodrigo C.; Young, Nicholas; Zeituni, Carlos A.; Arany, Praveen R.

2018-02-01

The use of nanoparticle on dental light cure resin is not new, currently several compounds (nanoadditives) are used to promote better communication between the restorative material and biological tissues. The interest for this application is growing up to enhance mechanical proprieties to dental tissue cells regeneration. Bioactive nanoparticles and complex compounds with multiple functions are the major target for optimizing the restorative materials. In this work, we incorporate [Ru(bipy)3]2+ nanoparticles, that absorbs energy at 450 nm (blue-light) and emits strongly at 620 nm (red-light), in PLGA Microspheres and insert it in Dental Light Cure Resin to promote the Photobiomodulation Therapy (PBM) effects to accelerate dental pulp repair by in vitro using cytotoxicity and proliferation assay.

Differential response of heat shock proteins to uphill and downhill exercise in heart, skeletal muscle, lung and kidney tissues.

Science.gov (United States)

Lollo, Pablo C B; Moura, Carolina S; Morato, Priscila N; Amaya-Farfan, Jaime

2013-01-01

Running on a horizontal plane is known to increase the concentration of the stress biomarker heat-shock protein (HSP), but no comparison of the expression of HSP70 has yet been established between the uphill (predominantly concentric) and downhill (predominantly eccentric) muscle contractions exercise. The objective of the study was to investigate the relationships between eccentric and concentric contractions on the HSP70 response of the lung, kidney, gastrocnemius, soleus and heart. Twenty-four male Wistar weanling rats were divided into four groups: non-exercised and three different grades of treadmill exercise groups: horizontal, uphill (+7%) and downhill (-7% of inclination). At the optimal time-point of six hours after the exercise, serum uric acid, creatine kinase (CK) and lactate dehydrogenase (LDH) were determined by standard methods and HSP70 by the Western blot analysis. HSP70 responds differently to different types of running. For kidney, heart, soleus and gastrocnemius, the HSP70 expression increased, 230, 180, 150 and 120% respectively of the reference (horizontal). When the contraction was concentric (uphill) and compared to downhill the increase in response of HSP70 was greater in 80% for kidney, 75% for gastrocnemius, 60% for soleus and 280% for the heart. Uric acid was about 50% higher (0.64 ± 0.03 mg·dL(-1)) in the uphill group as compared to the horizontal or downhill groups. Similarly, the activities of serum CK and LDH were both 100% greater for both the uphill and downhill groups as compared to the horizontal group (2383 ± 253 and 647.00 ± 73 U/L, respectively). The responsiveness of HSP70 appeared to be quite different depending on the type of tissue, suggesting that the impact of exercise was not restricted to the muscles, but extended to the kidney tissue. The uphill exercise increases HSP70 beyond the eccentric type and the horizontal running was a lower HSP70 responsive stimulus. Key PointsExercise can induce increases in HSP70 in

Fatty acid utilization in pressure-overload hypertrophied rat hearts

International Nuclear Information System (INIS)

Reibel, D.K.; O'Rourke, B.

1986-01-01

The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H 2 O left atrial filling pressure with a ventricular afterload of 80 cm of H 2 O with buffer containing 1.2 mM 14 C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. 14 CO 2 production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by 14 CO 2 production during this time was 0.728 +/- 0.06 μmoles/min/g dry in control hearts and 0.710 +/- 0.02 μmoles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O 2 consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 μmoles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine

Expression of cardiac neural crest and heart genes isolated by modified differential display.

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Martinsen, Brad J; Groebner, Nathan J; Frasier, Allison J; Lohr, Jamie L

2003-08-01

The invasion of the cardiac neural crest (CNC) into the outflow tract (OFT) and subsequent outflow tract septation are critical events during vertebrate heart development. We have performed four modified differential display screens in the chick embryo to identify genes that may be involved in CNC, OFT, secondary heart field, and heart development. The screens included differential display of RNA isolated from three different axial segments containing premigratory cranial neural crest cells; of RNA from distal outflow tract, proximal outflow tract, and atrioventricular tissue of embryonic chick hearts; and of RNA isolated from left and right cranial tissues, including the early heart fields. These screens have resulted in the identification of the five cDNA clones presented here, which are expressed in the cardiac neural crest, outflow tract and developing heart in patterns that are unique in heart development.

Methylation in the promoter regions of WT1, NKX6-1 and DBC1 genes in cervical cancer tissues of Uygur women in Xinjiang

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Dan Wu

Full Text Available Abstract This study aimed to explore: 1 DNA methylation in the promoter regions of Wilms tumor gene 1 (WT1, NK6 transcription factor related locus 1 gene (NKX6-1 and Deleted in bladder cancer 1 (DBC1 gene in cervical cancer tissues of Uygur women in Xinjiang, and 2 the correlation of gene methylation with the infection of HPV16/18 viruses. We detected HPV16/18 infection in 43 normal cervical tissues, 30 cervical intraepithelial neoplasia lesions (CIN and 48 cervical cancer tissues with polymerase chain reaction (PCR method. Methylation in the promoter regions of the WT1, NKX6-1 and DBC1 genes in the above-mentioned tissues was measured by methylation-specific PCR (MSP and cloning sequencing. The expression level of these three genes was measured by real-time PCR (qPCR in 10 methylation-positive cervical cancer tissues and 10 methylation-negative normal cervical tissues. We found that the infection of HPV16 in normal cervical tissues, CIN and cervical cancer tissues was 14.0, 36.7 and 66.7%, respectively. The infection of HPV18 was 0, 6.7 and 10.4%, respectively. The methylation rates of WT1, NKX6-1 and DBC1 genes were 7.0, 11.6 and 23.3% in normal cervical tissues, 36.7, 46.7 and 30.0% in CIN tissues, and 89.6, 77.1 and 85.4% in cervical cancer tissues. Furthermore, WT1, NKX6-1 and DBC1 genes were hypermethylated in the high-grade squamous intraepithelial lesion (CIN2, CIN3 and in the cervical cancer tissues with infection of HPV16/18 (both P< 0.05. The expression of WT1, NKX6-1 and DBC1 was significantly lower in the methylation-positive cervical cancer tissues than in methylation-negative normal cervical tissues. Our findings indicated that methylation in the promoter regions of WT1, NKX6-1 and DBC1 is correlated with cervical cancer tumorigenesis in Uygur women. The infection of HPV16/18 might be correlated with methylation in these genes. Gene inactivation caused by methylation might be related to the incidence and development of cervical

Towards robot-assisted anchor deployment in beating-heart mitral valve surgery.

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Cheng, Lingbo; Sharifi, Mojtaba; Tavakoli, Mahdi

2018-06-01

Beating-heart intracardiac surgery promises significant benefits for patients compared with cardiopulmonary bypass based procedures. However, the fast motions of the heart introduce serious challenges for surgeons. In this work, a new impedance-controlled master-slave telerobotic system is developed to help perform anchor deployment for mitral valve annuloplasty under the guidance of live ultrasound images of the heart. The proposed bilateral teleoperation system can both reflect the non-oscillatory portion of slave-heart tissue interaction force on the surgeon's hand as haptic feedback and implement rapid compensation for the beating heart's motion. The surgical task involves performing anchor deployment on a simulated moving heart tissue to evaluate the effectiveness of the proposed strategy for safely interacting with a moving organ. The results obtained show that the telerobotic system increases the success rate of anchor deployment by 100% and reduces the excess force application rate by 70% compared with manual attempts. Copyright © 2018 John Wiley & Sons, Ltd.

Proangiogenic scaffolds as functional templates for cardiac tissue engineering.

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Madden, Lauran R; Mortisen, Derek J; Sussman, Eric M; Dupras, Sarah K; Fugate, James A; Cuy, Janet L; Hauch, Kip D; Laflamme, Michael A; Murry, Charles E; Ratner, Buddy D

2010-08-24

We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30-40 microm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response.

Development of an angiogenesis-promoting microvesicle-alginate-polycaprolactone composite graft for bone tissue engineering applications

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Hui Xie

2016-05-01

Full Text Available One of the major challenges of bone tissue engineering applications is to construct a fully vascularized implant that can adapt to hypoxic environments in vivo. The incorporation of proangiogenic factors into scaffolds is a widely accepted method of achieving this goal. Recently, the proangiogenic potential of mesenchymal stem cell-derived microvesicles (MSC-MVs has been confirmed in several studies. In the present study, we incorporated MSC-MVs into alginate-polycaprolactone (PCL constructs that had previously been developed for bone tissue engineering applications, with the aim of promoting angiogenesis and bone regeneration. MSC-MVs were first isolated from the supernatant of rat bone marrow-derived MSCs and characterized by scanning electron microscopic, confocal microscopic, and flow cytometric analyses. The proangiogenic potential of MSC-MVs was demonstrated by the stimulation of tube formation of human umbilical vein endothelial cells in vitro. MSC-MVs and osteodifferentiated MSCs were then encapsulated with alginate and seeded onto porous three-dimensional printed PCL scaffolds. When combined with osteodifferentiated MSCs, the MV-alginate-PCL constructs enhanced vessel formation and tissue-engineered bone regeneration in a nude mouse subcutaneous bone formation model, as demonstrated by micro-computed tomographic, histological, and immunohistochemical analyses. This MV-alginate-PCL construct may offer a novel, proangiogenic, and cost-effective option for bone tissue engineering.

A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice

International Nuclear Information System (INIS)

Pittius, C.W.; Hennighausen, L.; Lee, E.; Westphal, H.; Nicols, E.; Vitale, J.; Gordon, K.

1988-01-01

Whey acidic protein (WAP) is a major whey protein in mouse milk. Its gene is expressed in the lactating mammary gland and is inducible by steroid and peptide hormones. A series of transgenic mice containing a hybrid gene in which human tissue plasminogen activator (tPA) cDNA is under the control of the murine WAP gene promoter had previously been generated. In this study, 21 tissues from lactating and virgin transgenic female mice containing the WAP-tPA hybrid gene were screened for the distribution of murine WAP and human tPA transcripts. Like the endogenous WAP RNA, WAP-tPA RNA was expressed predominantly in mammary gland tissue and appeared to be inducible by lactation. Whereas WAP transcripts were not detected in 22 tissues of virgin mice, low levels of WAP-tPA RNA, which were not modulated during lactation, were found in tongue, kidney, and sublingual gland. These studies demonstrate that the WAP gene promoter can target the expression of a transgene to the mammary gland and that this expression is inducible during lactation

Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

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Packer, Milton

2018-04-10

Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits. © 2018 American Heart Association, Inc.

Curcumin mediated attenuation of carbofuran induced toxicity in the heart of Wistar rats.

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Jaiswal, S K; Gupta, V K; Siddiqi, N J; Sharma, B

2017-07-31

Carbofuran is used to improve the agricultural productivity as well as to protect the house hold and industrial products, but due to accumulation in the biological system, it causes serious side effects in many non-targets mammalian systems. The aim of present study is to evaluate the carbofuran induced oxidative stress in rat heart and its attenuation by using herbal product curcumin. Rats were divided into four groups; one group received 20 % LD50 of carbofuran another group of rats received same doses of carbofuran was  pretreated with curcumin (100 mg kg-1 body weight) and remaining two other groups served as control and curcumin treated animals. The activity of lactate dehydrogenase (LDH) in the heart tissues and serum was evaluated and the activity of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) was estimated in the heart tissues. The level of malondialdehyde (MDA) in heart tissues was also measured. The Total cholesterol (TC) and high density lipoprotein (HDL) was measured in the serum of the entire animals group. The results of present study showed that the activity of LDH in heart tissues were decreased and in serum was elevated. The MDA level was significantly elevated due to exposure of carbofuran. The enzymatic antioxidants, SOD and CAT activities were also inhibited. The ratio of pro-oxidant (P)/antioxidant (A) was also found to be sharply increased in the rat heart tissues of carbofuran exposed animals. The alterations in all the parameter were recovered by the pretreatment of curcumin (100 mg kg-1 body weight).

Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

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Gallyamov, Marat O., E-mail: glm@spm.phys.msu.ru [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Chaschin, Ivan S. [Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Khokhlova, Marina A. [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Grigorev, Timofey E. [Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation); Bakuleva, Natalia P.; Lyutova, Irina G.; Kondratenko, Janna E. [Bakulev Scientific Center for Cardiovascular Surgery of the Russian Academy of Medical Sciences, Roublyevskoe Sh. 135, Moscow 121552 (Russian Federation); Badun, Gennadii A.; Chernysheva, Maria G. [Radiochemistry Division, Faculty of Chemistry, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Khokhlov, Alexei R. [Faculty of Physics, Lomonosov Moscow State University, Leninskie gory 1–2, Moscow 119991 (Russian Federation); Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilova 28, Moscow 119991 (Russian Federation)

2014-04-01

Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H{sub 2}O and CO{sub 2}. Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1 wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid. - Highlights: • Treatment of GA

Collagen tissue treated with chitosan solutions in carbonic acid for improved biological prosthetic heart valves

International Nuclear Information System (INIS)

Gallyamov, Marat O.; Chaschin, Ivan S.; Khokhlova, Marina A.; Grigorev, Timofey E.; Bakuleva, Natalia P.; Lyutova, Irina G.; Kondratenko, Janna E.; Badun, Gennadii A.; Chernysheva, Maria G.; Khokhlov, Alexei R.

2014-01-01

Calcification of bovine pericardium dramatically shortens typical lifetimes of biological prosthetic heart valves and thus precludes their choice for younger patients. The aim of the present work is to demonstrate that the calcification is to be mitigated by means of treatment of bovine pericardium in solutions of chitosan in carbonic acid, i.e. water saturated with carbon dioxide at high pressure. This acidic aqueous fluid unusually combines antimicrobial properties with absolute biocompatibility as far as at normal pressure it decomposes spontaneously and completely into H 2 O and CO 2 . Yet, at high pressures it can protonate and dissolve chitosan materials with different degrees of acetylation (in the range of 16–33%, at least) without any further pretreatment. Even exposure of the bovine pericardium in pure carbonic acid solution without chitosan already favours certain reduction in calcification, somewhat improved mechanical properties, complete biocompatibility and evident antimicrobial activity of the treated collagen tissue. The reason may be due to high extraction ability of this peculiar compressed fluidic mixture. Moreover, exposure of the bovine pericardium in solutions of chitosan in carbonic acid introduces even better mechanical properties and highly pronounced antimicrobial activity of the modified collagen tissue against adherence and biofilm formation of relevant Gram-positive and Gram-negative strains. Yet, the most important achievement is the detected dramatic reduction in calcification for such modified collagen tissues in spite of the fact that the amount of the thus introduced chitosan is rather small (typically ca. 1 wt.%), which has been reliably detected using original tritium labelling method. We believe that these improved properties are achieved due to particularly deep and uniform impregnation of the collagen matrix with chitosan from its pressurised solutions in carbonic acid. - Highlights: • Treatment of GA-stabilised bovine

Adverse fibrosis in the aging heart depends on signaling between myeloid and mesenchymal cells; role of inflammatory fibroblasts.

Science.gov (United States)

Cieslik, Katarzyna A; Trial, JoAnn; Crawford, Jeffrey R; Taffet, George E; Entman, Mark L

2014-05-01

Aging has been associated with adverse fibrosis. Here we formulate a new hypothesis and present new evidence that unresponsiveness of mesenchymal stem cells (MSC) and fibroblasts to transforming growth factor beta (TGF-β), due to reduced expression of TGF-β receptor I (TβRI), provides a foundation for cardiac fibrosis in the aging heart via two mechanisms. 1) TGF-β promotes expression of Nanog, a transcription factor that retains MSC in a primitive state. In MSC derived from the aging heart, Nanog expression is reduced and therefore MSC gradually differentiate and the number of mesenchymal fibroblasts expressing collagen increases. 2) As TGF-β signaling pathway components negatively regulate transcription of monocyte chemoattractant protein-1 (MCP-1), a reduced expression of TβRI prevents aging mesenchymal cells from shutting down their own MCP-1 expression. Elevated MCP-1 levels that originated from MSC attract transendothelial migration of mononuclear leukocytes from blood to the tissue. MCP-1 expressed by mesenchymal fibroblasts promotes further migration of monocytes and T lymphocytes away from the endothelial barrier and supports the monocyte transition into macrophages and finally into myeloid fibroblasts. Both myeloid and mesenchymal fibroblasts contribute to fibrosis in the aging heart via collagen synthesis. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium ". © 2013. Published by Elsevier Ltd. All rights reserved.

Whey protein and essential amino acids promote the reduction of adipose tissue and increased muscle protein synthesis during caloric restriction-induced weight loss in elderly, obese individuals

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Coker Robert H

2012-12-01

Full Text Available Abstract Background Excess adipose tissue and sarcopenia presents a multifaceted clinical challenge that promotes morbidity and mortality in the obese, elderly population. Unfortunately, the mortality risks of muscle loss may outweigh the potential benefits of weight loss in the elderly. We have previously demonstrated the effectiveness of whey protein and essential amino acids towards the preservation of lean tissue, even under the conditions of strict bedrest in the elderly. Methods In the context of caloric restriction-based weight loss, we hypothesized that a similar formulation given as a meal replacement (EAAMR would foster the retention of lean tissue through an increase in the skeletal muscle fractional synthesis rate (FSR. We also proposed that EAAMR would promote the preferential loss of adipose tissue through the increased energy cost of skeletal muscle FSR. We recruited and randomized 12 elderly individuals to an 8 week, caloric restriction diet utilizing equivalent caloric meal replacements (800 kcal/day: 1 EAAMR or a 2 competitive meal replacement (CMR in conjunction with 400 kcal of solid food that totaled 1200 kcal/day designed to induce 7% weight loss. Combined with weekly measurements of total body weight and body composition, we also measured the acute change in the skeletal muscle FSR to EAAMR and CMR. Results By design, both groups lost ~7% of total body weight. While EAAMR did not promote a significant preservation of lean tissue, the reduction in adipose tissue was greater in EAAMR compared to CMR. Interestingly, these results corresponded to an increase in the acute skeletal muscle protein FSR. Conclusion The provision of EAAMR during caloric restriction-induced weight loss promotes the preferential reduction of adipose tissue and the modest loss of lean tissue in the elderly population.

[Effect of melaxen and valdoxan on free radical processes intensity, aconitate hydratase activity and citrate content in rats tissues under hyperthyroidism].

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Gorbenko, M V; Popova, T N; Shul'gin, K K; Popov, S S; Agarkov, A A

2014-01-01

The influence of melaxen and valdoxan on the biochemiluminescence parameters, aconitate hydratase activity and citrate level in rats heart and liver during development of experimental hyperthyroidism has been investigated. Administration of these substances promoted a decrease of biochemiluminescence parameters, which had been increased in tissues of rats in response to the development of oxidative stress under hyperthyroidism. Aconitate hydratase activity and citrate concentration in rats liver and heart, growing at pathological conditions, changed towards control value after administration of the drugs correcting melatonin level. The results indicate the positive effect of valdoxan and melaxen on oxidative status of the organism under the development of experimental hyperthyroidism that is associated with antioxidant action of melatonin.

Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.

Science.gov (United States)

Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

2013-07-01

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (Pregional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. Published by Elsevier

Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure

International Nuclear Information System (INIS)

Ye, Lusi; Jiang, Ying; Zuo, Xiaoxia

2015-01-01

Objective: The farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control. Methods and results: Hemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAH (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues. Conclusions: The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH. - Highlights: • FXR was expressed in rat lung and heart tissues. • FXR expression increased sharply in the lung tissues of PAH and RHF rats. • FXR expression was reduced in PAH and RHF rat RV tissue. • FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue. • FXR expression was prominent in the neovascularization region.

Farnesoid-X-receptor expression in monocrotaline-induced pulmonary arterial hypertension and right heart failure

Energy Technology Data Exchange (ETDEWEB)

Ye, Lusi [Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China); Department of Rheumatology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325015 (China); Jiang, Ying [Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China); Zuo, Xiaoxia, E-mail: susanzuo@hotmail.com [Department of Rheumatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008 (China)

2015-11-06

Objective: The farnesoid-X-receptor (FXR) is a metabolic nuclear receptor superfamily member that is highly expressed in enterohepatic tissue and is also expressed in the cardiovascular system. Multiple nuclear receptors, including FXR, play a pivotal role in cardiovascular disease (CVD). Pulmonary arterial hypertension (PAH) is an untreatable cardiovascular system disease that leads to right heart failure (RHF). However, the potential physiological/pathological roles of FXR in PAH and RHF are unknown. We therefore compared FXR expression in the cardiovascular system in PAH, RHF and a control. Methods and results: Hemodynamic parameters and morphology were assessed in blank solution-exposed control, monocrotaline (MCT)-exposed PAH (4 weeks) and RHF (7 weeks) Sprague–Dawley rats. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR), Western blot (WB), immunohistochemistry (IHC) analysis and immunofluorescence (IF) analysis were performed to assess FXR levels in the lung and heart tissues of MCT-induced PAH and RHF rats. In normal rats, low FXR levels were detected in the heart, and nearly no FXR was expressed in rat lungs. However, FXR expression was significantly elevated in PAH and RHF rat lungs but reduced in PAH and RHF rat right ventricular (RV) tissues. FXR expression was reduced only in RHF rat left ventricular (LV) tissues. Conclusions: The differential expression of FXR in MCT-induced PAH lungs and heart tissues in parallel with PAH pathophysiological processes suggests that FXR contributes to PAH. - Highlights: • FXR was expressed in rat lung and heart tissues. • FXR expression increased sharply in the lung tissues of PAH and RHF rats. • FXR expression was reduced in PAH and RHF rat RV tissue. • FXR expression was unaltered in PAH LV but reduced in RHF rat LV tissue. • FXR expression was prominent in the neovascularization region.

A novel customizable modular bioreactor system for whole-heart cultivation under controlled 3D biomechanical stimulation.

Science.gov (United States)

Hülsmann, Jörn; Aubin, Hug; Kranz, Alexander; Godehardt, Erhardt; Munakata, Hiroshi; Kamiya, Hiroyuki; Barth, Mareike; Lichtenberg, Artur; Akhyari, Payam

2013-09-01

In the last decade, cardiovascular tissue engineering has made great progress developing new strategies for regenerative medicine applications. However, while tissue engineered heart valves are already entering the clinical routine, tissue engineered myocardial substitutes are still restrained to experimental approaches. In contrast to the heart valves, tissue engineered myocardium cannot be repopulated in vivo because of its biological complexity, requiring elaborate cultivation conditions ex vivo. Although new promising approaches-like the whole-heart decellularization concept-have entered the myocardial tissue engineering field, bioreactor technology needed for the generation of functional myocardial tissue still lags behind in the sense of user-friendly, flexible and low cost systems. Here, we present a novel customizable modular bioreactor system that can be used for whole-heart cultivation. Out of a commercially obtainable original equipment manufacturer platform we constructed a modular bioreactor system specifically aimed at the cultivation of decellularized whole-hearts through perfusion and controlled 3D biomechanical stimulation with a simple but highly flexible operation platform based on LabVIEW. The modular setup not only allows a wide range of variance regarding medium conditioning under controlled 3D myocardial stretching but can also easily be upgraded for e.g. electrophysiological monitoring or stimulation, allowing for a tailor-made low-cost myocardial bioreactor system.

