Senescence Of Cardiac Cells Research Articles

Epigenetic Regulation of Myocardial Homeostasis, Self-Regeneration and Senescence.

The adult myocardium has limited capacity to preserve, renew or rejuvenate itself. The local microenvironment may induce epigenetic changes affecting the survival, proliferation, function and senescence of cardiac cells at rest and following the exposure to different stressors. The cellular response to microenvironment is characterized by the release of ions, oxygen free radicals, auto/paracrine factors and RNAs that drive the magnitude of gene reprogramming through the interaction with specific promoters. The epigenetic alterations may act at transcriptional and post-transcriptional level and change cardiac physiological traits. The abnormal DNA methylation underlies the progressive decay of contractile function and the angiogenic ability; while, the histone acetylation promotes the survival, function and proliferation of cardiac cells in the presence of ischemic microenvironment. At least, the expression and secretion of microRNAs and long noncoding RNAs may regulate the threshold to stress tolerance of adult cardiac cells and induce the matrix turnover as well. Natural or synthetic active compounds effectively modulate the epigenetic state of cardiac cells. Plant foods contain many active compounds with epigenetic properties and might assume a clinical significance as natural cardiac regenerators or rejuvenators. Our review describes novel epigenetic mechanisms that underpin myocardial remodeling, repair/ regeneration or senescence in order to support the development of most effective and reproducible rescue therapy of adult heart.

Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration

An emerging aspect of redox signaling is the pathway mediated by electrophilic byproducts, such as nitrated cyclic nucleotide (for example, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP)) and nitro or keto derivatives of unsaturated fatty acids, generated via reactions of inflammation-related enzymes, reactive oxygen species, nitric oxide and secondary products. Here we report that enzymatically generated hydrogen sulfide anion (HS(-)) regulates the metabolism and signaling actions of various electrophiles. HS(-) reacts with electrophiles, best represented by 8-nitro-cGMP, via direct sulfhydration and modulates cellular redox signaling. The relevance of this reaction is reinforced by the significant 8-nitro-cGMP formation in mouse cardiac tissue after myocardial infarction that is modulated by alterations in HS(-) biosynthesis. Cardiac HS(-), in turn, suppresses electrophile-mediated H-Ras activation and cardiac cell senescence, contributing to the beneficial effects of HS(-) on myocardial infarction-associated heart failure. Thus, this study reveals HS(-)-induced electrophile sulfhydration as a unique mechanism for regulating electrophile-mediated redox signaling.