摘要
成人心肌保护、更新或恢复本身的能力有限。局部微环境可诱导表观遗传变化从而影响休息期心肌细胞的存活、增殖、功能和衰老和并受到不同的压力。细胞微环境的特点是反应离子的释放,氧自由基、自主/旁分泌因子和通过特定的激活子的相互作用驱动基因重组的RNAs。表观遗传变化可能在转录和转录后水平,并改变心脏的生理特征。 异常DNA甲基化是逐步衰减的收缩功能和血管生成能力的原因;同时,组蛋白乙酰化作用促进在缺血性微环境心肌细胞的存活、功能和增殖。至少,MicroRNA的表达和分泌以及长非编码RNA可能调节成人心肌细胞压力的阈值,也能诱导基质代谢。天然或合成活性化合物有效调节心肌细胞的表观遗传状态。植物性食物含有很多具有表观遗传属性的活性化合物可能对心脏活力恢复的研发有临床意义。本文我们回顾了新的巩固心肌重构的表观遗传机制,修复/再生或衰老都是为了支持成年人心脏最有效的和可再生救援治疗的发展。
关键词: 衰老,心肌重构,表观遗传学,心力衰竭,心肌再生,天然化合物
Current Drug Targets
Title:Epigenetic Regulation of Myocardial Homeostasis, Self-Regeneration and Senescence
Volume: 16 Issue: 8
关键词: 衰老,心肌重构,表观遗传学,心力衰竭,心肌再生,天然化合物
摘要: 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.
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Epigenetic Regulation of Myocardial Homeostasis, Self-Regeneration and Senescence, Current Drug Targets 2015; 16 (8) . https://dx.doi.org/10.2174/1389450116666150630110821
DOI https://dx.doi.org/10.2174/1389450116666150630110821 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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