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

International Nuclear Information System (INIS)

Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

2015-01-01

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

Energy Technology Data Exchange (ETDEWEB)

Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

2015-08-14

Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

Promoter methylation and age-related downregulation of Klotho in rhesus monkey.

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King, Gwendalyn D; Rosene, Douglas L; Abraham, Carmela R

2012-12-01

While overall DNA methylation decreases with age, CpG-rich areas of the genome can become hypermethylated. Hypermethylation near transcription start sites typically decreases gene expression. Klotho (KL) is important in numerous age-associated pathways including insulin/IGF1 and Wnt signaling and naturally decreases with age in brain, heart, and liver across species. Brain tissues from young and old rhesus monkeys were used to determine whether epigenetic modification of the KL promoter underlies age-related decreases in mRNA and protein levels of KL. The KL promoter in genomic DNA from brain white matter did not show evidence of oxidation in vivo but did exhibit an increase in methylation with age. Further analysis identified individual CpG motifs across the region of interest with increased methylation in old animals. In vitro methyl modification of these individual cytosine residues confirmed that methylation of the promoter can decrease gene transcription. These results provide evidence that changes in KL gene expression with age may, at least in part, be the result of epigenetic changes to the 5' regulatory region.

A genome-wide study of DNA methylation patterns and gene expression levels in multiple human and chimpanzee tissues.

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Athma A Pai

2011-02-01

Full Text Available The modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. Methylation patterns have been described in many contexts within and across a range of species. However, the extent to which changes in methylation might underlie inter-species differences in gene regulation, in particular between humans and other primates, has not yet been studied. To this end, we studied DNA methylation patterns in livers, hearts, and kidneys from multiple humans and chimpanzees, using tissue samples for which genome-wide gene expression data were also available. Using the multi-species gene expression and methylation data for 7,723 genes, we were able to study the role of promoter DNA methylation in the evolution of gene regulation across tissues and species. We found that inter-tissue methylation patterns are often conserved between humans and chimpanzees. However, we also found a large number of gene expression differences between species that might be explained, at least in part, by corresponding differences in methylation levels. In particular, we estimate that, in the tissues we studied, inter-species differences in promoter methylation might underlie as much as 12%-18% of differences in gene expression levels between humans and chimpanzees.

Phase analysis of circadian-related genes in two tissues

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Li Leping

2006-02-01

Full Text Available Abstract Background Recent circadian clock studies using gene expression microarray in two different tissues of mouse have revealed not all circadian-related genes are synchronized in phase or peak expression times across tissues in vivo. Instead, some circadian-related genes may be delayed by 4–8 hrs in peak expression in one tissue relative to the other. These interesting biological observations prompt a statistical question regarding how to distinguish the synchronized genes from genes that are systematically lagged in phase/peak expression time across two tissues. Results We propose a set of techniques from circular statistics to analyze phase angles of circadian-related genes in two tissues. We first estimate the phases of a cycling gene separately in each tissue, which are then used to estimate the paired angular difference of the phase angles of the gene in the two tissues. These differences are modeled as a mixture of two von Mises distributions which enables us to cluster genes into two groups; one group having synchronized transcripts with the same phase in the two tissues, the other containing transcripts with a discrepancy in phase between the two tissues. For each cluster of genes we assess the association of phases across the tissue types using circular-circular regression. We also develop a bootstrap methodology based on a circular-circular regression model to evaluate the improvement in fit provided by allowing two components versus a one-component von-Mises model. Conclusion We applied our proposed methodologies to the circadian-related genes common to heart and liver tissues in Storch et al. 2, and found that an estimated 80% of circadian-related transcripts common to heart and liver tissues were synchronized in phase, and the other 20% of transcripts were lagged about 8 hours in liver relative to heart. The bootstrap p-value for being one cluster is 0.063, which suggests the possibility of two clusters. Our methodologies can

Functional role of voltage gated Ca2+ channels in heart automaticity

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Pietro eMesirca

2015-02-01

Full Text Available Pacemaker activity of automatic cardiac myocytes controls the heartbeat in everyday life. Cardiac automaticity is under the control of several neurotransmitters and hormones and is constantly regulated by the autonomic nervous system to match the physiological needs of the organism. Several classes of ion channels and proteins involved in intracellular Ca2+ dynamics contribute to pacemaker activity. The functional role of voltage-gated calcium channels (VGCCs in heart automaticity and impulse conduction has been matter of debate for 30 years. However, growing evidence shows that VGCCs are important regulators of the pacemaker mechanisms and play also a major role in atrio-ventricular impulse conduction. Incidentally, studies performed in genetically modified mice lacking L-type Cav1.3 (Cav1.3-/- or T-type Cav3.1 (Cav3.1-/- channels show that genetic inactivation of these channels strongly impacts pacemaking. In cardiac pacemaker cells, VGCCs activate at negative voltages at the beginning of the diastolic depolarization and importantly contribute to this phase by supplying inward current. Loss-of-function of these channels also impairs atrio-ventricular conduction. Furthermore, inactivation of Cav1.3 channels promotes also atrial fibrillation and flutter in knockout mice suggesting that these channels can play a role in stabilizing atrial rhythm. Genomic analysis demonstrated that Cav1.3 and Cav3.1 channels are widely expressed in pacemaker tissue of mice, rabbits and humans. Importantly, human diseases of pacemaker activity such as congenital bradycardia and heart block have been attributed to loss-of-function of Cav1.3 and Cav3.1 channels. In this article, we will review the current knowledge on the role of VGCCs in the generation and regulation of heart rate and rhythm. We will discuss also how loss of Ca2+ entry through VGCCs could influence intracellular Ca2+ handling and promote atrial arrhythmias.

Applying the Health Belief Model and an Integrated Behavioral Model to Promote Breast Tissue Donation Among Asian Americans.

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Shafer, Autumn; Kaufhold, Kelly; Luo, Yunjuan

2018-07-01

An important part in the effort to prevent, treat, and cure breast cancer is research done with healthy breast tissue. The Susan G. Komen for the Cure Tissue Bank at Indiana University Simon Cancer Center (KTB) encourages women to donate a small amount of healthy breast tissue and then provides that tissue to researchers studying breast cancer. Although KTB has a large donor base, the volume of tissue samples from Asian women is low despite prior marketing efforts to encourage donation among this population. This study builds on prior work promoting breast cancer screenings among Asian women by applying constructs from the Health Belief Model (HBM) and the Integrated Behavioral Model (IBM) to investigate why Asian-American women are less inclined to donate their healthy breast tissue than non-Asian women and how this population may be motivated to donate in the future. A national online survey (N = 1,317) found Asian women had significantly lower perceived severity, some lower perceived benefits, and higher perceived barriers to tissue donation than non-Asian women under HBM and significantly lower injunctive norms supporting breast tissue donation, lower perceived behavioral control, and lower intentions to donate under IBM. This study also compares and discusses similarities and differences among East, Southeast, and South Asian women on these same constructs.

Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

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Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

2015-08-24

Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Tissue

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David Morrissey

2012-01-01

Full Text Available Purpose. In vivo gene therapy directed at tissues of mesenchymal origin could potentially augment healing. We aimed to assess the duration and magnitude of transene expression in vivo in mice and ex vivo in human tissues. Methods. Using bioluminescence imaging, plasmid and adenoviral vector-based transgene expression in murine quadriceps in vivo was examined. Temporal control was assessed using a doxycycline-inducible system. An ex vivo model was developed and optimised using murine tissue, and applied in ex vivo human tissue. Results. In vivo plasmid-based transgene expression did not silence in murine muscle, unlike in liver. Although maximum luciferase expression was higher in muscle with adenoviral delivery compared with plasmid, expression reduced over time. The inducible promoter cassette successfully regulated gene expression with maximum levels a factor of 11 greater than baseline. Expression was re-induced to a similar level on a temporal basis. Luciferase expression was readily detected ex vivo in human muscle and tendon. Conclusions. Plasmid constructs resulted in long-term in vivo gene expression in skeletal muscle, in a controllable fashion utilising an inducible promoter in combination with oral agents. Successful plasmid gene transfection in human ex vivo mesenchymal tissue was demonstrated for the first time.

Radiation-induced heart injury. Radiopathological study

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Suzuki, Y; Niibe, H [Gunma Univ., Maebashi (Japan). School of Medicine

1975-11-01

In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the interval between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue.

HeartMath and Ubuntu integral healing approaches for social ...

African Journals Online (AJOL)

HeartMath and Ubuntu integral healing approaches for social coherence and physical activity. Stephen D. Edwards. Abstract. This research was motivated by many social health problems confronting planet earth. Its aim is to introduce HeartMath and Ubuntu as complimentary, integral healing approaches for promoting ...

Dynamic positional fate map of the primary heart-forming region.

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Cui, Cheng; Cheuvront, Tracey J; Lansford, Rusty D; Moreno-Rodriguez, Ricardo A; Schultheiss, Thomas M; Rongish, Brenda J

2009-08-15

Here we show the temporal-spatial orchestration of early heart morphogenesis at cellular level resolution, in vivo, and reconcile conflicting positional fate mapping data regarding the primary heart-forming field(s). We determined the positional fates of precardiac cells using a precision electroporation approach in combination with wide-field time-lapse microscopy in the quail embryo, a warm-blooded vertebrate (HH Stages 4 through 10). Contrary to previous studies, the results demonstrate the existence of a "continuous" circle-shaped heart field that spans the midline, appearing at HH Stage 4, which then expands to form a wide arc of progenitors at HH Stages 5-7. Our time-resolved image data show that a subset of these cardiac progenitor cells do not overlap with the expression of common cardiogenic factors, Nkx-2.5 and Bmp-2, until HH Stage 10, when a tubular heart has formed, calling into question when cardiac fate is specified and by which key factors. Sub-groups and anatomical bands (cohorts) of heart precursor cells dramatically change their relative positions in a process largely driven by endodermal folding and other large-scale tissue deformations. Thus, our novel dynamic positional fate maps resolve the origin of cardiac progenitor cells in amniotes. The data also establish the concept that tissue motion contributes significantly to cellular position fate - i.e., much of the cellular displacement that occurs during assembly of a midline heart tube (HH Stage 9) is NOT due to "migration" (autonomous motility), a commonly held belief. Computational analysis of our time-resolved data lays the foundation for more precise analyses of how cardiac gene regulatory networks correlate with early heart tissue morphogenesis in birds and mammals.

Promotion of Wound Healing by an Agonist of Adenosine A2A Receptor Is Dependent on Tissue Plasminogen Activator.

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Montesinos, M Carmen; Desai-Merchant, Avani; Cronstein, Bruce N

2015-12-01

Impaired wound healing, as it occurs in diabetes mellitus or long-term corticoid treatment, is commonly associated with disability, diminished quality of life, and high economic costs. Selective agonists of the A2A receptor subtype of adenosine, an endogenous regulator of inflammation, promote tissue repair in animal models, both healthy and with impaired healing. Plasmin-mediated proteolysis of fibrin and other matrix proteins is essential for cell migration at sites of injury. Since adenosine A2A receptor activation increases plasminogen activator release from macrophages and mast cells, we studied the effect of a selective agonist, CGS-21680, on full-thickness excisional wound closure in wild-type, urokinase plasminogen activator (uPA)-deficient, and tissue plasminogen activator (tPA)-deficient mice. Wound closure was impaired in tPA- and uPA-deficient mice as compared with wild-type mice, and topical application of CGS-21680 significantly increased the rate at which wounds closed in wild-type mice and uPA-deficient mice, but not in tPA-deficient mice. Immunostaining of tissue sections showed that tPA was present in endothelial cells and histiocytes by day 3 post-wound and also by day 6. In contrast, uPA was more prominent in these cell types only by day 6 post-wound. Our results confirm that plasminogen activation contributes to wound repair and are consistent with the hypothesis that adenosine A2A receptor activation promotes wound closure by a mechanism that depends upon tPA, but not uPA. Moreover, our results suggest that topical adenosine A2A receptor agonists may be useful in promotion of wound closure in patients with impaired wound healing.

Pairwise comparisons of ten porcine tissues identify differential transcriptional regulation at the gene, isoform, promoter and transcription start site level

DEFF Research Database (Denmark)

Farajzadeh, Leila; Hornshøj, Henrik; Momeni, Jamal

2013-01-01

, isoform, and transcription start site (TSS), and promoter level showed that several of the genes differed at all four levels. Interestingly, these genes were mainly annotated to the "electron transport chain" and neuronal differentiation, emphasizing that "tissue important" genes are regulated at several...

Necrotizing infection of the heart.

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Ballard, David H; Pennington, George Patton; Pennington, George P; Johnson, Joe; Bhalla, Sanjeev; Raptis, Constantine

2018-02-06

A case of necrotizing infection of the heart is presented. A 70-year-old woman presented with vague chest and abdominal pain. CT of the abdomen and pelvis was initially obtained, which demonstrated gas in the myocardium of the left ventricle. Subsequent chest CT, endoscopy, and abdominal surgical exploration did not reveal perforated viscus or diaphragm compromise. At median sternotomy, the inferior wall of the heart was found to be necrotic. Culture of the excised tissue grew E. coli. The patient expired shortly after surgical exploration. Copyright © 2018 Elsevier Inc. All rights reserved.

Acute, massive pulmonary embolism with right heart strain and hypoxia requiring emergent tissue plasminogen activator (TPA infusion

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Jonathan Patane

2017-04-01

Full Text Available History of present illness: A 63-year-old male presented to the emergency department with shortness of breath. He had a history of prostate cancer and two previous pulmonary embolisms, but was not currently on blood thinners. He had no associated chest pain at the time of presentation, but endorsed hemoptysis. Vital signs were significant for a heart rate of 88, blood pressure 145/89, oxygen saturation in the mid-70’s on room air which increased to mid-80’s on 15L facemask. His exam was significant for clear lung sounds bilaterally. He immediately underwent chest x-ray which showed no acute abnormalities. A bedside ultrasound was performed which showed evidence of right ventricular and atrial dilation, consistent with right heart strain. Given that the patient’s oxygen saturations improved to 88% on 15L facemask, the patient was felt to be stable enough for CT angiography. Significant findings: CT angiogram showed multiple large acute pulmonary emboli, most significantly in the distal right main pulmonary artery (image 1 and 2. Additional pulmonary emboli were noted in the bilateral lobar, segmental, and subsegmental levels of all lobes. There was a peripheral, wedge-shaped consolidation surrounded by groundglass changes in the posterolateral basal right lower lobe that was consistent with a small lung infarction (image 3. Discussion: The patient underwent in the Emergency Department a tissue plasminogen activator (TPA infusion of alteplase 100 mg over 2 hours for his massive acute pulmonary embolisms. Throughout his TPA infusion his oxygen saturations became improved to mid-90’s and his shortness of breath symptoms began improving. His troponin returned at 0.15 ng/mL, suggesting right heart strain. He was admitted to the ICU for continued monitoring and treatment. An acute, massive pulmonary embolism is described as having more than 50% occlusion of pulmonary blood flow.1 The main causes of hypoxia includes ventilation

Epicardium-Derived Heart Repair

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Anke M. Smits

2014-04-01

Full Text Available In the last decade, cell replacement therapy has emerged as a potential approach to treat patients suffering from myocardial infarction (MI. The transplantation or local stimulation of progenitor cells with the ability to form new cardiac tissue provides a novel strategy to overcome the massive loss of myocardium after MI. In this regard the epicardium, the outer layer of the heart, is a tractable local progenitor cell population for therapeutic pursuit. The epicardium has a crucial role in formation of the embryonic heart. After activation and migration into the developing myocardium, epicardial cells differentiate into several cardiac cells types. Additionally, the epicardium provides instructive signals for the growth of the myocardium and coronary angiogenesis. In the adult heart, the epicardium is quiescent, but recent evidence suggests that it becomes reactivated upon damage and recapitulates at least part of its embryonic functions. In this review we provide an update on the current knowledge regarding the contribution of epicardial cells to the adult mammalian heart during the injury response.

Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

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Kaytlyn A Gerbin

Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

Cardiac macrophages adopt profibrotic/M2 phenotype in infarcted hearts: Role of urokinase plasminogen activator.

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Carlson, Signe; Helterline, Deri; Asbe, Laura; Dupras, Sarah; Minami, Elina; Farris, Stephen; Stempien-Otero, April

2017-07-01

Macrophages (mac) that over-express urokinase plasminogen activator (uPA) adopt a profibrotic M2 phenotype in the heart in association with cardiac fibrosis. We tested the hypothesis that cardiac macs are M2 polarized in infarcted mouse and human hearts and that polarization is dependent on mac-derived uPA. Studies were performed using uninjured (UI) or infarcted (MI) hearts of uPA overexpressing (SR-uPA), uPA null, or nontransgenic littermate (Ntg) mice. At 7days post-infarction, cardiac mac were isolated, RNA extracted and M2 markers Arg1, YM1, and Fizz1 measured with qrtPCR. Histologic analysis for cardiac fibrosis, mac and myofibroblasts was performed at the same time-point. Cardiac macs were also isolated from Ntg hearts and RNA collected after primary isolation or culture with vehicle, IL-4 or plasmin and M2 marker expression measured. Cardiac tissue and blood was collected from humans with ischemic heart disease. Expression of M2 marker CD206 and M1 marker TNFalpha was measured. Macs from WT mice had increased expression of Arg1 and Ym1 following MI (41.3±6.5 and 70.3±36, fold change vs UI, n=8, Padopt a M2 phenotype in association with fibrosis. Plasmin can induce an M2 phenotype in cardiac macs. However, M2 activation can occur in the heart in vivo in the absence of uPA indicating that alternative pathways to activate plasmin are present in the heart. Excess uPA promotes increased fibroblast density potentially via potentiating fibroblast migration or proliferation. Altering macrophage phenotype in the heart is a potential target to modify cardiac fibrosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hydroxytyrosol and its complex forms (secoiridoids) modulate aorta and heart proteome in healthy rats: Potential cardio-protective effects.

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Catalán, Úrsula; Rubió, Laura; López de Las Hazas, Maria-Carmen; Herrero, Pol; Nadal, Pedro; Canela, Núria; Pedret, Anna; Motilva, Maria-José; Solà, Rosa

2016-10-01

Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in both free and complex forms (secoiridoids; SEC). Proteomics of cardiovascular tissues such as aorta or heart represents a promising tool to uncover the mechanisms of action of phenolic compounds in healthy animals. Twelve female Wistar rats were separated into three groups: a standard diet and two diets supplemented in phenolic compounds (HT and SEC) adjusted to 5 mg/kg/day during 21 days. Proteomic analyses of aorta and heart tissues were performed by nano-LC and MS. Ingenuity Pathway Analysis was used to generate interaction networks. HT or SEC modulated aorta and heart proteome compared to the standard diet. The top-scored networks were related to Cardiovascular System. HT and SEC downregulated proteins related to proliferation and migration of endothelial cells and occlusion of blood vessels in aorta and proteins related to heart failure in heart tissue. SEC showed higher fold change values compared to HT, attributed to higher concentration of HT detected in heart tissue. Changes at proteomic level in cardiovascular tissues may partially account for the underlying mechanisms of VOO phenols cardiovascular protection being the SEC effects higher than free HT. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tissue Engineering Strategies for Myocardial Regeneration: Acellular Versus Cellular Scaffolds?

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Domenech, Maribella; Polo-Corrales, Lilliana; Ramirez-Vick, Jaime E; Freytes, Donald O

2016-12-01

Heart disease remains one of the leading causes of death in industrialized nations with myocardial infarction (MI) contributing to at least one fifth of the reported deaths. The hypoxic environment eventually leads to cellular death and scar tissue formation. The scar tissue that forms is not mechanically functional and often leads to myocardial remodeling and eventual heart failure. Tissue engineering and regenerative medicine principles provide an alternative approach to restoring myocardial function by designing constructs that will restore the mechanical function of the heart. In this review, we will describe the cellular events that take place after an MI and describe current treatments. We will also describe how biomaterials, alone or in combination with a cellular component, have been used to engineer suitable myocardium replacement constructs and how new advanced culture systems will be required to achieve clinical success.

Obesity and Heart Failure as a Mediator of the Cerebrorenal Interaction

OpenAIRE

Jindal, Ankur; Whaley-Connell, Adam; Sowers, James R.

2013-01-01

The obesity epidemic is contributing substantially to the burden of cardiovascular disease including heart disease and congestive heart failure, in the United States and the rest of the world. Overnutrition as a driver of obesity, promotes alterations in fatty acid, lipid, and glucose metabolism that influence myocardial function and progression of heart failure from diastolic to systolic failure. The association of progressive heart failure and progressive chronic kidney disease is well docu...

Hypertension as a risk factor for heart failure.

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Kannan, Arun; Janardhanan, Rajesh

2014-07-01

Hypertension remains a significant risk factor for development of congestive heart failure CHF), with various mechanisms contributing to both systolic and diastolic dysfunction. The pathogenesis of myocardial changes includes structural remodeling, left ventricular hypertrophy, and fibrosis. Activation of the sympathetic nervous system and renin-angiotensin system is a key contributing factor of hypertension, and thus interventions that antagonize these systems promote regression of hypertrophy and heart failure. Control of blood pressure is of paramount importance in improving the prognosis of patients with heart failure.

Effect of ionizing radiations on connective tissue

International Nuclear Information System (INIS)

Altman, K.I.; Gerber, G.B.

1980-01-01

The effects of ionizing radiations on connective tissue in lung, heart, vasculature, kidney, skin, and skeletal tissues are reviewed. Special emphasis is given to the effect of ionizing radiations on vasculo-connective tissue and fibrotic changes following radiation-induced injury to organs and tissues. In order to put the subject matter in proper prospective, the general biochemistry, physiology, and pathology of connective tissue is reviewed briefly together with the participation of connective tissue in disease. The review closes with an assessment of future problems and an enumeration and discussion of important, as yet unanswered questions

Fluid mechanics of heart valves.

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Yoganathan, Ajit P; He, Zhaoming; Casey Jones, S

2004-01-01

Valvular heart disease is a life-threatening disease that afflicts millions of people worldwide and leads to approximately 250,000 valve repairs and/or replacements each year. Malfunction of a native valve impairs its efficient fluid mechanic/hemodynamic performance. Artificial heart valves have been used since 1960 to replace diseased native valves and have saved millions of lives. Unfortunately, despite four decades of use, these devices are less than ideal and lead to many complications. Many of these complications/problems are directly related to the fluid mechanics associated with the various mechanical and bioprosthetic valve designs. This review focuses on the state-of-the-art experimental and computational fluid mechanics of native and prosthetic heart valves in current clinical use. The fluid dynamic performance characteristics of caged-ball, tilting-disc, bileaflet mechanical valves and porcine and pericardial stented and nonstented bioprostheic valves are reviewed. Other issues related to heart valve performance, such as biomaterials, solid mechanics, tissue mechanics, and durability, are not addressed in this review.

