1,721,104 research outputs found
MiR-21 and cardiac fibrosis. Another brick in the wall?
No full textOrgan fibrosis is a common final pathway of long-lasting and iterative tissue fibrosis, and is present in several pathologies, including ischaemic heart disease, diabetes mellitus, hypertension, and chronic kidney disease. Thus, it represents a widespread cause of morbidity and mortality. Tissue fibrosis is characterized by an excessive and uncontrolled deposition of extracellular matrix (ECM) elements. The development of fibrosis requires: (i) increased synthesis by matrix metalloproteinases (MMPs) and decreased degradation of ECM due to down-regulation of MMP inhibitors; (ii) the stimulation of profibrotic mediators, such as transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and cytokines; (iii) the differentiation of fibroblasts into myofibroblasts, which express features of smooth muscle differentiation; and (iv) the recruitment of cells of an endothelial origin for endothelial to mesenchymal transition (EndMT), generating cells that still express endothelial markers while gaining fibroblast-like characteristics. In addition, innate and adaptive immune responses play an important role in development of fibrosis. Despite recent advances in the understanding of the mechanisms underlying its development, therapeutic strategies specifically aimed at fibrosis remain limited
Role of the epigenome in heart failure
No full textGene expression is needed for the maintenance of heart function under normal conditions and in response to stress. Each cell type of the heart has a specific program controlling transcription. Different types of stress induce modifications of these programs, and if prolonged, can lead to altered cardiac phenotype and, eventually, to heart failure. The transcriptional status of a gene is regulated by the epigenome, a complex network of DNA and histone modifications. Until a few years ago, our understanding of the role of the epigenome in heart disease was limited to that played by histone deacetylation. But over the last decade, the consequences for the maintenance of homeostasis in the heart and for the development of cardiac hypertrophy of a number of other modifications, including DNA methylation and hydroxymethylation, histone methylation and acetylation, and changes in chromatin architecture, have become better understood. Indeed, it is now clear that many levels of regulation contribute in defining the epigenetic landscape required for correct cardiomyocyte function, and that their perturbation is responsible for cardiac hypertrophy and fibrosis. Here, we review these aspects and draw a picture of what epigenetic modification may imply at the therapeutic level for heart failure
Epigenetics in heart failure
No full textHeart failure is one of the main causes of mortality in developed countries and is frequently associated with cardiac hypertrophy. Gene expression reprogramming in cardiac myocytes is a key feature of heart hypertrophy and failure and is characterized by upregulation of fetal genes and decreased expression of some subsets of adult ones. The full picture of signaling events underlying gene transcription in these pathophysiologic states is not completely understood, but recent evidence suggests a major role for epigenetics. This report provides an overview of the mechanisms of epigenetics and how they affect myocardial gene expression during hypertrophy and failure. © 2010 New York Academy of Sciences
Heart failure: Targeting transcriptional and post-transcriptional control mechanisms of hypertrophy for treatment
No full textRNA (Epi)genetics in cardiovascular diseases
No full textNext-generation sequencing has greatly improved our knowledge of the mammalian transcriptome, identifying thousands of non-coding RNAs (ncRNAs), which are RNAs that rather than translate for proteins, have regulatory functions. Perhaps unsurprisingly, dysregulation of individual ncRNAs has been associated with the development of pathologies, including of the cardiovascular system. The best-characterized group of ncRNAs is represented by the short, highly conserved RNAs named microRNAs (miRNAs). This ncRNA species, which principally exerts an inhibitory action on gene expression, has been implicated in many cardiovascular diseases. Unfortunately, the complexity of action of other types of ncRNA, such as long ncRNAs, has somewhat hampered the study of their role in cardiovascular pathologies. A detailed characterization of the mechanism of action of these different ncRNA species would be conducive to a better understanding of the cellular processes underlying cardiovascular disease and may lead to the development of innovative therapeutic strategies. Here, we give an overview of the current knowledge on the function of ncRNAs and their roles in cardiovascular disease development, concentrating mainly on microRNAs and long ncRNAs
Risk of hospitalization for heart failure in rheumatoid arthritis patients treated with etanercept and abatacept
No full textTo estimate biologic influence on heart failure (HF) risk in rheumatoid arthritis. Retrospective cohort (RECORD Study of Italian Society for Rheumatology) study on administrative healthcare databases. We identified 2527 patients treated with either etanercept (n = 1690) or abatacept (n = 837). HF incidence rate was higher in the abatacept cohort than in the etanercept cohort with a 2.38 (95% CI 1.08–5.27) crude competing risk HR (SHR) for abatacept of developing HF, not confirmed after adjustment for prespecified confounders (SHR 1.43; 95% CI 0.51–3.98). Abatacept, compared to etanercept, is prescribed to patients with a worse cardiovascular profile but does not increase the risk of developing HF, when confounding factors are accounted for
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