Toll-Like Receptor 9 Promotes Cardiac Inflammation and Heart Failure during Polymicrobial Sepsis

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Ralph Lohner

2013-01-01

Full Text Available Background. Aim was to elucidate the role of toll-like receptor 9 (TLR9 in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. Methods. Sepsis was induced via colon ascendens stent peritonitis (CASP in C57BL/6 wild-type (WT and TLR9-deficient (TLR9-D mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. Results. CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. Conclusions. In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.

Differential tissue expression of enhanced green fluorescent protein in 'green mice'.

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Ma, De-Fu; Tezuka, Hideo; Kondo, Tetsuo; Sudo, Katsuko; Niu, Dong-Feng; Nakazawa, Tadao; Kawasaki, Tomonori; Yamane, Tetsu; Nakamura, Nobuki; Katoh, Ryohei

2010-06-01

In order to clarify tissue expression of enhanced green fluorescent protein (EGFP) in 'green mice' from a transgenic line having an EGFP cDNA under the control of a chicken beta-actin promoter and cytomegalovirus enhancer, we studied the expression of EGFP in various organs and tissues from these 'green mice' by immunohistochemistry with anti- EGFP antibody in conjunction with direct observation for EGFP fluorescence using confocal laser scanning microscopy. On immunohistochemical examination and on direct observation by confocal laser scanning microscopy, the level of EGFP expression varied among organs and tissues. EGFP expression was diffusely and strongly observed in the skin, pituitary, thyroid gland, parathyroid gland, heart, gall bladder, pancreas, adrenals and urinary bladder. There was only sporadic and weak expression of EGFP in the epithelium of the trachea, bronchus of the lung, stratified squamous epithelium and gastric glands of the stomach, hepatic bile ducts of the liver, glomeruli and renal tubules of the kidney and endo-metrial glands of the uterus. Furthermore, EGFP was only demonstrated within the goblet and paneth cells in the colon and small intestine, the tall columnar cells in the ductus epididymis, and the leydig cells in the testis. In conclusion, our results show that EGFP is differentially expressed in organs and tissues of 'green mice', which indicates that 'green mice' may prove useful for research involving transplantation and tissue clonality.

Stem cell therapy for ischemic heart diseases.

Science.gov (United States)

Yu, Hong; Lu, Kai; Zhu, Jinyun; Wang, Jian'an

2017-01-01

Ischemic heart diseases, especially the myocardial infarction, is a major hazard problem to human health. Despite substantial advances in control of risk factors and therapies with drugs and interventions including bypass surgery and stent placement, the ischemic heart diseases usually result in heart failure (HF), which could aggravate social burden and increase the mortality rate. The current therapeutic methods to treat HF stay at delaying the disease progression without repair and regeneration of the damaged myocardium. While heart transplantation is the only effective therapy for end-stage patients, limited supply of donor heart makes it impossible to meet the substantial demand from patients with HF. Stem cell-based transplantation is one of the most promising treatment for the damaged myocardial tissue. Key recent published literatures and ClinicalTrials.gov. Stem cell-based therapy is a promising strategy for the damaged myocardial tissue. Different kinds of stem cells have their advantages for treatment of Ischemic heart diseases. The efficacy and potency of cell therapies vary significantly from trial to trial; some clinical trials did not show benefit. Diverged effects of cell therapy could be affected by cell types, sources, delivery methods, dose and their mechanisms by which delivered cells exert their effects. Understanding the origin of the regenerated cardiomyocytes, exploring the therapeutic effects of stem cell-derived exosomes and using the cell reprogram technology to improve the efficacy of cell therapy for cardiovascular diseases. Recently, stem cell-derived exosomes emerge as a critical player in paracrine mechanism of stem cell-based therapy. It is promising to exploit exosomes-based cell-free therapy for ischemic heart diseases in the future. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Environmental regulation of valvulogenesis:implications for tissue engineering

NARCIS (Netherlands)

Riem Vis, P.W.; Kluin, J.; Sluijter, J.P.G.; Herwerden, van L.A.; Bouten, C.V.C.

2011-01-01

Ongoing research efforts aim at improving the creation of tissue-engineered heart valves for in vivo systemic application. Hence, in vitro studies concentrate on optimising culture protocols incorporating biological as well as biophysical stimuli for tissue development. Important lessons can be

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors.

Science.gov (United States)

Butler, Jason M; Kobayashi, Hideki; Rafii, Shahin

2010-02-01

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

Tissue motion in blood velocity estimation and its simulation

DEFF Research Database (Denmark)

Schlaikjer, Malene; Torp-Pedersen, Søren; Jensen, Jørgen Arendt

1998-01-01

to the improvement of color flow imaging. Optimization based on in-vivo data is difficult since the blood and tissue signals cannot be accurately distinguished and the correct extend of the vessel under investigation is often unknown. This study introduces a model for the simulation of blood velocity data in which...... tissue motion is included. Tissue motion from breathing, heart beat, and vessel pulsation were determined based on in-vivo RF-data obtained from 10 healthy volunteers. The measurements were taken at the carotid artery at one condition and in the liver at three conditions. Each measurement was repeated 10....... The motion due to the heart, when the volunteer was asked to hold his breath, gave a peak velocity of 4.2±1.7 mm/s. The movement of the carotid artery wall due to changing blood pressure had a peak velocity of 8.9±3.7 mm/s over the cardiac cycle. The variations are due to differences in heart rhythm...

Heart Failure as an Aging-Related Phenotype.

Science.gov (United States)

Morita, Hiroyuki; Komuro, Issei

2018-01-27

The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

Evaluating the effectiveness of psychosocial resilience training for heart health, and the added value of promoting physical activity: a cluster randomized trial of the READY program

Directory of Open Access Journals (Sweden)

Pakenham Kenneth I

2009-11-01

Full Text Available Abstract Background Depression and poor social support are significant risk factors for coronary heart disease (CHD, and stress and anxiety can trigger coronary events. People experiencing such psychosocial difficulties are more likely to be physically inactive, which is also an independent risk factor for CHD. Resilience training can target these risk factors, but there is little research evaluating the effectiveness of such programs. This paper describes the design and measures of a study to evaluate a resilience training program (READY to promote psychosocial well-being for heart health, and the added value of integrating physical activity promotion. Methods/Design In a cluster randomized trial, 95 participants will be allocated to either a waitlist or one of two intervention conditions. Both intervention conditions will receive a 10 × 2.5 hour group resilience training program (READY over 13 weeks. The program targets five protective factors identified from empirical evidence and analyzed as mediating variables: positive emotions, cognitive flexibility, social support, life meaning, and active coping. Resilience enhancement strategies reflect the six core Acceptance and Commitment Therapy processes (values, mindfulness, defusion, acceptance, self-as-context, committed action and Cognitive Behavior Therapy strategies such as relaxation training and social support building skills. Sessions include psychoeducation, discussions, experiential exercises, and home assignments. One intervention condition will include an additional session and ongoing content promoting physical activity. Measurement will occur at baseline, two weeks post intervention, and at eight weeks follow-up, and will include questionnaires, pedometer step logs, and physical and hematological measures. Primary outcome measures will include self-reported indicators of psychosocial well-being and depression. Secondary outcome measures will include self-reported indicators of

Heart disease and gender in mass print media.

Science.gov (United States)

Clarke, Juanne

2010-03-01

Heart disease is a major cause of death, disease and disability in the developed world for both men and women. Women appear to be under-diagnosed and treated both because they fail to visit the doctor or hospital with relevant symptoms and because doctors tend to dismiss the seriousness of women's symptoms of heart disease. This review examined the way that popular mass print media present the possible association between gender and heart disease. It found that there was: [1] an under-representation of heart disease as a possible concern to women, [2] a dismissing or sensationalization of women's heart disease, [3] a tendency to blame women's complex menopausal bodies for the causes of heart disease, [4] an association of women with the heart disease of their husbands, [5] a linking of heart disease with masculinity and [6] a promotion of the idea of the need for women to fear of heart disease and the necessity of taking cholesterol-lowering drugs. The review concluded with suggestions for further research and for practice. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Myocardial regeneration potential of adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

2010-10-22

Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

Myocardial regeneration potential of adipose tissue-derived stem cells

International Nuclear Information System (INIS)

Bai, Xiaowen; Alt, Eckhard

2010-01-01

Research highlights: → Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. → For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. → This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying

Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

Science.gov (United States)

Heart failure (HF) is defined primarily by the impairment of cardiac function and consequent inability of the heart to supply tissues with ample oxygen. To study HF etiology, investigators have applied many different techniques to elicit this condition in animals, with varying de...

Congenital heart disease protein 5 associates with CASZ1 to maintain myocardial tissue integrity.

Science.gov (United States)

Sojka, Stephen; Amin, Nirav M; Gibbs, Devin; Christine, Kathleen S; Charpentier, Marta S; Conlon, Frank L

2014-08-01

The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development. © 2014. Published by The Company of Biologists Ltd.

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

Science.gov (United States)

Gourdie, Robert G.; Dimmeler, Stefanie; Kohl, Peter

2016-01-01

Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development. PMID:27339799

Clinical research on the expression of Lgr5 in the colon cancer tissues and its transfer promoting role

Directory of Open Access Journals (Sweden)

Xin-Jun Shu

2016-05-01

Full Text Available Objective: To detect the expression of Lgr5 in the colon cancer tissue, and to explore its correlation with the clinical and pathological characteristics and its role in promoting the tumor invasion and metastasis. Methods: A total of 102 specimens from the patients with colon cancer who were admitted in the General Surgery Department of our hospital for resection from April, 2013 to October, 2015 were included in the study; meanwhile, 35 colorectal adenoma specimens, and 137 normal colon tissue specimens were collected. The immunohistochemical method was used to detect the expression of Lgr5. Results: The positive rate of Lgr5 in the colon cancer tissues (62.75% was significantly higher than that in the adenoma tissues (28.57% and normal tissues (16.06%. The positive expression of Lgr5 in the colon cancer tissues was associated with the adenocarcinoma differentiation degree, Dukes staging, lymphatic metastasis, and distant metastasis. Meanwhile, it was found by the Logistic regression that the adenocarcinoma differentiation degree, lymphatic metastasis, and distant metastasis were the independent predictive factors for the positive expression of Lgr5. Conclusions: The increasement of Lgr5 expression is probably involved in the formation, differentiation, invasion, and metastasis of colon cancer; therefore, Lgr5 is expected to be a new therapeutic target aiming at colon cancer stem cells.

The pathophysiology of heart failure.

Science.gov (United States)

Kemp, Clinton D; Conte, John V

2012-01-01

Heart failure is a clinical syndrome that results when the heart is unable to provide sufficient blood flow to meet metabolic requirements or accommodate systemic venous return. This common condition affects over 5 million people in the United States at a cost of $10-38 billion per year. Heart failure results from injury to the myocardium from a variety of causes including ischemic heart disease, hypertension, and diabetes. Less common etiologies include cardiomyopathies, valvular disease, myocarditis, infections, systemic toxins, and cardiotoxic drugs. As the heart fails, patients develop symptoms which include dyspnea from pulmonary congestion, and peripheral edema and ascites from impaired venous return. Constitutional symptoms such as nausea, lack of appetite, and fatigue are also common. There are several compensatory mechanisms that occur as the failing heart attempts to maintain adequate function. These include increasing cardiac output via the Frank-Starling mechanism, increasing ventricular volume and wall thickness through ventricular remodeling, and maintaining tissue perfusion with augmented mean arterial pressure through activation of neurohormonal systems. Although initially beneficial in the early stages of heart failure, all of these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Treatment strategies have been developed based upon the understanding of these compensatory mechanisms. Medical therapy includes diuresis, suppression of the overactive neurohormonal systems, and augmentation of contractility. Surgical options include ventricular resynchronization therapy, surgical ventricular remodeling, ventricular assist device implantation, and heart transplantation. Despite significant understanding of the underlying pathophysiological mechanisms in heart failure, this disease causes significant morbidity and carries a 50% 5-year mortality. Copyright © 2012 Elsevier Inc. All rights reserved.

DGAT1 Expression Increases Heart Triglyceride Content but Ameliorates Lipotoxicity*

OpenAIRE

Liu, Li; Shi, XiaoJing; Bharadwaj, Kalyani G.; Ikeda, Shota; Yamashita, Haruyo; Yagyu, Hiroaki; Schaffer, Jean E.; Yu, Yi-Hao; Goldberg, Ira J.

2009-01-01

Intracellular lipid accumulation in the heart is associated with cardiomyopathy, yet the precise role of triglyceride (TG) remains unclear. With exercise, wild type hearts develop physiologic hypertrophy. This was associated with greater TG stores and a marked induction of the TG-synthesizing enzyme diacylglycerol (DAG) acyltransferase 1 (DGAT1). Transgenic overexpression of DGAT1 in the heart using the cardiomyocyte- specific α-myosin heavy chain (MHC) promoter led to approximately a doublin...

Development of measures of organizational leadership for health promotion.

Science.gov (United States)

Barrett, Linda; Plotnikoff, Ronald C; Raine, Kim; Anderson, Donna

2005-04-01

This study describes the development and psychometric evaluation of four scales measuring leadership for health promotion at an organizational level in the baseline survey (n=144) of the Alberta Heart Health Project. Content validity was established through a series of focus groups and expert opinion appraisals, pilot testing of a draft based on capacity assessment instruments developed by other provinces involved in the Canadian Heart Health Initiative, and the literature. Psychometric analyses provided empirical evidence of the construct validity and reliability of the organizational leadership scales. Principal component analysis verified the unidimensionality of the leadership scales of (a) Practices for Organizational Learning, (b) Wellness Planning, (c) Workplace Climate, and (d) Organization Member Development. Scale alpha coefficients ranged between .79 and .91 thus establishing good to high scale internal consistencies. These measures can be used by both researchers and practitioners for the assessment of organizational leadership for health promotion and heart health promotion.

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

Science.gov (United States)

Salamon, Achim; van Vlierberghe, Sandra; van Nieuwenhove, Ine; Baudisch, Frank; Graulus, Geert-Jan; Benecke, Verena; Alberti, Kristin; Neumann, Hans-Georg; Rychly, Joachim; Martins, José C.; Dubruel, Peter; Peters, Kirsten

2014-01-01

Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies. PMID:28788517

Evaluation of shrinkage temperature of bovine pericardium tissue for bioprosthetic heart valve application by differential scanning calorimetry and freeze-drying microscopy

Directory of Open Access Journals (Sweden)

Virgilio Tattini Jr

2007-03-01

Full Text Available Bovine pericardium bioprosthesis has become a commonly accepted device for heart valve replacement. Present practice relies on the measurement of shrinkage temperature, observed as a dramatic shortening of tissue length. Several reports in the last decade have utilized differential scanning calorimetry (DSC as an alternative method to determine the shrinkage temperature, which is accompanied by the absorption of heat, giving rise to an endothermic peak over the shrinkage temperature range of biological tissues. Usually, freeze-drying microscope is used to determine collapse temperature during the lyophilization of solutions. On this experiment we used this technique to study the shrinkage event. The aim of this work was to compare the results of shrinkage temperature obtained by DSC with the results obtained by freeze-drying microscopy. The results showed that both techniques provided excellent sensitivity and reproducibility, and gave information on the thermal shrinkage transition via the thermodynamical parameters inherent of each method.

Segmentation of multiple heart cavities in 3-D transesophageal ultrasound images.

Science.gov (United States)

Haak, Alexander; Vegas-Sánchez-Ferrero, Gonzalo; Mulder, Harriët W; Ren, Ben; Kirişli, Hortense A; Metz, Coert; van Burken, Gerard; van Stralen, Marijn; Pluim, Josien P W; van der Steen, Antonius F W; van Walsum, Theo; Bosch, Johannes G

2015-06-01

Three-dimensional transesophageal echocardiography (TEE) is an excellent modality for real-time visualization of the heart and monitoring of interventions. To improve the usability of 3-D TEE for intervention monitoring and catheter guidance, automated segmentation is desired. However, 3-D TEE segmentation is still a challenging task due to the complex anatomy with multiple cavities, the limited TEE field of view, and typical ultrasound artifacts. We propose to segment all cavities within the TEE view with a multi-cavity active shape model (ASM) in conjunction with a tissue/blood classification based on a gamma mixture model (GMM). 3-D TEE image data of twenty patients were acquired with a Philips X7-2t matrix TEE probe. Tissue probability maps were estimated by a two-class (blood/tissue) GMM. A statistical shape model containing the left ventricle, right ventricle, left atrium, right atrium, and aorta was derived from computed tomography angiography (CTA) segmentations by principal component analysis. ASMs of the whole heart and individual cavities were generated and consecutively fitted to tissue probability maps. First, an average whole-heart model was aligned with the 3-D TEE based on three manually indicated anatomical landmarks. Second, pose and shape of the whole-heart ASM were fitted by a weighted update scheme excluding parts outside of the image sector. Third, pose and shape of ASM for individual heart cavities were initialized by the previous whole heart ASM and updated in a regularized manner to fit the tissue probability maps. The ASM segmentations were validated against manual outlines by two observers and CTA derived segmentations. Dice coefficients and point-to-surface distances were used to determine segmentation accuracy. ASM segmentations were successful in 19 of 20 cases. The median Dice coefficient for all successful segmentations versus the average observer ranged from 90% to 71% compared with an inter-observer range of 95% to 84%. The

Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

Science.gov (United States)

Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

2017-02-02

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development. Copyright © 2017 Elsevier Inc. All rights reserved.

Total artificial heart implantation for biventricular failure due to eosinophilic myocarditis.

Science.gov (United States)

Kawabori, Masashi; Kurihara, Chitaru; Miller, Yair; Heck, Kent A; Bogaev, Roberta C; Civitello, Andrew B; Cohn, William E; Frazier, O H; Morgan, Jeffrey A

2017-09-01

Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

The histopathologic reliability of tissue taken from cadavers within the gross anatomy laboratory.

Science.gov (United States)

Rae, Guenevere; Newman, William P; McGoey, Robin; Donthamsetty, Supriya; Karpinski, Aryn C; Green, Jeffrey

2018-03-01

The purpose of this study was to examine the histopathologic reliability of embalmed cadaveric tissue taken from the gross anatomy laboratory. Tissue samples from hearts, livers, lungs, and kidneys were collected after the medical students' dissection course was completed. All of the cadavers were embalmed in a formalin-based fixative solution. The tissue was processed, embedded in paraffin, sectioned at six micrometers, and stained with H&E. The microscope slides were evaluated by a board certified pathologist to determine whether the cellular components of the tissues were preserved at a high enough quality to allow for histopathologic diagnosis. There was a statistically significant relationship between ratings and organ groups. Across all organs, there was a smaller proportion of "poor" ratings. The lung group had the highest percentage of "poor" ratings (23.1%). The heart group had the least "poor" ratings (0.0%). The largest percentage of "satisfactory" ratings were in the lung group (52.8%), and the heart group contained the highest percentage of "good" ratings (58.5%) The lung group had the lowest percentage of "good" ratings (24.2%). These results indicate that heart tissue is more reliable than lung, kidney, or liver tissue when utilizing tissue from the gross anatomy laboratory for research and/or educational purposes. This information advises educators and researchers about the quality and histopathologic reliability of tissue samples obtained from the gross anatomy laboratory. Anat Sci Educ 11: 207-214. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Differential Lectin Binding Patterns Identify Distinct Heart Regions in Giant Danio (Devario aequipinnatus) and Zebrafish (Danio rerio) Hearts

Science.gov (United States)

Manalo, Trina; May, Adam; Quinn, Joshua; Lafontant, Dominique S.; Shifatu, Olubusola; He, Wei; Gonzalez-Rosa, Juan M.; Burns, Geoffrey C.; Burns, Caroline E.; Burns, Alan R.; Lafontant, Pascal J.

2016-01-01

Lectins are carbohydrate-binding proteins commonly used as biochemical and histochemical tools to study glycoconjugate (glycoproteins, glycolipids) expression patterns in cells, tissues, including mammalian hearts. However, lectins have received little attention in zebrafish (Danio rerio) and giant danio (Devario aequipinnatus) heart studies. Here, we sought to determine the binding patterns of six commonly used lectins—wheat germ agglutinin (WGA), Ulex europaeus agglutinin, Bandeiraea simplicifolia lectin (BS lectin), concanavalin A (Con A), Ricinus communis agglutinin I (RCA I), and Lycopersicon esculentum agglutinin (tomato lectin)—in these hearts. Con A showed broad staining in the myocardium. WGA stained cardiac myocyte borders, with binding markedly stronger in the compact heart and bulbus. BS lectin, which stained giant danio coronaries, was used to measure vascular reconstruction during regeneration. However, BS lectin reacted poorly in zebrafish. RCA I stained the compact heart of both fish. Tomato lectin stained the giant danio, and while low reactivity was seen in the zebrafish ventricle, staining was observed in their transitional cardiac myocytes. In addition, we observed unique staining patterns in the developing zebrafish heart. Lectins’ ability to reveal differential glycoconjugate expression in giant danio and zebrafish hearts suggests they can serve as simple but important tools in studies of developing, adult, and regenerating fish hearts. PMID:27680670

Biochemical Study of Oxidative Stress Markers in the Liver, Kidney and Heart of High Fat Diet Induced Obesity in Rats

Directory of Open Access Journals (Sweden)

Noeman Saad A

2011-08-01

Full Text Available Abstract Background Obesity has become a leading global health problem owing to its strong association with a high incidence of diseases. Aim To induce rat obesity using high fat diet (HFD and to estimate oxidative stress markers in their liver, heart and kidney tissues in order to shed the light on the effect of obesity on these organs. Materials and methods Sixty white albino rats weighing 150-200 g were randomly divided into two equal groups; group I: received high fat diet for 16 weeks, and group II (control group: received only normal diet (rat chow for 16 weeks. Blood samples were taken for measurement of lipid profile, tissue samples from liver, heart and kidney were taken for determination of malondialdehyde (MDA, protein carbonyl (PCO, reduced glutathione (GSH levels, and the activities of glutathione S- transferase (GST glutathione peroxidase (GPx, catalase (CAT and paraoxonase1 (PON1 enzymes. Results Data showed that feeding HFD diet significantly increased final body weight and induced a state of dyslipideamia. Also our results showed a significant increase MDA and PCO levels in the hepatic, heart and renal tissues of obese rats, as well as a significant decrease in the activity of GST, GPx and PON 1 enzymes. On the other hand CAT enzyme activity showed significant decrease only in renal tissues of obese rats with non significant difference in hepatic and heart tissues. GSH levels showed significant decrease in both renal and hepatic tissues of obese animals and significant increase in their heart tissues. Correlation studies in obese animals showed a negative correlation between MDA and PCO tissue levels and the activities of GPx, GST and PON1 in all tissues and also with CAT enzyme activity in renal tissues. Also a negative correlation was detected between MDA & PCO tissues levels and GSH levels in both hepatic and renal tissues. While positive correlation was found between them and GSH levels in heart tissues. Conclusion High fat

The canonical way to make a heart: β-catenin and plakoglobin in heart development and remodeling.

Science.gov (United States)

Piven, Oksana O; Winata, Cecilia L

2017-12-01

The main mediator of the canonical Wnt pathway, β-catenin, is a major effector of embryonic development, postnatal tissue homeostasis, and adult tissue regeneration. The requirement for β-catenin in cardiogenesis and embryogenesis has been well established. However, many questions regarding the molecular mechanisms by which β-catenin and canonical Wnt signaling regulate these developmental processes remain unanswered. An interesting question that emerged from our studies concerns how β-catenin signaling is modulated through interaction with other factors. Recent experimental data implicate new players in canonical Wnt signaling, particularly those which modulate β-catenin function in many its biological processes, including cardiogenesis. One of the interesting candidates is plakoglobin, a little-studied member of the catenin family which shares several mechanistic and functional features with its close relative, β-catenin. Here we have focused on the function of β-catenin in cardiogenesis. We also summarize findings on plakoglobin signaling function and discuss possible interplays between β-catenin and plakoglobin in the regulation of embryonic heart development. Impact statement Heart development, function, and remodeling are complex processes orchestrated by multiple signaling networks. This review examines our current knowledge of the role of canonical Wnt signaling in cardiogenesis and heart remodeling, focusing primarily on the mechanistic action of its effector β-catenin. We summarize the generally accepted understanding of the field based on experimental in vitro and in vivo data, and address unresolved questions in the field, specifically relating to the role of canonical Wnt signaling in heart maturation and regeneration. What are the modulators of canonical Wnt, and particularly what are the potential roles of plakoglobin, a close relative of β-catenin, in regulating Wnt signaling?Answers to these questions will enhance our understanding of the

Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

Science.gov (United States)

Jones, D R; Hoffmann, S C; Sellars, M; Egan, T M

1997-05-01

Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease

Directory of Open Access Journals (Sweden)

Brian Murphy

2013-08-01

Full Text Available Caprine arthritis encephalitis virus (CAEV is a lentivirus that infects both goats and sheep and is closely related to maedi-visna virus that infects sheep; collectively, these viruses are known as small ruminant lentiviruses (SRLV. Infection of goats and sheep with SRLV typically results in discrete inflammatory diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV-infected animals concurrently demonstrating lentivirus-associated lesions in tissues of lung, mammary gland, joint synovium and the central nervous system are either very rare or have not been reported. Here we describe a novel CAEV promoter isolated from a sheep with multisystemic lentivirus-associated inflammatory disease including interstitial pneumonia, mastitis, polyarthritis and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from five different anatomical locations (brain stem, spinal cord, lung, mammary gland and carpal joint synovium, all of which demonstrated lesions characteristic of lentivirus associated inflammation. This SRLV promoter isolate was found to be closely related to CAEV promoters isolated from goats in northern California and other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic disease; the stability of the transcription factor binding sites within the U3 promoter sequence are discussed.

Noninvasive Measurement of EKG Properties of 3D Artificial Heart Muscle

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Betsy H. Salazar

2017-06-01

Full Text Available Developing and testing a custom fabricated 16-electrode noninvasive direct contact system was necessary to assess the electrical properties of bioengineered heart muscle and to further evaluate the efficacy of cardiac constructs. By culturing neonatal rat primary cardiac cells on a fibrin gel, we constructed 3D artificial heart muscle (3D-AHM, as described in previous studies, which were used in validating this novel system. Electrical and mechanical functional assessment of the tissues was performed, which yielded contractile forces of the tissues, electrical field potential characteristics, and tissue conduction velocities (CV (20–170 cm/s. Immunohistological evaluation revealed the formation of cardiac tissue structures and cardiomyocyte proliferation. EKG data analysis also yielded time delays between signals in the range of 0–38 ms with electrical maps showing some evidence of synchronous contraction within the fabricated tissues. This study demonstrates the effectiveness and practicality of our novel EKG measuring system to acquire distinct electrical metrics of 3D-AHM, which will aid in increasing the viability and applicability of cardiac tissue constructs.

Occupational Health Services Plans to Make February a Healthy, Heart-y Month | Poster

Science.gov (United States)

In celebration of American Heart Month this February, Occupational Health Services is hosting multiple events to promote heart health and raise awareness about heart disease and its associated risks. American Heart Month kicks off on Monday, January 29, when staff will be sponsoring a table outside of the 15th Annual Protective Services Chili Cookoff and holding a raffle for free gym bags to encourage employees to stay active.

Persufflation (gaseous oxygen perfusion) as a method of heart preservation.

Science.gov (United States)

Suszynski, Thomas M; Rizzari, Michael D; Scott, William E; Eckman, Peter M; Fonger, James D; John, Ranjit; Chronos, Nicolas; Tempelman, Linda A; Sutherland, David E R; Papas, Klearchos K

2013-04-22

Persufflation (PSF; gaseous oxygen perfusion) is an organ preservation technique with a potential for use in donor heart preservation. Improved heart preservation with PSF may improve outcomes by maintaining cardiac tissue quality in the setting of longer cold ischemia times and possibly increasing the number of donor hearts available for allotransplant. Published data suggests that PSF is able to extend the cold storage times for porcine hearts up to 14 hours without compromising viability and function, and has been shown to resuscitate porcine hearts following donation after cardiac death. This review summarizes key published work on heart PSF, including prospective implications and future directions for PSF in heart transplantation. We emphasize the potential impact of extending preservation times and expanding donor selection criteria in heart allotransplant. Additionally, the key issues that need to be addressed before PSF were to become a widely utilized preservation strategy prior to clinical heart transplantation are summarized and discussed.

Electrodes as social glue: measuring heart rate promotes giving in the trust game.

Science.gov (United States)

Van Lange, Paul A M; Finkenauer, Catrin; Popma, Arne; van Vugt, Mark

2011-06-01

While physiological measures are increasingly used to help us understand the workings of interpersonal trust (and related behaviors), we know very little about the effects of such measures on trust. We examined the effects of a classic measure, the measurement of heart rate using a standard protocol, on behavioral trust in dyads of women who did not know each other. Behavioral trust was assessed in the trust game, in which the trustor decides how much money from their subject payment to give to a trustee, while knowing that the experimenter triples that amount before giving it to the trustee, after which the trustee decides how much money to return to the trustor. As predicted, we found greater levels of behavioral trust in the trust game, as well as greater returns by the trustees (which were accounted for by trustor's giving), in the heart rate (HR) than in no heart rate (NHR) measurement condition. Parallel findings were observed for self-reported trust. Findings are discussed in terms of the idea that the elusive effects of a protocol for measuring heart rate can cause pronounced effects on subsequent social interactions via enhanced interpersonal trust. 2011 Elsevier B.V. All rights reserved.

Fluorine-18 heart dosimetry in myocardial perfusion imaging

Energy Technology Data Exchange (ETDEWEB)

Toledo, Janine M.; Trindade, Bruno; Campos, Tarcísio P.R., E-mail: janine.toledo@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Programa de Pós-Graduação em Ciências e Técnicas Nucleares

2017-07-01

This paper conducts a recalling in myocardial perfusion imaging (MPI) followed by a spatial dosimetric investigation of the Fluorine-18 distributed at the myocardium by self-absorption of the heart uptake. Methods and Results: Radiological data manipulation was prepared and a computational heart voxelized model was assembled. A set of images from the abdominal aorta and angiotomography of the thorax was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of fluorine-18 was assumed into the heart myocardial wall. MCNP – Monte Carlo Code was used to provide the photon transport into the heart model taken in consideration the interactions into the tissues. The spatial dose distribution and histogram dose versus volume are presented. An analytical alternative model was addressed to the data validation. The present developed tools can produce spatial dose distribution in MPI at heart. Specially, the dosimetry performed elucidates imparted dose in the myocardial muscle per unit of injected Fluorine-18 activity by self-absorption of the heart uptake, which can contribute to future deterministic effect investigations. (author)

Fluorine-18 heart dosimetry in myocardial perfusion imaging

International Nuclear Information System (INIS)

Toledo, Janine M.; Trindade, Bruno; Campos, Tarcísio P.R.

2017-01-01

This paper conducts a recalling in myocardial perfusion imaging (MPI) followed by a spatial dosimetric investigation of the Fluorine-18 distributed at the myocardium by self-absorption of the heart uptake. Methods and Results: Radiological data manipulation was prepared and a computational heart voxelized model was assembled. A set of images from the abdominal aorta and angiotomography of the thorax was set up providing anatomic and functional information for heart modeling in SISCODES code. A homogeneous distribution of fluorine-18 was assumed into the heart myocardial wall. MCNP – Monte Carlo Code was used to provide the photon transport into the heart model taken in consideration the interactions into the tissues. The spatial dose distribution and histogram dose versus volume are presented. An analytical alternative model was addressed to the data validation. The present developed tools can produce spatial dose distribution in MPI at heart. Specially, the dosimetry performed elucidates imparted dose in the myocardial muscle per unit of injected Fluorine-18 activity by self-absorption of the heart uptake, which can contribute to future deterministic effect investigations. (author)

Preliminary Examination of X-ray Scattering from Human Tissues

International Nuclear Information System (INIS)

Desouky, O.S.; Wilkinson, S.; Hall, C.; Rogers, K.; Round, A.

2008-01-01

Small Angle x-ray scattering (SAXS) and wide angle x-ray scattering (WAXS) patterns have been recorded from different human soft tissues using x-ray synchrotron radiation.Pathological breast, normal kidney and lung tissues show SAXS peaks at q-values equal to 0.291 nm -1 and 0.481 nm -1 (d 21.6 nm and d =13. nm) which are the 3 r d and 5 t h order of the well known axial D-spacing of collagen fibrils. The diffraction is particularly intense in the meridional direction indicating some febrile alignment. In contrast, the normal tissue of brain, liver and heart shows diffuse scatter.The wide-angle coherent scattering from normal human tissues of brain, liver, heart, lung, and kidney is typical of that for amorphous materials. The scatter of the healthy adipose breast tissue shows a sharp peak at momentum transfer 1.24 nm -1 (d= 0.417 nm). The data of the other tissues appears to consist of a broad scattering peak. The two scattering regimes succeed in differentiating between the two major components of breast tissue, collagen and adipose tissue. The results of this study suggest that the soft tissues may have scattering patterns that are characteristics for the particular tissue types and tissue disease state. These results indicate that it may be possible use the coherent scattering as a diagnostic tool

Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance

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Nathan L. Price

2018-02-01

Full Text Available While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature of miRNAs raises concern over detrimental off-target effects. miR-33 has emerged as a likely target for treatment of cardiovascular diseases. However, the deleterious effects of long-term anti-miR-33 therapies and predisposition of miR-33−/− mice to obesity and metabolic dysfunction exemplify the possible pitfalls of miRNA-based therapies. Our work provides an in-depth characterization of miR-33−/− mice and explores the mechanisms by which loss of miR-33 promotes insulin resistance in key metabolic tissues. Contrary to previous reports, our data do not support a direct role for SREBP-1-mediated lipid synthesis in promoting these effects. Alternatively, in adipose tissue of miR-33−/− mice, we observe increased pre-adipocyte proliferation, enhanced lipid uptake, and impaired lipolysis. Moreover, we demonstrate that the driving force behind these abnormalities is increased food intake, which can be prevented by pair feeding with wild-type animals.

Gelatin-Based Hydrogels Promote Chondrogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells In Vitro

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Achim Salamon

2014-02-01

Full Text Available Due to the weak regeneration potential of cartilage, there is a high clinical incidence of articular joint disease, leading to a strong demand for cartilaginous tissue surrogates. The aim of this study was to evaluate a gelatin-based hydrogel for its suitability to support chondrogenic differentiation of human mesenchymal stem cells. Gelatin-based hydrogels are biodegradable, show high biocompatibility, and offer possibilities to introduce functional groups and/or ligands. In order to prove their chondrogenesis-supporting potential, a hydrogel film was developed and compared with standard cell culture polystyrene regarding the differentiation behavior of human mesenchymal stem cells. Cellular basis for this study were human adipose tissue-derived mesenchymal stem cells, which exhibit differentiation potential along the adipogenic, osteogenic and chondrogenic lineage. The results obtained show a promotive effect of gelatin-based hydrogels on chondrogenic differentiation of mesenchymal stem cells in vitro and therefore encourage subsequent in vivo studies.

Modeling and remodeling of the collagen architecture in cardiovascular tissues

NARCIS (Netherlands)

Driessen, N.J.B.

2006-01-01

Heart valve replacement by a mechanical or biological prosthesis represents a common surgical therapy for end-stage valvular heart diseases. A critical drawback of these prostheses is the inability to grow, repair and remodel in response to changes in the tissue’s environment. Tissue engineering

Congenital heart malformations induced by hemodynamic altering surgical interventions

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Madeline eMidgett

2014-08-01

Full Text Available Embryonic heart formation results from a dynamic interplay between genetic and environmental factors. Blood flow during early embryonic stages plays a critical role in heart development, as interactions between flow and cardiac tissues generate biomechanical forces that modulate cardiac growth and remodeling. Normal hemodynamic conditions are essential for proper cardiac development, while altered blood flow induced by surgical manipulations in animal models result in heart defects similar to those seen in humans with congenital heart disease. This review compares the altered hemodynamics, changes in tissue properties, and cardiac defects reported after common surgical interventions that alter hemodynamics in the early chick embryo, and shows that interventions produce a wide spectrum of cardiac defects. Vitelline vein ligation and left atrial ligation decrease blood pressure and flow; and outflow tract banding increases blood pressure and flow velocities. These three surgical interventions result in many of the same cardiac defects, which indicate that the altered hemodynamics interfere with common looping, septation and valve formation processes that occur after intervention and that shape the four-chambered heart. While many similar defects develop after the interventions, the varying degrees of hemodynamic load alteration among the three interventions also result in varying incidence and severity of cardiac defects, indicating that the hemodynamic modulation of cardiac developmental processes is strongly dependent on hemodynamic load.

Engineering Cardiac Muscle Tissue: A Maturating Field of Research.

Science.gov (United States)

Weinberger, Florian; Mannhardt, Ingra; Eschenhagen, Thomas

2017-04-28

Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair. © 2017 American Heart Association, Inc.

Towards a Tissue-Engineered Contractile Fontan-Conduit: The Fate of Cardiac Myocytes in the Subpulmonary Circulation.

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Daniel Biermann

Full Text Available The long-term outcome of patients with single ventricles improved over time, but remains poor compared to other congenital heart lesions with biventricular circulation. Main cause for this unfavourable outcome is the unphysiological hemodynamic of the Fontan circulation, such as subnormal systemic cardiac output and increased systemic-venous pressure. To overcome this limitation, we are developing the concept of a contractile extracardiac Fontan-tunnel. In this study, we evaluated the survival and structural development of a tissue-engineered conduit under in vivo conditions. Engineered heart tissue was generated from ventricular heart cells of neonatal Wistar rats, fibrinogen and thrombin. Engineered heart tissues started beating around day 8 in vitro and remained contractile in vivo throughout the experiment. After culture for 14 days constructs were implanted around the right superior vena cava of Wistar rats (n = 12. Animals were euthanized after 7, 14, 28 and 56 days postoperatively. Hematoxylin and eosin staining showed cardiomyocytes arranged in thick bundles within the engineered heart tissue-conduit. Immunostaining of sarcomeric actin, alpha-actin and connexin 43 revealed a well -developed cardiac myocyte structure. Magnetic resonance imaging (d14, n = 3 revealed no constriction or stenosis of the superior vena cava by the constructs. Engineered heart tissues survive and contract for extended periods after implantation around the superior vena cava of rats. Generation of larger constructs is warranted to evaluate functional benefits of a contractile Fontan-conduit.

Radioimmunoassay of bovine heart protein kinase

International Nuclear Information System (INIS)

Fleischer, N.; Rosen, O.M.; Reichlin, M.

1976-01-01

Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP : protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immunoreactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that cross reacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous

Magnesium Presence Prevents Removal of Antigenic Nuclear-Associated Proteins from Bovine Pericardium for Heart Valve Engineering.

Science.gov (United States)

Dalgliesh, Ailsa J; Liu, Zhi Zhao; Griffiths, Leigh G

2017-07-01

Current heart valve prostheses are associated with significant complications, including aggressive immune response, limited valve life expectancy, and inability to grow in juvenile patients. Animal derived "tissue" valves undergo glutaraldehyde fixation to mask tissue antigenicity; however, chronic immunological responses and associated calcification still commonly occur. A heart valve formed from an unfixed bovine pericardium (BP) extracellular matrix (ECM) scaffold, in which antigenic burden has been eliminated or significantly reduced, has potential to overcome deficiencies of current bioprostheses. Decellularization and antigen removal methods frequently use sequential solutions extrapolated from analytical chemistry approaches to promote solubility and removal of tissue components from resultant ECM scaffolds. However, the extent to which such prefractionation strategies may inhibit removal of antigenic tissue components has not been explored. We hypothesize that presence of magnesium in prefractionation steps causes DNA precipitation and reduces removal of nuclear-associated antigenic proteins. Keeping all variables consistent bar the addition or absence of magnesium (2 mM magnesium chloride hexahydrate), residual BP ECM scaffold antigenicity and removed antigenicity were assessed, along with residual and removed DNA content, ECM morphology, scaffold composition, and recellularization potential. Furthermore, we used proteomic methods to determine the mechanism by which magnesium presence or absence affects scaffold residual antigenicity. This study demonstrates that absence of magnesium from antigen removal solutions enhances solubility and subsequent removal of antigenic nuclear-associated proteins from BP. We therefore conclude that the primary mechanism of action for magnesium removal during antigen removal processes is avoidance of DNA precipitation, facilitating solubilization and removal of nuclear-associated antigenic proteins. Future studies are

"The Heart Truth:" Using the Power of Branding and Social Marketing to Increase Awareness of Heart Disease in Women.

Science.gov (United States)

Long, Terry; Taubenheim, Ann; Wayman, Jennifer; Temple, Sarah; Ruoff, Beth

2008-03-01

In September 2002, the National Heart, Lung, and Blood Institute launched The Heart Truth, the first federally-sponsored national campaign aimed at increasing awareness among women about their risk of heart disease. A traditional social marketing approach, including an extensive formative research phase, was used to plan, implement, and evaluate the campaign. With the creation of the Red Dress as the national symbol for women and heart disease awareness, the campaign integrated a branding strategy into its social marketing framework. The aim was to develop and promote a women's heart disease brand that would create a strong emotional connection with women. The Red Dress brand has had a powerful appeal to a wide diversity of women and has given momentum to the campaign's three-part implementation strategy of partnership development, media relations, and community action. In addition to generating its own substantial programming, The Heart Truth became a catalyst for a host of other national and local educational initiatives, both large and small. By the campaign's fifth anniversary, surveys showed that women were increasingly aware of heart disease as their leading cause of death and that the rise in awareness was associated with increased action to reduce heart disease risk.

Transcapillary permeability and subendothelial distribution of endothelial and amniotic fluid insulin-like growth factor binding proteins in the rat heart

International Nuclear Information System (INIS)

Bar, R.S.; Clemmons, D.R.; Boes, M.; Busby, W.H.; Booth, B.A.; Dake, B.L.; Sandra, A.

1990-01-01

Insulin-like growth factor (IGF) binding proteins (IGFBP) were purified from conditioned media of cultured bovine endothelial cells (ECBP) and from human amniotic fluid (IGFBP-1), and then labeled by radioiodination. 125I-ECBP and 125I-IGFBP-1 were perfused through isolated beating rat hearts for 1 and 5 min, and the hearts fixed and analyzed for 125I-BP content and distribution. One to 4% of the perfused 125I-ECBP and 125I-IGFBP-1 crossed the capillary boundary. The ECBPs predominantly localized as intact 125I-BP in connective tissue elements of the heart with less 125I-BP in cardiac muscle. The ratio of 125I-ECBP in connective tissue: muscle (normalized to percent vol of these compartments) was greater than or equal to 10:1. In contrast, the IGFBP-1 had a greater affinity for cardiac muscle with ratios of 125I-IGFBP-1 in connective tissue:muscle of approximately 1:2. When 125I-IGF-I, in the absence of any BPs, was perfused through the hearts approximately 3-5% left the microcirculation and was found in subendothelial tissues. 125I-IGF-I localized primarily to cardiac muscle with a distribution of connective tissue:cardiac muscle of about 1:3. The findings in the isolated perfused heart were confirmed in intact animals. After 125I-IGFBP-1 was injected into anesthetized rats and allowed to circulate for 5 min, substantial radioactivity was associated with the heart. As in the isolated heart, the IGFBP-1 preferentially localized to cardiac muscle with a connective tissue:cardiac muscle ratio of 1:3. We conclude that IGFBPs produced by endothelial cells and the IGFBP-1 contained in amniotic fluid can cross the capillary boundaries of the rat heart, and that the ECBPs preferentially localize in connective tissue elements of the myocardium, whereas IGFBP-1 predominantly localizes in cardiac muscle

CD133 antibody conjugation to decellularized human heart valves intended for circulating cell capture.

Science.gov (United States)

Vossler, John D; Min Ju, Young; Williams, J Koudy; Goldstein, Steven; Hamlin, James; Lee, Sang Jin; Yoo, James J; Atala, Anthony

2015-09-03

The long term efficacy of tissue based heart valve grafts may be limited by progressive degeneration characterized by immune mediated inflammation and calcification. To avoid this degeneration, decellularized heart valves with functionalized surfaces capable of rapid in vivo endothelialization have been developed. The aim of this study is to examine the capacity of CD133 antibody-conjugated valve tissue to capture circulating endothelial progenitor cells (EPCs). Decellularized human pulmonary valve tissue was conjugated with CD133 antibody at varying concentrations and exposed to CD133 expressing NTERA-2 cl.D1 (NT2) cells in a microflow chamber. The amount of CD133 antibody conjugated on the valve tissue surface and the number of NT2 cells captured in the presence of shear stress was measured. Both the amount of CD133 antibody conjugated to the valve leaflet surface and the number of adherent NT2 cells increased as the concentration of CD133 antibody present in the surface immobilization procedure increased. The data presented in this study support the hypothesis that the rate of CD133(+) cell adhesion in the presence of shear stress to decellularized heart valve tissue functionalized by CD133 antibody conjugation increases as the quantity of CD133 antibody conjugated to the tissue surface increases.

Changing Trend In Coronary Heart Disease In Nigeria

African Journals Online (AJOL)

Buchi

lifestyle. Conclusion: Coronary Heart disease is still relatively uncommon in ... the world where most health resources are channeled into .... cholesterol in the elderly population in Benin, Nigeria, .... Reducing risks, promoting healthy life.

Immunofluorescent histological studies of the role of fibronectin in the expression of the associative preferences of embryonic tissues.

Science.gov (United States)

Armstrong, P B; Armstrong, M T

1981-08-01

The identity of the chemical factors controlling the spreading behaviour of sheets of cells was examined in organ culture. When aggregates of two dissimilar tissues are apposed in organ culture, one tissue spreads reproducibly over the surface of the second. The present study employed indirect immunofluorescent localization techniques to evaluate the hypothesis that the spreading behaviour of chick embryonic heart tissue in culture is dominated by the presence or absence of the cell-surface and extracellular matrix protein fibronectin in the surface layers of the aggregates. Specifically, the hypothesis proposes that aggregates that display surface fibronectin earlier after culturing and/or in higher quantities segregate internally to aggregates that are slower to develop a surface layer of fibronectin or in which this layer contains reduced amounts of fibronectin. The hypothesis has been supported for 3 categories of behaviour of chick embryo heart tissue: (1) myocyte aggregates spread over myocyte aggregates containing a 20% admixture of heart fibroblasts, which in turn spread over heart fibroblast aggregates; (2) 5-day embryonic ventricle-tissue fragments maintained in culture for 0.5 days spread over ventricle fragments cultured for 2.5 days; and (3) 2-day embryonic ventricle spreads over 5-day ventricle. In all these situations, the aggregate type that segregates to an internal position displays more fibronectin at its surface than aggregate types that spread to occupy an external position. Evidence is presented that the fibronectin in heart tissue aggregates is elaborated by heart fibroblasts.

White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

Science.gov (United States)

Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

2010-01-01

The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

Directory of Open Access Journals (Sweden)

Götz Pilarczyk

2016-01-01

Full Text Available The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.

Dietary cholesterol, heart disease risk and cognitive dissonance.

Science.gov (United States)

McNamara, Donald J

2014-05-01

In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

Design Approaches to Myocardial and Vascular Tissue Engineering.

Science.gov (United States)

Akintewe, Olukemi O; Roberts, Erin G; Rim, Nae-Gyune; Ferguson, Michael A H; Wong, Joyce Y

2017-06-21

Engineered tissues represent an increasingly promising therapeutic approach for correcting structural defects and promoting tissue regeneration in cardiovascular diseases. One of the challenges associated with this approach has been the necessity for the replacement tissue to promote sufficient vascularization to maintain functionality after implantation. This review highlights a number of promising prevascularization design approaches for introducing vasculature into engineered tissues. Although we focus on encouraging blood vessel formation within myocardial implants, we also discuss techniques developed for other tissues that could eventually become relevant to engineered cardiac tissues. Because the ultimate solution to engineered tissue vascularization will require collaboration between wide-ranging disciplines such as developmental biology, tissue engineering, and computational modeling, we explore contributions from each field.

Anesthetic management of a 2-day-old with complete congenital heart block

Directory of Open Access Journals (Sweden)

Puneet Khanna

2014-01-01

Full Text Available Maternal connective tissue disorders such as Systemic Lupus Erythematosus (most common, Sjogren′s syndrome, mixed connective tissue disorders may lead to the rare condition of complete congenital heart block in the neonate. Rare fetal syndromes such as myocarditis, 18p syndrome, mucopolysaccharidoses and mitochondrial diseases are other causes. The mortality rate of this condition is inversely propotional to the age of presentation being 6 % in the neonatal age group. As the cardiac output in the neonate is heart rate dependent, it is crucial to maintain the heart rate in these patients. Pharamacological interventions with dopamine, isoprenaline, epinephrine and atropine are known for their variable response. Although permanent pacing is the most reliable mode of management, the access to it is often not readily available, especially in the developing countries. In such cases temporary pacing methods become lifesaving. Of all the modalities of temporary pacing (transcutaneous, transesophageal and transvenous transcutaneous pacing is the most readily available and immediate mode. In this case report we present a two day old neonate with isolated complete congenital heart block and a resting heart rate of 50-55/min in immediate need of palliative surgery for trachea-esophageal fistula (TEF. With pharmacological intervention the heart rate could only be raised to 75-80/min. The surgery was successfully carried out using transcutaneous pacing to maintain a heart rate of 100/min.

Sedentary lifestyle and state variation in coronary heart disease mortality.

Science.gov (United States)

Yeager, K K; Anda, R F; Macera, C A; Donehoo, R S; Eaker, E D

1995-01-01

Using linear regression, the authors demonstrated a strong association between State-specific coronary heart disease mortality rates and State prevalence of sedentary lifestyle (r2 = 0.34; P = 0.0002) that remained significant after controlling for the prevalence of diagnosed hypertension, smoking, and overweight among the State's population. This ecologic analysis suggests that sedentary lifestyle may explain State variation in coronary heart disease mortality and reinforces the need to include physical activity promotion as a part of programs in the States to prevent heart disease. PMID:7838933

Emerging hemodynamic signatures of the right heart (Third International Right Heart Failure Summit, part 2).

Science.gov (United States)

Maron, Bradley A

2014-12-01

Despite the importance of preserved right ventricular structure and function with respect to outcome across the spectrum of lung, cardiac, and pulmonary vascular diseases, only recently have organized efforts developed to consider the pulmonary vascular-right ventricular apparatus as a specific unit within the larger context of cardiopulmonary pathophysiology. The Third International Right Heart Failure Summit (Boston, MA) was a multidisciplinary event dedicated to promoting a dialogue about the scientific and clinical basis of right heart disease. The current review provides a synopsis of key discussions presented during the section of the summit titled "Emerging Hemodynamic Signatures of the Right Heart." Specifically, topics emphasized in this element of the symposium included (1) the effects of pulmonary vascular dysfunction at rest or provoked by exercise on the right ventricular pressure-volume relationship, (2) the role of pressure-volume loop analysis as a method to characterize right ventricular inefficiency and predict right heart failure, and (3) the importance of a systems biology approach to identifying novel factors that contribute to pathophenotypes associated with pulmonary arterial hypertension and/or right ventricular dysfunction. Collectively, these concepts frame a forward-thinking paradigm shift in the approach to right heart disease by emphasizing factors that regulate the transition from adaptive to maladaptive right ventricular-pulmonary vascular (patho)physiology.

Cardiac magnetic resonance imaging in heart failure: where the alphabet begins!

Science.gov (United States)

Aljizeeri, Ahmed; Sulaiman, Abdulbaset; Alhulaimi, Naji; Alsaileek, Ahmed; Al-Mallah, Mouaz H

2017-07-01

Cardiac Magnetic Resonance Imaging has become a cornerstone in the evaluation of heart failure. It provides a comprehensive evaluation by answering all the pertinent clinical questions across the full pathological spectrum of heart failure. Nowadays, CMR is considered the gold standard in evaluation of ventricular volumes, wall motion and systolic function. Through its unique ability of tissue characterization, it provides incremental diagnostic and prognostic information and thus has emerged as a comprehensive imaging modality in heart failure. This review outlines the role of main conventional CMR sequences in the evaluation of heart failure and their impact in the management and prognosis.

Molecular Epidemiology of Heart Failure

Directory of Open Access Journals (Sweden)

J. Gustav Smith, MD, PhD

2017-12-01

Full Text Available Heart failure (HF is the end-stage of all heart disease and arguably constitutes the greatest unmet therapeutic need in cardiovascular medicine today. Classic epidemiological studies have established clinical risk factors for HF, but the cause remains poorly understood in many cases. Biochemical analyses of small case-control series and animal models have described a plethora of molecular characteristics of HF, but a single unifying pathogenic theory is lacking. Heart failure appears to result not only from cardiac overload or injury but also from a complex interplay among genetic, neurohormonal, metabolic, inflammatory, and other biochemical factors acting on the heart. Recent development of robust, high-throughput tools in molecular biology provides opportunity for deep molecular characterization of population-representative cohorts and HF cases (molecular epidemiology, including genome sequencing, profiling of myocardial gene expression and chromatin modifications, plasma composition of proteins and metabolites, and microbiomes. The integration of such detailed information holds promise for improving understanding of HF pathophysiology in humans, identification of therapeutic targets, and definition of disease subgroups beyond the current classification based on ejection fraction which may benefit from improved individual tailoring of therapy. Challenges include: 1 the need for large cohorts with deep, uniform phenotyping; 2 access to the relevant tissues, ideally with repeated sampling to capture dynamic processes; and 3 analytical issues related to integration and analysis of complex datasets. International research consortia have formed to address these challenges and combine datasets, and cohorts with up to 1 million participants are being collected. This paper describes the molecular epidemiology of HF and provides an overview of methods and tissue types and examples of published and ongoing efforts to systematically evaluate molecular

Decellularized heart ECM hydrogel using supercritical carbon dioxide for improved angiogenesis.

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Seo, Yoojin; Jung, Youngmee; Kim, Soo Hyun

2018-02-01

Initial angiogenesis within the first 3 days is critical for healing ischemic diseases such as myocardial infarction. Recently, decellularized extracellular matrix (dECM) has been reported to provide tissue-derived ECM components and can be used as a scaffold for cell delivery for angiogenesis in tissue engineering. Decellularization by various detergents such as sodium dodecyl sulfate (SDS) and triton X-100 can remove the cell nuclei in tissue organs. However, this leads to ECM structure denaturation, decreased presence of various ECM proteins and cytokines, and loss of mechanical properties. To overcome these limitations, in this study, we developed a supercritical carbon dioxide and ethanol co-solvent (scCO 2 -EtOH) decellularization method, which is a detergent-free system that prevents ECM structure disruption and retains various angiogenic proteins in the heart dECM, and tested on rat heart tissues. The heart tissue was placed into the scCO 2 reactor and decellularized at 37 °C and 350 bar. After scCO 2 -EtOH treatment, the effects were evaluated by DNA, collagen, and glycosaminoglycan (GAG) quantification and hematoxylin and eosin and immunofluorescence staining to determine the absence of nucleic acids and preservation of heart ECM components. Similar to the native group, the scCO 2 -EtOH group contained more ECM components such as collagen, GAGs, collagen I, laminin, and fibronectin and angiogenic factors including vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor and others in comparison to the detergent group. In addition, to estimate angiogenesis of the dECM hydrogels, the neutralized dECM solution was injected in a rat subcutaneous layer (n = 6 in each group: collagen, scCO 2 -EOH, and detergent group), after which the solution naturally formed gelation in the subcutaneous layer. After 3 days, the gels were harvested and estimated by immunofluorescence staining and the ImageJ program for

Functional analysis of human and chimpanzee promoters.

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Heissig, Florian; Krause, Johannes; Bryk, Jaroslaw; Khaitovich, Philipp; Enard, Wolfgang; Pääbo, Svante

2005-01-01

It has long been argued that changes in gene expression may provide an additional and crucial perspective on the evolutionary differences between humans and chimpanzees. To investigate how often expression differences seen in tissues are caused by sequence differences in the proximal promoters, we tested the expression activity in cultured cells of human and chimpanzee promoters from genes that differ in mRNA expression between human and chimpanzee tissues. Twelve promoters for which the corresponding gene had been shown to be differentially expressed between humans and chimpanzees in liver or brain were tested. Seven showed a significant difference in activity between the human promoter and the orthologous chimpanzee promoter in at least one of the two cell lines used. However, only three of them showed a difference in the same direction as in the tissues. Differences in proximal promoter activity are likely to be common between humans and chimpanzees, but are not linked in a simple fashion to gene-expression levels in tissues. This suggests that several genetic differences between humans and chimpanzees might be responsible for a single expression difference and thus that relevant expression differences between humans and chimpanzees will be difficult to predict from cell culture experiments or DNA sequences.

3D imaging of the mitochondrial redox state of rat hearts under normal and fasting conditions

Directory of Open Access Journals (Sweden)

He N. Xu

2014-03-01

Full Text Available The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo. Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD+ couple acting as a central electron carrier. We employed the Chance redox scanner — the low-temperature fluorescence scanner to image the three-dimensional (3D spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH (p = 0.038. No significant change in Fp was found (p = 0.4. The NADH/Fp ratio decreased with a marginal p value (0.076. The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the

3D IMAGING OF THE MITOCHONDRIAL REDOX STATE OF RAT HEARTS UNDER NORMAL AND FASTING CONDITIONS.

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Xu, He N; Zhou, Rong; Moon, Lily; Feng, Min; Li, Lin Z

2014-03-01

The heart requires continuous ATP availability that is generated in the mitochondria. Although studies using the cell culture and perfused organ models have been carried out to investigate the biochemistry in the mitochondria in response to a change in substrate supply, mitochondrial bioenergetics of heart under normal feed or fasting conditions has not been studied at the tissue level with a sub-millimeter spatial resolution either in vivo or ex vivo . Oxidation of many food-derived metabolites to generate ATP in the mitochondria is realized through the NADH/NAD + couple acting as a central electron carrier. We employed the Chance redox scanner - the low-temperature fluorescence scanner to image the three-dimensional (3D) spatial distribution of the mitochondrial redox states in heart tissues of rats under normal feeding or an overnight starvation for 14.5 h. Multiple consecutive sections of each heart were imaged to map three redox indices, i.e., NADH, oxidized flavoproteins (Fp, including flavin adenine dinucleotide (FAD)) and the redox ratio NADH/Fp. The imaging results revealed the micro-heterogeneity and the spatial distribution of these redox indices. The quantitative analysis showed that in the fasted hearts the standard deviation of both NADH and Fp, i.e., SD_NADH and SD_Fp, significantly decreased with a p value of 0.032 and 0.045, respectively, indicating that the hearts become relatively more homogeneous after fasting. The fasted hearts contained 28.6% less NADH ( p = 0.038). No significant change in Fp was found ( p = 0.4). The NADH/Fp ratio decreased with a marginal p value (0.076). The decreased NADH in the fasted hearts is consistent with the cardiac cells' reliance of fatty acids consumption for energy metabolism when glucose becomes scarce. The experimental observation of NADH decrease induced by dietary restriction in the heart at tissue level has not been reported to our best knowledge. The Chance redox scanner demonstrated the feasibility of 3D

In vitro effects of toxaphene on mitochondrial calcium ATPase and calcium uptake in selected rat tissues

International Nuclear Information System (INIS)

Trottman, C.H.; Rao, K.S.P.; Morrow, W.; Uzodinma, J.E.; Desaiah, D.

1985-01-01

In vitro effects of toxaphene on Ca 2+ -ATPase activity and 45 Ca 2+ -uptake were studied in mitochondrial fractions of heart, kidney and liver tissues of rat. Mitochondrial fractions were prepared by the conventional centrifugation method. Ca 2+ -ATPase activity was determined by measuring the inorganic phosphate liberated during ATP hydrolysis. Toxaphene inhibited Ca 2+ -ATPase in a concentration dependent manner in all the three tissues. Substrate activation kinetics, with heart, kidney and liver tissue fractions, revealed that toxaphene inhibited Ca 2+ -ATPase activity non-competetively by decreasing the maximum velocity of the enzyme without affecting the enzyme-substrate affinity. Toxaphene also inhibited mitochondrial 45 Ca 2+ -uptake in the three selected tissues in a concentration dependent manner. These results indicate that toxaphene is an inhibitor of mitochondrial Ca 2+ -ATPase and calcium transport in heart, kidney and liver tissues of rat. 19 references, 5 figures

Kupffer cells activation promoted binge drinking-induced fatty liver by activating lipolysis in white adipose tissues.

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Zhao, Yu-Ying; Yang, Rui; Xiao, Mo; Guan, Min-Jie; Zhao, Ning; Zeng, Tao

2017-09-01

Kupffer cells (KCs) have been suggested to play critical roles in chronic ethanol induced early liver injury, but the role of KCs in binge drinking-induced hepatic steatosis remains unclear. This study was designed to investigate the roles of KCs inhibitor (GdCl 3 ) and TNF-α antagonist (etanercept) on binge drinking-induced liver steatosis and to explore the underlying mechanisms. C57BL/6 mice were exposed to three doses of ethanol (6g/kg body weight) to mimic binge drinking-induced fatty liver. The results showed that both GdCl 3 and etanercept partially but significantly alleviated binge drinking-induced increase of hepatic triglyceride (TG) level, and reduced fat droplets accumulation in mice liver. GdCl 3 but not etanercept significantly blocked binge drinking-induced activation of KCs. However, neither GdCl 3 nor etanercept could affect binge drinking-induced decrease of PPAR-α, ACOX, FAS, ACC and SCD protein levels, or increase of the LC3 II/LC3 I ratio and p62 protein level. Interestingly, both GdCl 3 and etanercept significantly suppressed binge drinking-induced phosphorylation of HSL in epididymal adipose tissues. Results of in vitro studies with cultured epididymal adipose tissues showed that TNF-α could increase the phosphorylation of HSL in adipose tissues and upgrade the secretion of free fatty acid (FFA) in the culture medium. Taken together, KCs inhibitor and TNF-α antagonist could partially attenuate binge drinking-induced liver steatosis, which might be attributed to the suppression of mobilization of white adipose tissues. These results suggest that KCs activation may promote binge drinking-induced fatty liver by TNF-α mediated activation of lipolysis in white adipose tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

Smokeless tobacco, sport and the heart.

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Chagué, Frédéric; Guenancia, Charles; Gudjoncik, Aurélie; Moreau, Daniel; Cottin, Yves; Zeller, Marianne

2015-01-01

Smokeless tobacco (snuff) is a finely ground or shredded tobacco that is sniffed through the nose or placed between the cheek and gum. Chewing tobacco is used by putting a wad of tobacco inside the cheek. Smokeless tobacco is widely used by young athletes to enhance performance because nicotine improves some aspects of physiology. However, smokeless tobacco has harmful health effects, including cardiovascular disorders, linked to nicotine physiological effects, mainly through catecholamine release. Nicotine decreases heart rate variability and the ventricular fibrillation threshold, and promotes the occurrence of various arrhythmias; it also impairs endothelial-dependent vasodilation and could therefore promote premature atherogenesis. At rest, heart rate, blood pressure, inotropism, cardiac output and myocardial oxygen consumption are increased by nicotine, leading to an imbalance between myocardial oxygen demand and supply. The same occurs at submaximal levels of exercise. These increases are accompanied by a rise in systemic resistances. At maximal exercise, heart rate, cardiac output and maximal oxygen uptake (V˙O2max) are unaffected by nicotine. Because endothelial dysfunction is promoted by nicotine, paradoxical coronary vasoconstriction may occur during exercise and recovery. Nicotine induces a decrease in muscular strength and impairs anaerobic performance. However, nicotine is used in sports as it diminishes anxiety, enhances concentration and agility, improves aerobic performance and favours weight control. Importantly, smokeless tobacco, similar to cigarette smoking, leads to nicotine dependence through dopaminergic pathways. Smokeless tobacco has harmful cardiovascular effects and is addictive: it fulfils all the criteria for inclusion in the World Anti-Doping Agency prohibited list as a doping product. Smokeless tobacco use in sporting activities must be discouraged. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Tissue Characterization of Lemna gibba rbcS Promoter%浮萍rbcS启动子组织特性研究

Institute of Scientific and Technical Information of China (English)

黄凤珍; 李倩; 王友如

2015-01-01

A new rbcS (ribulose-1,5-bisphosphate carboxylase small subunit) promoter with the size of 1 438 bp (named SSU5C promoter) was cloned from Lemna gibba. SSU5C promoter was fused with the GUS reporter gene to construct a plant binary vector (pSSU5C-IGUS), and introduced into duckweed by agrogacterium-mediated trans-formation. The transgenic plantlets were generated. This study was focused on the tissue characterization of SSU5C promoter. GUS staining showed that SSU5C promoter drove GUS to express in the green tissue in leaf, stem and petiole of T1 tobacco, whereas no GUS activity was observed in root. In reproductive organs, the GUS activity was observed in corolla lobes, anther and stigma, no GUS activity was observed in other parts. It was obvious that rbcS promoter can not only express in the green tissue, but also can express in reproductive organs. The results lay a good doundation for the application of SSU5C in plant genetic engineering.%SSU5C启动子(全长1438 bp)是从浮萍基因组中新克隆的一个rb c S (ribulose-1,5-bisphosphate carbo-xylase small subunit)启动子。本研究将 SSU5C 启动子与GUS基因融合，成功构建植物双元表达载p SSU5C-IGUS，并利用农杆菌介导法转化烟草，获得转基因植株，探究SSU5C启动子在烟草中的组织表达特点。GUS检测结果表明：在T1烟草的营养器官中，SSU5C启动子主要驱动GUS基因在烟草叶片和叶柄、茎等绿色组织中表达，而在根部不表达；在生殖器官中，GUS基因主要在花冠裂片以及花药和柱头中表达。本研究首次发现浮萍rb c S启动子不仅在绿色组织中表达，而且在生殖器官中的花冠裂片以及花药和柱头中表达，这一发现可为SSU5C启动子在植物基因工程中的应用奠定基础。

Complement activation, endothelial dysfunction, insulin resistance and chronic heart failure

DEFF Research Database (Denmark)

Bjerre, M.; Kistorp, C.; Hansen, T.K.

2010-01-01

Objectives. Patients with chronic heart failure (CHF) have an exaggerated immune response, endothelial damage/dysfunction, and increased risk of diabetes mellitus (DM). The inter-relationship(s) between indices of complement activation (soluble membrane attack complex, sMAC), inflammation (hs...... to ischemic heart disease (IHD) as compared with CHF patients with non-ischemic ethiology (p = 0.02), but were not predictive of survival or progression of CHF. A moderate strong relation between sMAC and sEsel levels was found beta = 0.33 (p ... damaging of the heart tissue...

Heart activity monitoring using 3D hologram based on smartphone.

Science.gov (United States)

Thap, Tharoeun; Heewon Chung; Jinseok Lee

2016-08-01

In this paper, we used smartphone to obtained pulsatile signal from a fingertip by illuminating the skin tissue using flashlight and with an on-board camera to record the change of the light intensity reflected from the tissue. The pulsatile signal is produced by analyzing average green component values of the frames taken by the camera and the heart rate is estimated in real time by detecting the pulse peaks. Based on each instant obtained heartbeat, we design a heart animation that beats according to each interval of the heartbeat. At the same time, we made a simple pyramid shaped hologram from a transparent OHP film to show the heart animation acting above the smartphone screen in three-dimensional view. With this application, users can actually monitor their heart activity in 3D rather than just to see the pulsatile signal graphically. The performances were done in two different conditions: under bright and dark environments. The holograms were made based on three different materials: grey transparent film, clear transparent film, and hard black acrylic board; the grey transparent film provided better performance and we achieved satisfactory results regardless of all environments.

Surface-modified polymers for cardiac tissue engineering.

Science.gov (United States)

Moorthi, Ambigapathi; Tyan, Yu-Chang; Chung, Tze-Wen

2017-09-26

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.

Members of the European Parliament (MEP) Heart Group.

Science.gov (United States)

Tofield, Andros

2013-06-01

The MEP Heart Group is a discussion forum aimed at promoting measures to reduce the burden of cardiovascular disease in the European Union and raise cardiovascular disease as a priority on the EU political agenda.

Exploring lifestyle changes in women with ischemic heart disease

DEFF Research Database (Denmark)

Wagner, Malene; Nielsen, Karina; Jensen, Peter Errboe

2017-01-01

Ischemic heart disease (IHD) is a major cause of death for women worldwide, and thus it is important to focus on lifestyle changes to reduce the impact of the disease on women’s everyday lives. Nine women were interviewed using an explorative approach to describe women’s lifestyle changes after...... being diagnosed with IHD. Three major themes emerged; ‘Heart disease: A life-changing event’, ‘Social life – both inhibiting and promoting lifestyle changes’ and ‘Maintaining changes: An ongoing challenge and a conscious choice’. Ischemic heart disease caused anxiety, and the women strived to find...

miRNAs as therapeutic targets in ischemic heart disease.

Science.gov (United States)

Frost, Robert J A; van Rooij, Eva

2010-06-01

Ischemic heart disease is a form of congestive heart failure that is caused by insufficient blood supply to the heart, resulting in a loss of viable tissue. In response to the injury, the non-ischemic myocardium displays signs of secondary remodeling, like interstitial fibrosis and hypertrophy of cardiac myocytes. This remodeling process further deteriorates pump function and increases susceptibility to arrhythmias. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression in a sequence-dependent manner. Recently, several groups identified miRNAs as crucial gene regulators in response to myocardial infarction (MI) and during post-MI remodeling. In this review, we discuss how modulation of these miRNAs represents a promising new therapeutic strategy to improve the clinical outcome in ischemic heart disease.

Co-purification of arrestin like proteins with alpha-enolase from bovine myocardial tissues and the possible role in heart diseases as an autoantigen

Energy Technology Data Exchange (ETDEWEB)

Mirshahi, M., E-mail: massoud.mirshahi@inserm.fr; Le Marchand, S.

2015-05-08

Aim: Previously, we reported that visual arrestin co-purified with glycolytic enzymes. The aim of this study was to analyze the co-purification of arrestin like proteins (ALP) in bovine cardiac tissues with enolases. Methods: The soluble extract of bovine myocardial tissues from different regions such as left and right atriums and ventricles of the bovine heart (n = 3) was analyzed by ACA-34 gel filtration, immuno-affinity column, SDS-PAGE, ELISA, western blot and a sandwich immune assay for quantification of ALP and sequence analysis. Results: We observed that; 1) The cardiac muscle contained a 50 kDa ALP at a concentration of 751 pg/mg of soluble protein extract, 2) ALP purified, by immunoaffinity, contained alpha-enolase of 48 kDa confirmed by protein sequence analysis; 3) Cardiomyocyte cells exposed to anti arrestin and anti enolase monoclonal antibodies showed decreased proliferation in vitro, 4) High level of autoantibodies were detected by ELISA (3.57% for arrestin and 9.12% for α-enolase) in serum of patients with infarcted heart disease. Conclusion: We suggest a possible interaction between ALP and alpha-enolases yielding a complex that may be involved in the induction of cardiac autoimmune diseases. - Highlights: • We examine a possible interaction between arrestin like protein and alpha-enolases in cardiomyocyte. • We demonstrated the effect of antibodies against arrestin and enolase on cardiomyocyte cell proliferation. • We suggest that this proteins complex may be involved in the induction of cardiac autoimmune diseases.

Activity and immunohistochemical localization of porphobilinogen deaminase in rat tissues

DEFF Research Database (Denmark)

Jørgensen, P E; Erlandsen, E J; Poulsen, Steen Seier

2000-01-01

the activity and the immunohistochemical localization of PBGD in the following tissues of wistar female rats: brain, heart, submandibular gland, liver, kidney, pancreas, ovary, stomach, duodenum, jejunum, ileum, colon and musculature. The PBGD activity varied considerably among the tissues. It was highest...

Fractionated magnetic-resonance elastography on the human heart

International Nuclear Information System (INIS)

Rump, Jens

2008-01-01

Imaging techniques, including magnetic resonance imaging, belong to the most important tools in modern medical diagnostics. Another diagnostic aid is palpation, which is suitable for the qualitative characterization of pathological changes in organs near the surface. Magnetic resonance elastography (MRE) is a combination of these techniques. In principle, MRE uses motionsensitive MR-imaging to depict tissue deformation caused by externally induced shear waves. The type of deformation supply useful information about the elasticity of the tissue. Cardiac disorders are among the most common diseases. The goal of this study was to develop a method of applying in-vivo MRE to the human heart. The development of the mechanical stimulus, ultimately resulting in the introduction of an audio speaker as the source of vibration, provided the necessary means to introduce vibrations into inner organs. A crucial factor in applying MRE to the heart is the speed of the recording, which led to the development of ''fractional MRE''. The currently conventional fast heart imaging techniques were used as a starting point. The use of an unbalanced phase preparation gradient in the balanced steady-state imaging technique resulted in an improved phase-to-noise ratio. Along with the spoiled steady-state MRE imaging technique, initial MRE-studies on the human heart were performed. For the first time, externally induced mechanical vibrations were successfully introduced into the heart and were detected using fractional MRE with a high temporal resolution. The modulation of the shear wave amplitudes observed in the myocard of 6 healthy subjects correlated with the phases of the cardiac cycle. The techniques and methods developed here are a step toward routine clinical application of MRE of the heart and indicate high potential in the area of early diagnosis of cardiac disease. (orig.)

Growth hormone-releasing hormone promotes survival of cardiac myocytes in vitro and protects against ischaemia-reperfusion injury in rat heart.

Science.gov (United States)

Granata, Riccarda; Trovato, Letizia; Gallo, Maria Pia; Destefanis, Silvia; Settanni, Fabio; Scarlatti, Francesca; Brero, Alessia; Ramella, Roberta; Volante, Marco; Isgaard, Jorgen; Levi, Renzo; Papotti, Mauro; Alloatti, Giuseppe; Ghigo, Ezio

2009-07-15

The hypothalamic neuropeptide growth hormone-releasing hormone (GHRH) stimulates GH synthesis and release in the pituitary. GHRH also exerts proliferative effects in extrapituitary cells, whereas GHRH antagonists have been shown to suppress cancer cell proliferation. We investigated GHRH effects on cardiac myocyte cell survival and the underlying signalling mechanisms. Reverse transcriptase-polymerase chain reaction analysis showed GHRH receptor (GHRH-R) mRNA in adult rat ventricular myocytes (ARVMs) and in rat heart H9c2 cells. In ARVMs, GHRH prevented cell death and caspase-3 activation induced by serum starvation and by the beta-adrenergic receptor agonist isoproterenol. The GHRH-R antagonist JV-1-36 abolished GHRH survival action under both experimental conditions. GHRH-induced cardiac cell protection required extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide-3 kinase (PI3K)/Akt activation and adenylyl cyclase/cAMP/protein kinase A signalling. Isoproterenol strongly upregulated the mRNA and protein of the pro-apoptotic inducible cAMP early repressor, whereas GHRH completely blocked this effect. Similar to ARVMs, in H9c2 cardiac cells, GHRH inhibited serum starvation- and isoproterenol-induced cell death and apoptosis through the same signalling pathways. Finally, GHRH improved left ventricular recovery during reperfusion and reduced infarct size in Langendorff-perfused rat hearts, subjected to ischaemia-reperfusion (I/R) injury. These effects involved PI3K/Akt signalling and were inhibited by JV-1-36. Our findings suggest that GHRH promotes cardiac myocyte survival through multiple signalling mechanisms and protects against I/R injury in isolated rat heart, indicating a novel cardioprotective role of this hormone.

Nonmuscle Tissues Contribution to Cancer Cachexia

Directory of Open Access Journals (Sweden)

Josep M. Argilés

2015-01-01

Full Text Available Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white, brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting. This suggests that cachexia is indeed a multiorgan syndrome. Bearing all this in mind, the aim of the present review is to examine the impact of nonmuscle tissues in cancer cachexia.

Bone Morphogenetic Protein 9 Reduces Cardiac Fibrosis and Improves Cardiac Function in Heart Failure.

Science.gov (United States)

Morine, Kevin J; Qiao, Xiaoying; York, Sam; Natov, Peter S; Paruchuri, Vikram; Zhang, Yali; Aronovitz, Mark J; Karas, Richard H; Kapur, Navin K

2018-02-27

Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity. Methods -We examined BMP9 expression and signaling in human cardiac fibroblasts and human subjects with heart failure. We utilized the thoracic aortic constriction (TAC) induced model of heart failure to evaluate the functional effect of BMP9 signaling on cardiac remodeling. Results -BMP9 expression is increased in the circulation and left ventricle (LV) of human subjects with heart failure and is expressed by cardiac fibroblasts. Next, we observed that BMP9 attenuates Type I collagen synthesis in human cardiac fibroblasts using recombinant human BMP9 and an siRNA approach. In BMP9 -/- mice subjected to TAC, loss of BMP9 activity promotes cardiac fibrosis, impairs LV function, and increases LV levels of phosphorylated Smad3 (pSmad3), not pSmad1. In contrast, treatment of wild-type mice subjected to TAC with recombinant BMP9 limits progression of cardiac fibrosis, improves LV function, enhances myocardial capillary density, and increases LV levels of pSmad1, not pSmad3 compared to vehicle treated controls. Since endoglin binds BMP9 with high affinity, we explored the effect of reduced endoglin activity on BMP9 activity. Neutralizing endoglin activity in human cardiac fibroblasts or in wild-type mice subjected to TAC induced heart failure limits collagen production, increases BMP9 protein levels, and increases

Heart failure and atrial fibrillation: current concepts and controversies.

Science.gov (United States)

Van den Berg, M. P.; Tuinenburg, A. E.; Crijns, H. J.; Van Gelder, I. C.; Gosselink, A. T.; Lie, K. I.

1997-01-01

Heart failure and atrial fibrillation are very common, particularly in the elderly. Owing to common risk factors both disorders are often present in the same patient. In addition, there is increasing evidence of a complex, reciprocal relation between heart failure and atrial fibrillation. Thus heart failure may cause atrial fibrillation, with electromechanical feedback and neurohumoral activation playing an important mediating role. In addition, atrial fibrillation may promote heart failure; in particular, when there is an uncontrolled ventricular rate, tachycardiomyopathy may develop and thereby heart failure. Eventually, a vicious circle between heart failure and atrial fibrillation may form, in which neurohumoral activation and subtle derangement of rate control are involved. Treatment should aim at unloading of the heart, adequate control of ventricular rate, and correction of neurohumoral activation. Angiotensin converting enzyme inhibitors may help to achieve these goals. Treatment should also include an attempt to restore sinus rhythm through electrical cardioversion, though appropriate timing of cardioversion is difficult. His bundle ablation may be used to achieve adequate rate control in drug refractory cases. PMID:9155607

Advantages and Limitations of Direct PCR Amplification of Bacterial 16S-rDNA from Resected Heart Tissue or Swabs Followed by Direct Sequencing for Diagnosing Infective Endocarditis: A Retrospective Analysis in the Routine Clinical Setting.

Science.gov (United States)

Maneg, Daniela; Sponsel, Janina; Müller, Iris; Lohr, Benedikt; Penders, John; Madlener, Katharina; Hunfeld, Klaus-Peter

2016-01-01

Infective endocarditis (IE) is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5%) with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke's diagnostic classification scheme.

Tissue-specific regulation of mouse MicroRNA genes in endoderm-derived tissues

OpenAIRE

Gao, Yan; Schug, Jonathan; McKenna, Lindsay B.; Le Lay, John; Kaestner, Klaus H.; Greenbaum, Linda E.

2010-01-01

MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here, we determine the entire microRNAome of three endoderm-derived tissues, liver, jejunum and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After...

Combinatorial polymer electrospun matrices promote physiologically-relevant cardiomyogenic stem cell differentiation.

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Mukesh K Gupta

Full Text Available Myocardial infarction results in extensive cardiomyocyte death which can lead to fatal arrhythmias or congestive heart failure. Delivery of stem cells to repopulate damaged cardiac tissue may be an attractive and innovative solution for repairing the damaged heart. Instructive polymer scaffolds with a wide range of properties have been used extensively to direct the differentiation of stem cells. In this study, we have optimized the chemical and mechanical properties of an electrospun polymer mesh for directed differentiation of embryonic stem cells (ESCs towards a cardiomyogenic lineage. A combinatorial polymer library was prepared by copolymerizing three distinct subunits at varying molar ratios to tune the physicochemical properties of the resulting polymer: hydrophilic polyethylene glycol (PEG, hydrophobic poly(ε-caprolactone (PCL, and negatively-charged, carboxylated PCL (CPCL. Murine ESCs were cultured on electrospun polymeric scaffolds and their differentiation to cardiomyocytes was assessed through measurements of viability, intracellular reactive oxygen species (ROS, α-myosin heavy chain expression (α-MHC, and intracellular Ca(2+ signaling dynamics. Interestingly, ESCs on the most compliant substrate, 4%PEG-86%PCL-10%CPCL, exhibited the highest α-MHC expression as well as the most mature Ca(2+ signaling dynamics. To investigate the role of scaffold modulus in ESC differentiation, the scaffold fiber density was reduced by altering the electrospinning parameters. The reduced modulus was found to enhance α-MHC gene expression, and promote maturation of myocyte Ca(2+ handling. These data indicate that ESC-derived cardiomyocyte differentiation and maturation can be promoted by tuning the mechanical and chemical properties of polymer scaffold via copolymerization and electrospinning techniques.

Engineering vascular development for tissue regeneration

NARCIS (Netherlands)

Rivron, N.C.

2010-01-01

Tissue engineering and regenerative medicine aim at restoring a damaged tissue by recreating in vitro or promoting its regeneratin in vovo. The vasculature is central to these therapies for the irrigation of the defective tissue (oxygen, nutrients or circulating regenerative cells) and as an

Soft tissue engineering with micronized-gingival connective tissues.

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Noda, Sawako; Sumita, Yoshinori; Ohba, Seigo; Yamamoto, Hideyuki; Asahina, Izumi

2018-01-01

The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm 3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. © 2017 Wiley Periodicals, Inc.

“The Heart Truth:” Using the Power of Branding and Social Marketing to Increase Awareness of Heart Disease in Women

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Long, Terry; Taubenheim, Ann; Wayman, Jennifer; Temple, Sarah; Ruoff, Beth

2008-01-01

In September 2002, the National Heart, Lung, and Blood Institute launched The Heart Truth, the first federally-sponsored national campaign aimed at increasing awareness among women about their risk of heart disease. A traditional social marketing approach, including an extensive formative research phase, was used to plan, implement, and evaluate the campaign. With the creation of the Red Dress as the national symbol for women and heart disease awareness, the campaign integrated a branding strategy into its social marketing framework. The aim was to develop and promote a women's heart disease brand that would create a strong emotional connection with women. The Red Dress brand has had a powerful appeal to a wide diversity of women and has given momentum to the campaign's three-part implementation strategy of partnership development, media relations, and community action. In addition to generating its own substantial programming, The Heart Truth became a catalyst for a host of other national and local educational initiatives, both large and small. By the campaign's fifth anniversary, surveys showed that women were increasingly aware of heart disease as their leading cause of death and that the rise in awareness was associated with increased action to reduce heart disease risk. PMID:19122892

An Intergenic Region Shared by At4g35985 and At4g35987 in Arabidopsis thaliana Is a Tissue Specific and Stress Inducible Bidirectional Promoter Analyzed in Transgenic Arabidopsis and Tobacco Plants

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Banerjee, Joydeep; Sahoo, Dipak Kumar; Dey, Nrisingha; Houtz, Robert L.; Maiti, Indu Bhushan

2013-01-01

On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85) showed stronger expression (about 3.5 fold) compared to the At4g35987 promoter (P87). The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold) under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications. PMID:24260266

An intergenic region shared by At4g35985 and At4g35987 in Arabidopsis thaliana is a tissue specific and stress inducible bidirectional promoter analyzed in transgenic arabidopsis and tobacco plants.

Directory of Open Access Journals (Sweden)

Joydeep Banerjee

Full Text Available On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985 are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85 showed stronger expression (about 3.5 fold compared to the At4g35987 promoter (P87. The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications.

Rapid upregulation of heart antioxidant enzymes during arousal from estivation in the Giant African snail (Achatina fulica).

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Salway, Kurtis D; Tattersall, Glenn J; Stuart, Jeffrey A

2010-11-01

Estivation is an adaptive response to environments characterized by elevated temperatures and desiccative stress, as may occur during summer dry seasons. Similar to diapause and hibernation, it is characterized by low levels of activity, a drastically suppressed metabolic rate and enhanced stress resistance. We tested the hypothesis that Achatina fulica, a pulmonate land snail, enhances stress resistance during estivation and/or arousal by upregulating intracellular antioxidant defenses in the heart, kidney, hepatopancreas and foot tissues. No statistically significant changes in mitochondrial or cytosolic superoxide dismutase levels or activities, or glutathione peroxidase, glutathione reductase or catalase activities were associated with estivation in any tissue, however. In contrast, during arousal from estivation, activities of several antioxidant enzymes increased in heart, hepatopancreas and foot. In heart, a rapid increase in MnSOD protein levels was observed that peaked at 2h post arousal, but no such change was observed in CuZnSOD protein levels. Glutathione peroxidase activity was upregulated at 1h post arousal and remained elevated until 8h post arousal in heart tissue. Glutathione peroxidase was also upregulated at 24h post arousal in foot tissue. Glutathione reductase activity was upregulated at 4h post arousal in heart and foot tissues whereas catalase activity showed no changes. Markers of lipid peroxidation and protein damage revealed no significant increases during estivation or arousal. Therefore, antioxidant enzymes may play a role in oxidative stress defense specifically during arousal from estivation in A. fulica. Copyright 2010 Elsevier Inc. All rights reserved.

Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

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Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

2010-11-01

The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate

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Burkhard, Silja Barbara

2018-01-01

Development of specialized cells and structures in the heart is regulated by spatially -restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development we used tomo-seq, combining high-throughput RNA-sequencing with tissue-sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development. Using our transcriptome map, we identified spatially restricted Wnt/β-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/β-catenin signaling controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially restricted molecular pathways critical for specific cardiac functions. PMID:29400650

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

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Shah, Nisarg J.; Hyder, Md. Nasim; Quadir, Mohiuddin A.; Dorval Courchesne, Noémie-Manuelle; Seeherman, Howard J.; Nevins, Myron; Spector, Myron; Hammond, Paula T.

2014-01-01

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration. PMID:25136093

Obesity and heart failure as a mediator of the cerebrorenal interaction.

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Jindal, Ankur; Whaley-Connell, Adam; Sowers, James R

2013-01-01

The obesity epidemic is contributing substantially to the burden of cardiovascular disease including heart disease and congestive heart failure, in the United States and the rest of the world. Overnutrition as a driver of obesity, promotes alterations in fatty acid, lipid, and glucose metabolism that influence myocardial function and progression of heart failure from diastolic to systolic failure. The association of progressive heart failure and progressive chronic kidney disease is well documented and often referred to as the cardiorenal syndrome, as well as a prognosticator for cerebrovascular disease (e.g. stroke). Whether the relationship between obesity, heart disease/failure and risk for chronic kidney disease and stroke is direct or a confluence of risk factors is poorly understood. Copyright © 2013 S. Karger AG, Basel.

Transgenic zebrafish reveal tissue-specific differences in estrogen signaling in response to environmental water samples.

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Gorelick, Daniel A; Iwanowicz, Luke R; Hung, Alice L; Blazer, Vicki S; Halpern, Marnie E

2014-04-01

Environmental endocrine disruptors (EEDs) are exogenous chemicals that mimic endogenous hormones such as estrogens. Previous studies using a zebrafish transgenic reporter demonstrated that the EEDs bisphenol A and genistein preferentially activate estrogen receptors (ERs) in the larval heart compared with the liver. However, it was not known whether the transgenic zebrafish reporter was sensitive enough to detect estrogens from environmental samples, whether environmental estrogens would exhibit tissue-specific effects similar to those of BPA and genistein, or why some compounds preferentially target receptors in the heart. We tested surface water samples using a transgenic zebrafish reporter with tandem estrogen response elements driving green fluorescent protein expression (5xERE:GFP). Reporter activation was colocalized with tissue-specific expression of ER genes by RNA in situ hybridization. We observed selective patterns of ER activation in transgenic fish exposed to river water samples from the Mid-Atlantic United States, with several samples preferentially activating receptors in embryonic and larval heart valves. We discovered that tissue specificity in ER activation was due to differences in the expression of ER subtypes. ERα was expressed in developing heart valves but not in the liver, whereas ERβ2 had the opposite profile. Accordingly, subtype-specific ER agonists activated the reporter in either the heart valves or the liver. The use of 5xERE:GFP transgenic zebrafish revealed an unexpected tissue-specific difference in the response to environmentally relevant estrogenic compounds. Exposure to estrogenic EEDs in utero was associated with adverse health effects, with the potentially unanticipated consequence of targeting developing heart valves.

Tuning flux: autophagy as a target of heart disease therapy

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Xie, Min; Morales, Cyndi R.; Lavandero, Sergio; Hill, Joseph A.

2013-01-01

Purpose of review Despite maximum medical and mechanical support therapy, heart failure remains a relentlessly progressive disorder with substantial morbidity and mortality. Autophagy, an evolutionarily conserved process of cellular cannibalization, has been implicated in virtually all forms of cardiovascular disease. Indeed, its role is context dependent, antagonizing or promoting disease depending on the circumstance. Here, we review current understanding of the role of autophagy in the pathogenesis of heart failure and explore this pathway as a target of therapeutic intervention. Recent findings In preclinical models of heart disease, cardiomyocyte autophagic flux is activated; indeed, its role in disease pathogenesis is the subject of intense investigation to define mechanism. Similarly, in failing human heart of a variety of etiologies, cardiomyocyte autophagic activity is upregulated, and therapy, such as with mechanical support systems, elicits declines in autophagy activity. However, when suppression of autophagy is complete, rapid and catastrophic cell death occurs, consistent with a model in which basal autophagic flux is required for proteostasis. Thus, a narrow zone of ‘optimal’ autophagy seems to exist. The challenge moving forward is to tune the stress-triggered autophagic response within that ‘sweet spot’ range for therapeutic benefit. Summary Whereas we have known for some years of the participation of lysosomal mechanisms in heart disease, it is only recently that upstream mechanisms (autophagy) are being explored. The challenge for the future is to dissect the underlying circuitry and titrate the response into an optimal, proteostasis-promoting range in hopes of mitigating the ever-expanding epidemic of heart failure. PMID:21415729

Connective tissue fibroblasts and Tcf4 regulate myogenesis

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Mathew, Sam J.; Hansen, Jody M.; Merrell, Allyson J.; Murphy, Malea M.; Lawson, Jennifer A.; Hutcheson, David A.; Hansen, Mark S.; Angus-Hill, Melinda; Kardon, Gabrielle

2011-01-01

Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis. PMID:21177349

Tissue and Organ 3D Bioprinting.

Science.gov (United States)

Xia, Zengmin; Jin, Sha; Ye, Kaiming

2018-02-01

Three-dimensional (3D) bioprinting enables the creation of tissue constructs with heterogeneous compositions and complex architectures. It was initially used for preparing scaffolds for bone tissue engineering. It has recently been adopted to create living tissues, such as cartilage, skin, and heart valve. To facilitate vascularization, hollow channels have been created in the hydrogels by 3D bioprinting. This review discusses the state of the art of the technology, along with a broad range of biomaterials used for 3D bioprinting. It provides an update on recent developments in bioprinting and its applications. 3D bioprinting has profound impacts on biomedical research and industry. It offers a new way to industrialize tissue biofabrication. It has great potential for regenerating tissues and organs to overcome the shortage of organ transplantation.

Interleukin-1β regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

International Nuclear Information System (INIS)

Zitta, Karina; Brandt, Berenice; Wuensch, Annegret; Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens; Albrecht, Martin

2010-01-01

Research highlights: → Levels of IL-1β are increased in the pig myocardium after infarction. → Cultured pig heart cells possess IL-1 receptors. → IL-1β increases cell proliferation of pig heart cells in-vitro. → IL-1β increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. → IL-1β may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1β is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1β on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1β. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1β resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1β (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1β plays a major role in the events of tissue remodelling in the heart. Combined with our recently published in vivo data (Meybohm et al., PLoS One

Interleukin-1{beta} regulates cell proliferation and activity of extracellular matrix remodelling enzymes in cultured primary pig heart cells

Energy Technology Data Exchange (ETDEWEB)

Zitta, Karina; Brandt, Berenice [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Wuensch, Annegret [Institute of Molecular Animal Breeding and Biotechnology, Ludwig Maximilians University, Munich (Germany); Meybohm, Patrick; Bein, Berthold; Steinfath, Markus; Scholz, Jens [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany); Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de [Department of Anesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel (Germany)

2010-09-03

Research highlights: {yields} Levels of IL-1{beta} are increased in the pig myocardium after infarction. {yields} Cultured pig heart cells possess IL-1 receptors. {yields} IL-1{beta} increases cell proliferation of pig heart cells in-vitro. {yields} IL-1{beta} increases MMP-2 and MMP-9 activity in pig heart cells in-vitro. {yields} IL-1{beta} may be important for tissue remodelling events after myocardial infarction. -- Abstract: After myocardial infarction, elevated levels of interleukins (ILs) are found within the myocardial tissue and IL-1{beta} is considered to play a major role in tissue remodelling events throughout the body. In the study presented, we have established a cell culture model of primary pig heart cells to evaluate the effects of different concentrations of IL-1{beta} on cell proliferation as well as expression and activity of enzymes typically involved in tissue remodelling. Primary pig heart cell cultures were derived from three different animals and stimulated with recombinant pig IL-1{beta}. RNA expression was detected by RT-PCR, protein levels were evaluated by Western blotting, activity of matrix metalloproteinases (MMPs) was quantified by gelatine zymography and cell proliferation was measured using colorimetric MTS assays. Pig heart cells express receptors for IL-1 and application of IL-1{beta} resulted in a dose-dependent increase of cell proliferation (P < 0.05 vs. control; 100 ng/ml; 24 h). Gene expression of caspase-3 was increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h), and pro-caspase-3 but not active caspase was detected in lysates of pig heart cells by Western blotting. MMP-2 gene expression as well as enzymatic activities of MMP-2 and MMP-9 were increased by IL-1{beta} (P < 0.05 vs. control; 100 ng/ml; 3 h for gene expression, 48 and 72 h for enzymatic activities of MMP-2 and MMP-9, respectively). Our in vitro data suggest that IL-1{beta} plays a major role in the events of tissue remodelling in the heart. Combined

Cigarette smoke promotes dendritic cell accumulation in COPD; a Lung Tissue Research Consortium study

Directory of Open Access Journals (Sweden)

Yi Eunhee S

2010-04-01

Full Text Available Abstract Background Abnormal immune responses are believed to be highly relevant in the pathogenesis of chronic obstructive pulmonary disease (COPD. Dendritic cells provide a critical checkpoint for immunity by their capacity to both induce and suppress immunity. Although evident that cigarette smoke, the primary cause of COPD, significantly influences dendritic cell functions, little is known about the roles of dendritic cells in the pathogenesis of COPD. Methods The extent of dendritic cell infiltration in COPD tissue specimens was determined using immunohistochemical localization of CD83+ cells (marker of matured myeloid dendritic cells, and CD1a+ cells (Langerhans cells. The extent of tissue infiltration with Langerhans cells was also determined by the relative expression of the CD207 gene in COPD versus control tissues. To determine mechanisms by which dendritic cells accumulate in COPD, complimentary studies were conducted using monocyte-derived human dendritic cells exposed to cigarette smoke extract (CSE, and dendritic cells extracted from mice chronically exposed to cigarette smoke. Results In human COPD lung tissue, we detected a significant increase in the total number of CD83+ cells, and significantly higher amounts of CD207 mRNA when compared with control tissue. Human monocyte-derived dendritic cells exposed to CSE (0.1-2% exhibited enhanced survival in vitro when compared with control dendritic cells. Murine dendritic cells extracted from mice exposed to cigarette smoke for 4 weeks, also demonstrated enhanced survival compared to dendritic cells extracted from control mice. Acute exposure of human dendritic cells to CSE induced the cellular pro-survival proteins heme-oxygenase-1 (HO-1, and B cell lymphoma leukemia-x(L (Bcl-xL, predominantly through oxidative stress. Although activated human dendritic cells conditioned with CSE expressed diminished migratory CCR7 expression, their migration towards the CCR7 ligand CCL21 was not

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association.

Science.gov (United States)

Doehner, Wolfram; Ural, Dilek; Haeusler, Karl Georg; Čelutkienė, Jelena; Bestetti, Reinaldo; Cavusoglu, Yuksel; Peña-Duque, Marco A; Glavas, Duska; Iacoviello, Massimo; Laufs, Ulrich; Alvear, Ricardo Marmol; Mbakwem, Amam; Piepoli, Massimo F; Rosen, Stuart D; Tsivgoulis, Georgios; Vitale, Cristiana; Yilmaz, M Birhan; Anker, Stefan D; Filippatos, Gerasimos; Seferovic, Petar; Coats, Andrew J S; Ruschitzka, Frank

2018-02-01

Heart failure (HF) is a complex clinical syndrome with multiple interactions between the failing myocardium and cerebral (dys-)functions. Bi-directional feedback interactions between the heart and the brain are inherent in the pathophysiology of HF: (i) the impaired cardiac function affects cerebral structure and functional capacity, and (ii) neuronal signals impact on the cardiovascular continuum. These interactions contribute to the symptomatic presentation of HF patients and affect many co-morbidities of HF. Moreover, neuro-cardiac feedback signals significantly promote aggravation and further progression of HF and are causal in the poor prognosis of HF. The diversity and complexity of heart and brain interactions make it difficult to develop a comprehensive overview. In this paper a systematic approach is proposed to develop a comprehensive atlas of related conditions, signals and disease mechanisms of the interactions between the heart and the brain in HF. The proposed taxonomy is based on pathophysiological principles. Impaired perfusion of the brain may represent one major category, with acute (cardio-embolic) or chronic (haemodynamic failure) low perfusion being sub-categories with mostly different consequences (i.e. ischaemic stroke or cognitive impairment, respectively). Further categories include impairment of higher cortical function (mood, cognition), of brain stem function (sympathetic over-activation, neuro-cardiac reflexes). Treatment-related interactions could be categorized as medical, interventional and device-related interactions. Also interactions due to specific diseases are categorized. A methodical approach to categorize the interdependency of heart and brain may help to integrate individual research areas into an overall picture. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

Post-radiotherapeutic heart lesions

International Nuclear Information System (INIS)

Testart, F.M.

1979-05-01

Heart structures have traditionally been considered radioresistant. In fact all tissues subjected to radiotherapy can develop lesions. Possible damage includes: - pericardiac fibrosis, the commonest and best individualized, associated with a constriction this leads to a stoppage pattern usually occurring late, around the 18th month. Its frequency depends directly on the total radiation dose; - fibrous myocarditis by direct damage to the heart muscle; - stenosis type lesions of the large coronary trunks; - in exceptional cases lesions of the aorta: hyperplastic degenerescence of the intima and adventitia or of the aortic sigmoid valvules and the mitral valves. Three observations are reported, concerning a coronary, a pericardiac and a coronary, myocardiac and pericardiac lesion. Following this account the irradiation techniques and main experimental data are reviewed and the prophylactic and therapeutic consequences to be derived from our observations and those of the literature are examined [fr

A PKM2 signature in the failing heart

Science.gov (United States)

Rees, Meredith L.; Subramaniam, Janani; Li, Yuanteng; Hamilton, Dale J.; Frazier, O. Howard; Taegtmeyer, Heinrich

2015-01-01

A salient feature of the failing heart is metabolic remodeling towards predominant glucose metabolism and activation of the fetal gene program. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor used for the treatment of highly vascularized tumors. In diabetic patients, sunitinib significantly decreases blood glucose. However, a considerable proportion of sunitinib-treated patients develop cardiac dysfunction or failure. We asked whether sunitinib treatment results in shift towards glycolysis in the heart. Glucose uptake by the heart was increased fivefold in mice treated with sunitinib. Transcript analysis by qPCR revealed an induction of genes associated with glycolysis and reactivation of the fetal gene program. Additionally, we observed a shift in the enzyme pyruvate kinase from the adult M1 (PKM1) isoform to the fetal M2 (PKM2) isoform, a hallmark of the Warburg Effect. This novel observation led us to examine whether a similar shift occurs in human heart failure. Examination of tissue from patients with heart failure similarly displayed an induction of PKM2. Moreover, this phenomenon was partially reversed following mechanical unloading. We propose that pyruvate kinase isoform switching represents a novel feature of the fetal gene program in the failing heart. PMID:25735978

Low dose trichloroethylene alters cytochrome P450 - 2C subfamily expression in the developing chick heart

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Makwana, Om; Ahles, Lauren; Lencinas, Alejandro; Selmin, Ornella I.; Runyan, Raymond B.

2013-01-01

Trichloroethylene (TCE) is an organic solvent and common environmental contaminant. TCE exposure is associated with heart defects in humans and animal models. Primary metabolism of TCE in adult rodent models is by specific hepatic cytochrome P450 enzymes (Lash et al., 2000). As association of TCE exposure with cardiac defects is in exposed embryos prior to normal liver development, we investigated metabolism of TCE in the early embryo. Developing chick embryos were dosed in ovo with environmentally relevant doses of TCE (8 ppb and 800 ppb) and RNA was extracted from cardiac and extra-cardiac tissue (whole embryo without heart). Real time PCR showed upregulation of CYP2H1 transcripts in response to TCE exposure in the heart. No detectable cytochrome expression was found in extra-cardiac tissue. As seen previously, the dose response was non-monotonic and 8ppb elicited stronger upregulation than 800 ppb. Immunostaining for CYP2C subfamily expression confirmed protein expression and showed localization in both myocardium and endothelium. TCE exposure increased protein expression in both tissues. These data demonstrate that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart. Expression of these CYPs is likely to be relevant to the susceptibility of the developing heart to environmental teratogens. PMID:22855351

Nonlinear and Stochastic Dynamics in the Heart

Science.gov (United States)

Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.

2014-01-01

In a normal human life span, the heart beats about 2 to 3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems. PMID:25267872

Nonlinear and stochastic dynamics in the heart

Energy Technology Data Exchange (ETDEWEB)

Qu, Zhilin, E-mail: zqu@mednet.ucla.edu [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Hu, Gang [Department of Physics, Beijing Normal University, Beijing 100875 (China); Garfinkel, Alan [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095 (United States); Weiss, James N. [Department of Medicine (Cardiology), David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States); Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095 (United States)

2014-10-10

In a normal human life span, the heart beats about 2–3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems.

Nonlinear and stochastic dynamics in the heart

International Nuclear Information System (INIS)

Qu, Zhilin; Hu, Gang; Garfinkel, Alan; Weiss, James N.

2014-01-01

In a normal human life span, the heart beats about 2–3 billion times. Under diseased conditions, a heart may lose its normal rhythm and degenerate suddenly into much faster and irregular rhythms, called arrhythmias, which may lead to sudden death. The transition from a normal rhythm to an arrhythmia is a transition from regular electrical wave conduction to irregular or turbulent wave conduction in the heart, and thus this medical problem is also a problem of physics and mathematics. In the last century, clinical, experimental, and theoretical studies have shown that dynamical theories play fundamental roles in understanding the mechanisms of the genesis of the normal heart rhythm as well as lethal arrhythmias. In this article, we summarize in detail the nonlinear and stochastic dynamics occurring in the heart and their links to normal cardiac functions and arrhythmias, providing a holistic view through integrating dynamics from the molecular (microscopic) scale, to the organelle (mesoscopic) scale, to the cellular, tissue, and organ (macroscopic) scales. We discuss what existing problems and challenges are waiting to be solved and how multi-scale mathematical modeling and nonlinear dynamics may be helpful for solving these problems

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

Science.gov (United States)

Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

2018-01-16

Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans.

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Rutkovskiy, Arkady; Sagave, Julia; Czibik, Gabor; Baysa, Anton; Zihlavnikova Enayati, Katarina; Hillestad, Vigdis; Dahl, Christen Peder; Fiane, Arnt; Gullestad, Lars; Gravning, Jørgen; Ahmed, Shakil; Attramadal, Håvard; Valen, Guro; Vaage, Jarle

2017-09-01

We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties

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Shuyun Wang

2016-01-01

Full Text Available Autologous and nonautologous bone marrow mesenchymal stem/stromal cells (MSCs are being evaluated as proangiogenic agents for ischemic and vascular disease in adults but not in children. A significant number of newborns and infants with critical congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate tissue perfusion. During neonatal cardiac surgery, a small amount of sternal tissue is usually discarded. Here we demonstrate that MSCs can be isolated from human neonatal sternal tissue using a nonenzymatic explant culture method. Neonatal sternal bone MSCs (sbMSCs were clonogenic, had a surface marker expression profile that was characteristic of bone marrow MSCs, were multipotent, and expressed pluripotency-related genes at low levels. Neonatal sbMSCs also demonstrated in vitro proangiogenic properties. Sternal bone MSCs cooperated with human umbilical vein endothelial cells (HUVECs to form 3D networks and tubes in vitro. Conditioned media from sbMSCs cultured in hypoxia also promoted HUVEC survival and migration. Given the neonatal source, ease of isolation, and proangiogenic properties, sbMSCs may have relevance to therapeutic applications.

Nutrition in the prevention of Coronary Heart Disease and the management of lipoprotein disorders

Science.gov (United States)

Cardiovascular disease (CVD) is comprised of coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD). CVD is caused by progressive narrowing and blockage of arteries supplying the heart, brain, and other tissues and organs. CVD is the leading cause of death and disability in our ...

Heart Disease and Stroke in Women

Centers for Disease Control (CDC) Podcasts

2009-05-11

This women's health podcast focuses on the impact of heart disease and stroke in women and includes steps to prevent these conditions.  Created: 5/11/2009 by Office of Women’s Health (OWH) and National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/11/2009.

Do sodium-glucose co-transporter-2 inhibitors prevent heart failure with a preserved ejection fraction by counterbalancing the effects of leptin? A novel hypothesis.

Science.gov (United States)

Packer, Milton

2018-06-01

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin. © 2018 John Wiley & Sons Ltd.

A preliminary study of the relationship between promoter methylation of the ABCG1, GALNT2 and HMGCR genes and coronary heart disease.

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Ping Peng

Full Text Available To investigate the association of ABCG1, GALNT2 and HMGCR genes promoter DNA methylation with coronary heart disease (CHD and explore the interaction between their methylation status and the CHD patients' clinical characteristics in Han Chinese population.Methylation-specific polymerase chain reaction (MSP technology was used to examine the role of the aberrant gene promoter methylation in CHD in Han Chinese population. A total of 85 CHD patients and 54 participants without CHD confirmed by angiography were recruited. 82.8% of the participants with ABCG1 gene promoter hypermethylation have CHD, while only 17.4% of the participants without hypermethylation have it. The average age of the participants with GALNT2 gene promoter hypermethylation is 62.10 ± 8.21, while that of the participants without hypermethylation is 57.28 ± 9.87; in the former group, 75.4% of the participants have CHD, compared to only 50% in the latter group. As for the HMGCR gene, the average age of the participants with promoter hypermethylation is 63.24 ± 8.10 and that of the participants without hypermethylation is 57.79 ± 9.55; its promoter hypermethylation is likely to be related to smoking. Our results indicated a significant statistical association of promoter methylation of the ABCG1 gene with increased risk of CHD (OR = 19.966; 95% CI, 7.319-54.468; P*<0.001; P*: adjusted for age, gender, smoking, lipid level, hypertension, and diabetes. Similar results were obtained for that of the GALNT2 gene (OR = 2.978; 95% CI, 1.335-6.646; P* = 0.008, but not of HMGCR gene (OR = 1.388; 95% CI, 0.572-3.371; P*  = 0.469.The present work provides evidence to support the association of promoter DNA methylation status with the risk profile of CHD. Our data indicates that promoter DNA hypermethylation of the ABCG1 and GALNT2 genes, but not the HMGCR gene, is associated with an increased risk of CHD. CHD, smoking and aging are likely to be the important factors influencing DNA

Cardiomyocyte Overexpression of FABP4 Aggravates Pressure Overload-Induced Heart Hypertrophy.

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Ji Zhang

Full Text Available Fatty acid binding protein 4 (FABP4 is a member of the intracellular lipid-binding protein family, responsible for the transportation of fatty acids. It is considered to express mainly in adipose tissues, and be strongly associated with inflammation, obesity, diabetes and cardiovasculardiseases. Here we report that FABP4 is also expressed in cardiomyocytes and plays an important role in regulating heart function under pressure overload. We generated heart-specific transgenic FABP4 (FABP4-TG mice using α myosin-heavy chain (α-MHC promoter and human FABP4 sequence, resulting in over-expression of FABP4 in cardiomyocytes. The FABP4-TG mice displayed normal cardiac morphology and contractile function. When they were subjected to the transverse aorta constriction (TAC procedure, the FABP4-TG mice developed more cardiac hypertrophy correlated with significantly increased ERK phosphorylation, compared with wild type controls. FABP4 over-expression in cardiomyocytes activated phosphor-ERK signal and up-regulate the expression of cardiac hypertrophic marker genes. Conversely, FABP4 induced phosphor-ERK signal and hypertrophic gene expressions can be markedly inhibited by an ERK inhibitor PD098059 as well as the FABP4 inhibitor BMS309403. These results suggest that FABP4 over-expression in cardiomyocytes can aggravate the development of cardiac hypertrophy through the activation of ERK signal pathway.

Dynamics and distribution of /sup 3/H-dopamine in serum and tissues of heart, brain and adrenal glands of rats with endotoxic shock

Energy Technology Data Exchange (ETDEWEB)

Rainov, A; Boschkov, B; Nikolov, N [Meditsinska Akademiya, Sofia (Bulgaria)

1980-04-01

The dynamics and the distribution of /sup 3/H-dopamine in the serum and tissues of the heart, hypothalamus, cerebral cortex and adrenal glands were studied in 60 Wistar rats. The rats received intravenously 7.4 MBq /sup 3/H-dopamine/kg body weight 10 minutes before they were killed. The experimental animals were subjected to endotoxic shock by injecting them with 2 mg endotoxin of E. coli O 111:B/sub 4//kg body weight, and killed after 5, 10, 15, 20 and 30 min, respectively. Maximum increase of the tritium activity in the organs investigated was observed 20 min after the shock.

Activation of peroxisome proliferator-activated receptor-alpha and -gamma in auricular tissue from heart failure patients.

Science.gov (United States)

Gómez-Garre, Dulcenombre; Herraíz, Marta; González-Rubio, Ma Luisa; Bernal, Rosa; Aragoncillo, Paloma; Carbonell, Amparo; Rufilanchas, Juan José; Fernández-Cruz, Arturo

2006-03-01

Peroxisome proliferator-activated receptors (PPARs), key transcriptional regulators of lipid and energy metabolism in cardiomyocytes, have recently been proposed to modulate cardiovascular pathophysiological responses in experimental models. However, there is little information about the functional activity of PPARs in human heart failure. To investigate PPAR-alpha and -gamma expression and activity, and the association with ET-1 production and fibrosis, in cardiac biopsies from patients with end-stage heart failure due to ischemic cardiomyopathy (ICM) in comparison and from non-failing donor hearts. All samples were obtained during cardiac transplantation. Morphological analysis (by Masson trichrome and image analysis) did not detect fibrosis in the left atrium from non-failing donors (NFLA) or from ICM patients (FLA). However, left ventricles from failing hearts (FLV) contained a greater number of fibrotic areas (NFLA: 3.21+/-1.15, FLA: 1.63+/-0.83, FLV: 14.5+/-3.45%; n = 9, PPPAP-gamma mRNA (by RT-PCR) and protein (by Western blot) levels were higher in the ventricles from failing hearts compared with the atrium from failing and non-failing hearts. Electrophoretic mobility shift assays showed that PPAR-alpha and PPAP-gamma were not activated in the ventricles (NFLA: 1.00+/-0.11, FLA: 1.89+/-0.24, FLV: 0.95+/-0.07; n = 9, PPPAP-gamma are selectively activated in the atria from ICM patients and might be functionally important in the maintenance of atrial morphology.

Adipose tissue as an endocrine organ.

Science.gov (United States)

McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

2014-02-01

Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

ENDURANCE TRAINING AND GLUTATHIONE-DEPENDENT ANTIOXIDANT DEFENSE MECHANISM IN HEART OF THE DIABETIC RATS

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Mustafa Atalay

2003-06-01

Full Text Available Regular physical exercise beneficially influences cardiac antioxidant defenses in normal rats. The aim of this study was to test whether endurance training can strengthen glutathione-dependent antioxidant defense mechanism and decrease lipid peroxidation in heart of the streptozotocin-induced diabetic rats. Redox status of glutathione in blood of diabetic rats in response to training and acute exercise was also examined. Eight weeks of treadmill training increased the endurance in streptozotocin-induced diabetic rats. It did not affect glutathione level in heart tissue at rest and also after exercise. On the other hand, endurance training decreased glutathione peroxidase activity in heart, while glutathione reductase and glutathione S-transferase activities were not affected either by acute exhaustive exercise or endurance training. Reduced and oxidized glutathione levels in blood were not affected by either training or acute exercise. Conjugated dienes levels in heart tissue were increased by acute exhaustive exercise and also 8 weeks treadmill training. Longer duration of exhaustion in trained group may have contributed to the increased conjugated dienes levels in heart after acute exercise. Our results suggest that endurance type exercise may make heart more susceptible to oxidative stress. Therefore it may be wise to combine aerobic exercise with insulin treatment to prevent its adverse effects on antioxidant defense in heart in patients with diabetes mellitus

Omega-3 Polyunsaturated Fatty Acids and Heart Rate Variability

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Jeppe Hagstrup Christensen

2011-11-01

Full Text Available Omega-3 polyunsaturated fatty acids (PUFA may modulate autonomic control of the heart because omega-3 PUFA is abundant in the brain and other nervous tissue as well as in cardiac tissue. This might partly explain why omega-3 PUFA offer some protection against sudden cardiac death (SCD. The autonomic nervous system is involved in the pathogenesis of SCD. Heart rate variability (HRV can be used as a non-invasive marker of cardiac autonomic control and a low HRV is a predictor for SCD and arrhythmic events. Studies on HRV and omega-3 PUFA have been performed in several populations such as patients with ischemic heart disease, patients with diabetes mellitus, patients with chronic renal failure, and in healthy subjects as well as in children.. The studies have demonstrated a positive association between cellular content of omega-3 PUFA and HRV and supplementation with omega-3 PUFA seems to increase HRV which could be a possible explanation for decreased risk of arrhythmic events and SCD sometimes observed after omega-3 PUFA supplementation. However, the results are not consistent and further research is needed

Advantages and Limitations of Direct PCR Amplification of Bacterial 16S-rDNA from Resected Heart Tissue or Swabs Followed by Direct Sequencing for Diagnosing Infective Endocarditis: A Retrospective Analysis in the Routine Clinical Setting

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Daniela Maneg

2016-01-01

Full Text Available Infective endocarditis (IE is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5% with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke’s diagnostic classification scheme.

Engineering Complex Tissues

Science.gov (United States)

MIKOS, ANTONIOS G.; HERRING, SUSAN W.; OCHAREON, PANNEE; ELISSEEFF, JENNIFER; LU, HELEN H.; KANDEL, RITA; SCHOEN, FREDERICK J.; TONER, MEHMET; MOONEY, DAVID; ATALA, ANTHONY; VAN DYKE, MARK E.; KAPLAN, DAVID; VUNJAK-NOVAKOVIC, GORDANA

2010-01-01

This article summarizes the views expressed at the third session of the workshop “Tissue Engineering—The Next Generation,” which was devoted to the engineering of complex tissue structures. Antonios Mikos described the engineering of complex oral and craniofacial tissues as a “guided interplay” between biomaterial scaffolds, growth factors, and local cell populations toward the restoration of the original architecture and function of complex tissues. Susan Herring, reviewing osteogenesis and vasculogenesis, explained that the vascular arrangement precedes and dictates the architecture of the new bone, and proposed that engineering of osseous tissues might benefit from preconstruction of an appropriate vasculature. Jennifer Elisseeff explored the formation of complex tissue structures based on the example of stratified cartilage engineered using stem cells and hydrogels. Helen Lu discussed engineering of tissue interfaces, a problem critical for biological fixation of tendons and ligaments, and the development of a new generation of fixation devices. Rita Kandel discussed the challenges related to the re-creation of the cartilage-bone interface, in the context of tissue engineered joint repair. Frederick Schoen emphasized, in the context of heart valve engineering, the need for including the requirements derived from “adult biology” of tissue remodeling and establishing reliable early predictors of success or failure of tissue engineered implants. Mehmet Toner presented a review of biopreservation techniques and stressed that a new breakthrough in this field may be necessary to meet all the needs of tissue engineering. David Mooney described systems providing temporal and spatial regulation of growth factor availability, which may find utility in virtually all tissue engineering and regeneration applications, including directed in vitro and in vivo vascularization of tissues. Anthony Atala offered a clinician’s perspective for functional tissue

Life-long preservation of the regenerative capacity in the fin and heart in zebrafish

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Junji Itou

2012-06-01

The zebrafish is a widely used model animal to study the regeneration of organs, such as the fin and heart. Their average lifetime is about 3 years, and recent studies have shown that zebrafish exhibit aging-related degeneration, suggesting the possibility that aging might affect regenerative potential. In order to investigate this possibility, we compared regeneration of the fin and heart after experimental amputation in young (6–12 month old and old (26–36 month old fish. Comparison of recovery rate of the caudal fin, measured every two or three days from one day post amputation until 13 days post amputation, show that fins in young and old fish regenerate at a similar rate. In the heart, myocardium regeneration and cardiomyocyte proliferation occurred similarly in the two groups. Moreover, neo-vascularization, as well as activation of fibroblast growth factor signaling, which is required for neo-vascularization, occurred similarly. The epicardial tissue is a thin layer tissue that covers the heart, and starts to express several genes immediately in response to injury. The expression of epicardial genes, such as wt1b and aldh1a2, in response to heart injury was comparable in two groups. Our results demonstrate that zebrafish preserve a life-long regenerative ability of the caudal fin and heart.

Utilizing a Collaborative Learning Model to Promote Early Extubation Following Infant Heart Surgery.

Science.gov (United States)

Mahle, William T; Nicolson, Susan C; Hollenbeck-Pringle, Danielle; Gaies, Michael G; Witte, Madolin K; Lee, Eva K; Goldsworthy, Michelle; Stark, Paul C; Burns, Kristin M; Scheurer, Mark A; Cooper, David S; Thiagarajan, Ravi; Sivarajan, V Ben; Colan, Steven D; Schamberger, Marcus S; Shekerdemian, Lara S

2016-10-01

To determine whether a collaborative learning strategy-derived clinical practice guideline can reduce the duration of endotracheal intubation following infant heart surgery. Prospective and retrospective data collected from the Pediatric Heart Network in the 12 months pre- and post-clinical practice guideline implementation at the four sites participating in the collaborative (active sites) compared with data from five Pediatric Heart Network centers not participating in collaborative learning (control sites). Ten children's hospitals. Data were collected for infants following two-index operations: 1) repair of isolated coarctation of the aorta (birth to 365 d) and 2) repair of tetralogy of Fallot (29-365 d). There were 240 subjects eligible for the clinical practice guideline at active sites and 259 subjects at control sites. Development and application of early extubation clinical practice guideline. After clinical practice guideline implementation, the rate of early extubation at active sites increased significantly from 11.7% to 66.9% (p collaborative learning strategy designed clinical practice guideline significantly increased the rate of early extubation with no change in the rate of reintubation. The early extubation clinical practice guideline did not significantly change postoperative ICU length of stay.

Perceptions of risk of coronary heart disease among people living with type 2 diabetes mellitus.

Science.gov (United States)

Ammouri, Ali Ahmad; Abu Raddaha, Ahmad H; Natarajan, Jansi; D'Souza, Melba Sheila

2018-02-01

Our aim is to assess perception of risk of developing coronary heart disease and to examine its associations with individuals' characteristics and health behaviours among Omani people with type 2 diabetes mellitus (T2DM). Evaluating perceptions of being at risk of developing a disease may give insight into health promotion behaviours. People with diabetes are at high risk of coronary heart disease. The management of diabetes mellitus should include prevention and control of coronary heart disease. A cross-sectional correlational study was conducted. A convenience sample of 160 adults with T2DM was invited to participate in this study between November 2014 and March 2015. Descriptive and regression analyses were performed to examine associations between study variables. Perception of risk of developing coronary heart disease was significantly associated with low educational level (β = 0.191, P diabetes mellitus (β = 0.200, P healthy diet more frequently. Teaching people with T2DM about the risk of developing coronary heart disease is essential as it could motivate them to perform health promotion behaviours, which may assist in controlling and reducing coronary heart disease. © 2017 John Wiley & Sons Australia, Ltd.

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit

Science.gov (United States)

Nikolaidou, Theodora; Cai, Xue J.; Stephenson, Robert S.; Yanni, Joseph; Lowe, Tristan; Atkinson, Andrew J.; Jones, Caroline B.; Sardar, Rida; Corno, Antonio F.; Dobrzynski, Halina; Withers, Philip J.; Jarvis, Jonathan C.; Hart, George; Boyett, Mark R.

2015-01-01

Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ. PMID:26509807

Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.

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Theodora Nikolaidou

Full Text Available Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ. Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT. Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.

Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease

NARCIS (Netherlands)

Keliher, Edmund J.; Ye, Yu-Xiang; Wojtkiewicz, Gregory R.; Aguirre, Aaron D.; Tricot, Benoit; Senders, Max L.; Groenen, Hannah; Fay, Francois; Perez-Medina, Carlos; Calcagno, Claudia; Carlucci, Giuseppe; Reiner, Thomas; Sun, Yuan; Courties, Gabriel; Iwamoto, Yoshiko; Kim, Hye-Yeong; Wang, Cuihua; Chen, John W.; Swirski, Filip K.; Wey, Hsiao-Ying; Hooker, Jacob; Fayad, Zahi A.; Mulder, Willem J. M.; Weissleder, Ralph; Nahrendorf, Matthias

2017-01-01

Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission

Injection resorbable polymer shells for soft tissue augmentation

CSIR Research Space (South Africa)

Naidoo, Kersch

2008-11-01

Full Text Available CSIR researchers have developed an injectable, resorbable soft tissue bulking product that has potential applications in fields ranging from heart and recontructive surgery, to minimally invasive cosmetic surgery. Biomaterials research is very...

Promoter hypermethylation contributes to frequent inactivation of a putative conditional tumor suppressor gene connective tissue growth factor in ovarian cancer.

Science.gov (United States)

Kikuchi, Ryoko; Tsuda, Hitoshi; Kanai, Yae; Kasamatsu, Takahiro; Sengoku, Kazuo; Hirohashi, Setsuo; Inazawa, Johji; Imoto, Issei

2007-08-01

Connective tissue growth factor (CTGF) is a secreted protein belonging to the CCN family, members of which are implicated in various biological processes. We identified a homozygous loss of CTGF (6q23.2) in the course of screening a panel of ovarian cancer cell lines for genomic copy number aberrations using in-house array-based comparative genomic hybridization. CTGF mRNA expression was observed in normal ovarian tissue and immortalized ovarian epithelial cells but was reduced in many ovarian cancer cell lines without its homozygous deletion (12 of 23 lines) and restored after treatment with 5-aza 2'-deoxycytidine. The methylation status around the CTGF CpG island correlated inversely with the expression, and a putative target region for methylation showed promoter activity. CTGF methylation was frequently observed in primary ovarian cancer tissues (39 of 66, 59%) and inversely correlated with CTGF mRNA expression. In an immunohistochemical analysis of primary ovarian cancers, CTGF protein expression was frequently reduced (84 of 103 cases, 82%). Ovarian cancer tended to lack CTGF expression more frequently in the earlier stages (stages I and II) than the advanced stages (stages III and IV). CTGF protein was also differentially expressed among histologic subtypes. Exogenous restoration of CTGF expression or treatment with recombinant CTGF inhibited the growth of ovarian cancer cells lacking its expression, whereas knockdown of endogenous CTGF accelerated growth of ovarian cancer cells with expression of this gene. These results suggest that epigenetic silencing by hypermethylation of the CTGF promoter leads to a loss of CTGF function, which may be a factor in the carcinogenesis of ovarian cancer in a stage-dependent and/or histologic subtype-dependent manner.

Cardiomyocytes from late embryos and neonates do optimal work and striate best on substrates with tissue-level elasticity: metrics and mathematics.

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Majkut, Stephanie F; Discher, Dennis E

2012-11-01

In this review, we discuss recent studies on the mechanosensitive morphology and function of cardiomyocytes derived from embryos and neonates. For early cardiomyocytes cultured on substrates of various stiffnesses, contractile function as measured by force production, work output and calcium handling is optimized when the culture substrate stiffness mimics that of the tissue from which the cells were obtained. This optimal contractile function corresponds to changes in sarcomeric protein conformation and organization that promote contractile ability. In light of current models for myofibillogenesis, a recent mathematical model of striation and alignment on elastic substrates helps to illuminate how substrate stiffness modulates early myofibril formation and organization. During embryonic heart formation and maturation, cardiac tissue mechanics change dynamically. Experiments and models highlighted here have important implications for understanding cardiomyocyte differentiation and function in development and perhaps in regeneration processes.

Assessment of sustained effects of levosimendan and dobutamine on left ventricular systolic functions by using novel tissue Doppler derived indices in patients with advanced heart failure.

Science.gov (United States)

Oner, Ender; Erturk, Mehmet; Birant, Ali; Kurtar Mansıroglu, Aslı; Akturk, Ibrahim Faruk; Karakurt, Huseyin; Yalcin, Ahmet Arif; Uzun, Fatih; Somuncu, Mustafa Umut; Yildirim, Aydin

2015-01-01

Previous studies comparing levosimendan vs. dobutamine have revealed that levosimendan is better in relieving symptoms. Echocardiographic studies have been done using second measurements immediately following a dobutamine infusion or while it was still being administered. The aim of our study was assessment of sustained effects of 24 h levosimendan and dobutamine infusions on left ventricular systolic functions. A total of 61 patients with acutely decompensated heart failure with New York Heart Association (NYHA) class III or IV symptoms were randomized to receive either levosimendan or dobutamine 2:1 in an open label fashion. Before and 5 days after the initiation of infusions, functional class was assessed, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fraction (LVEF), mitral inflow peak E and A wave velocity, and E/A ratios were measured; using tissue Doppler imaging, isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), early (E') and late (A') diastolic velocities, and E'/A' and E/E' ratios were measured. The NYHA class improved in both groups, but improvements were prominent in the levosimendan group. NT-proBNP levels were significantly reduced in the levosimendan group. Improvements in LVEF and diastolic indices were significant in the levosimendan group. Tissue Doppler-derived systolic indices of IVV and IVA increased significantly in the levosimendan group. Improvements in left ventricular systolic and diastolic functions continue after a levosimendan infusion.

Nuclear triiodothyronine receptors in rabbit heart

International Nuclear Information System (INIS)

Banerjee, S.K.; Ulrich, J.M.; Kaldor, G.J.

1986-01-01

Nuclear triiodothyronine receptors from rat liver have been characterized in detail by several investigators. However, little work has been done in this area using heart tissue. In this study they examined and characterized the triiodothyronine binding in rabbit hearts. Nuclei have been prepared from ventricular muscle cells of normal and thyrotoxic rabbits as well as from atrial muscle cells of normal rabbit. Hearts were perfused with a minimum essential medium containing collagenase and bovine serum albumin. Myocardial cells were isolated and then disrupted by sonication and washing with a Triton X-100 buffer solution. A discontinuous sucrose density gradient was then used to isolate the mycoardial nuclei. Radiolabelled triiodothyronine (T 3 ) binding to nuclei was examined using conditions described by established procedures. Scatchard analysis of the binding data yields maximum binding capacity (B/sub max/) of 0.17 +/- 0.2 pmol/mg DNA and apparent dissociation constant (K/sub d/) of 400 +/- 50 pM for normal heart T 3 -receptors. The apparent capacity for T 3 binding is approximately 40% greater in myocardial nuclei prepared from hearts of hyperthyroid rabbits. The binding capacity of atrial muscle nuclei is about fourfold lower than ventricular cell nuclei. The results suggest that binding capacity for T 3 -receptor in the atrium is considerably lower than that found in the ventricle

Thyroid hormone action in postnatal heart development

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Ming Li

2014-11-01

Full Text Available Thyroid hormone is a critical regulator of cardiac growth and development, both in fetal life and postnatally. Here we review the role of thyroid hormone in postnatal cardiac development, given recent insights into its role in stimulating a burst of cardiomyocyte proliferation in the murine heart in preadolescence; a response required to meet the massive increase in circulatory demand predicated by an almost quadrupling of body weight during a period of about 21 days from birth to adolescence. Importantly, thyroid hormone metabolism is altered by chronic diseases, such as heart failure and ischemic heart disease, as well as in very sick children requiring surgery for congenital heart diseases, which results in low T3 syndrome that impairs cardiovascular function and is associated with a poor prognosis. Therapy with T3 or thyroid hormone analogs has been shown to improve cardiac contractility; however, the mechanism is as yet unknown. Given the postnatal cardiomyocyte mitogenic potential of T3, its ability to enhance cardiac function by promoting cardiomyocyte proliferation warrants further consideration.

Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

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Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

2015-06-01

Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation

Valvular Heart Disease in Heart Failure

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Giuseppe MC Rosano

2017-01-01

Full Text Available Structural valvular heart disease may be the cause of heart failure or may worsen the clinical status of patients with heart failure. Heart failure may also develop in patients treated with valve surgery. Patients with heart failure with valvular heart disease are at increased risk of events including sudden cardiac death. Before considering intervention (surgical or percutaneous all patients should receive appropriate medical and device therapy taking into account that vasodilators must be used with caution in patients with severe aortic stenosis. Numerous percutaneous and/or hybrid procedures have been introduced in the past few years and they are changing the management of valvular heart disease. In patients with heart failure and valvular heart disease, either primary or functional, the whole process of decision-making should be staged through a comprehensive evaluation of the risk– benefit ratio of different treatment strategies and should be made by a multidisciplinary ‘heart team’ with a particular expertise in valvular heart disease. The heart team should include heart failure cardiologists, cardiac surgeons/structural valve interventionists, imaging specialists, anaesthetists, geriatricians and intensive care specialists. This article will review recent developments and distill practical guidance in the management of this important heart failure co-morbidity.

Promoting heart health: an HBCU collaboration with the Living Heart Foundation and the National Football League Retired Players Association.

Science.gov (United States)

Valentine, Peggy; Duren-Winfield, Vanessa; Onsomu, Elijah O; Hoover, Eddie L; Cammock, Cheryl E; Roberts, Arthur

2012-01-01

Cardiovascular disease continues to be the leading cause of death in the United States and African Americans are disproportionately affected. Cardiovascular disease risk factors such as obesity, hypertension, family history of heart disease, and physical inactivity are often higher in African American young adults. The aim of the current study was to assess cardiovascular disease risk factors at a historically black college and university (HBCU) in North Carolina. A collaborative partnership was established that included Living Heart Foundation, the NFL Retired Players Association and a HBCU. Ninety-one students (77 females and 14 males) aged 18 to 55 years (mean, 24 y, SD = 9 y) were recruited via dissemination of flyers, brochures, mass e-mailing, and announcements. Demographic and medical history data were collected. Stata version 10.1 was used for all analyses. Fifty-three percent of the participants reported having experienced a chronic health condition, 32% were overweight (body mass index [BMI], 25-29.9 kg/m2) and 31% obese (BMI > or = 30 kg/m2). Five percent of females and 23% of males had high-density lipoprotein cholesterol of 40 mg/dL or less, indicative of a risk for developing heart disease. There is an urgent need to intervene among African American college students and address behavioral risk factors for cardiovascular disease. Such interventions may have a major impact on their overall and future health outcomes. Strategies to be employed need to focus on the integration of culturally appropriate healthy lifestyle programs into the curriculum and university health centers. Consultations with stakeholders for ideas and resources should be encouraged.

Composing a Tumor Specific Bacterial Promoter.

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Igor V Deyneko

Full Text Available Systemically applied Salmonella enterica spp. have been shown to invade and colonize neoplastic tissues where it retards the growth of many tumors. This offers the possibility to use the bacteria as a vehicle for the tumor specific delivery of therapeutic molecules. Specificity of such delivery is solely depending on promoter sequences that control the production of a target molecule. We have established the functional structure of bacterial promoters that are transcriptionally active exclusively in tumor tissues after systemic application. We observed that the specific transcriptional activation is accomplished by a combination of a weak basal promoter and a strong FNR binding site. This represents a minimal set of control elements required for such activation. In natural promoters, additional DNA remodeling elements are found that alter the level of transcription quantitatively. Inefficiency of the basal promoter ensures the absence of transcription outside tumors. As a proof of concept, we compiled an artificial promoter sequence from individual motifs representing FNR and basal promoter and showed specific activation in a tumor microenvironment. Our results open possibilities for the generation of promoters with an adjusted level of expression of target proteins in particular for applications in bacterial tumor therapy.

FOXO1 expression in keratinocytes promotes connective tissue healing

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Zhang, Chenying; Lim, Jason; Liu, Jian; Ponugoti, Bhaskar; Alsadun, Sarah; Tian, Chen; Vafa, Rameen; Graves, Dana T.

2017-01-01

Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome. PMID:28220813

Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

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Lia Millucci

2014-01-01

Full Text Available Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart.

Amyloidosis, Inflammation, and Oxidative Stress in the Heart of an Alkaptonuric Patient

Science.gov (United States)

Ghezzi, Lorenzo; Giorgetti, Giovanna; Viti, Cecilia; Geminiani, Michela; Soldani, Patrizia; Lupetti, Pietro; Benvenuti, Chiara; Perfetto, Federico; Spreafico, Adriano; Santucci, Annalisa

2014-01-01

Background. Alkaptonuria, a rare autosomal recessive metabolic disorder caused by deficiency in homogentisate 1,2-dioxygenase activity, leads to accumulation of oxidised homogentisic acid in cartilage and collagenous structures present in all organs and tissues, especially joints and heart, causing a pigmentation called ochronosis. A secondary amyloidosis is associated with AKU. Here we report a study of an aortic valve from an AKU patient. Results. Congo Red birefringence, Th-T fluorescence, and biochemical assays demonstrated the presence of SAA-amyloid deposits in AKU stenotic aortic valve. Light and electron microscopy assessed the colocalization of ochronotic pigment and SAA-amyloid, the presence of calcified areas in the valve. Immunofluorescence detected lipid peroxidation of the tissue and lymphocyte/macrophage infiltration causing inflammation. High SAA plasma levels and proinflammatory cytokines levels comparable to those from rheumatoid arthritis patients were found in AKU patient. Conclusions. SAA-amyloidosis was present in the aortic valve from an AKU patient and colocalized with ochronotic pigment as well as with tissue calcification, lipid oxidation, macrophages infiltration, cell death, and tissue degeneration. A local HGD expression in human cardiac tissue has also been ascertained suggesting a consequent local production of ochronotic pigment in AKU heart. PMID:24876668

Emerging hemodynamic signatures of the right heart (Third International Right Heart Failure Summit, part 2)

OpenAIRE

Maron, Bradley A.

2014-01-01

Abstract Despite the importance of preserved right ventricular structure and function with respect to outcome across the spectrum of lung, cardiac, and pulmonary vascular diseases, only recently have organized efforts developed to consider the pulmonary vascular–right ventricular apparatus as a specific unit within the larger context of cardiopulmonary pathophysiology. The Third International Right Heart Failure Summit (Boston, MA) was a multidisciplinary event dedicated to promoting a dialog...

Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat

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