Fraineau Sylvain, Palii Carmen G, Allan David S, Brand Marjorie
Sprott Center for Stem Cell Research, Regenerative Medicine Program, Ottawa Hospital Research Institute, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Canada; Ottawa Institute of Systems Biology, Canada.
FEBS J. 2015 May;282(9):1605-29. doi: 10.1111/febs.13183. Epub 2015 Jan 14.
Maintenance of vascular integrity is essential for the prevention of vascular disease and for recovery following cardiovascular, cerebrovascular and peripheral vascular events including limb ischemia, heart attack and stroke. Endothelial stem/progenitor cells have recently gained considerable interest due to their potential use in stem cell therapies to mediate revascularization after ischemic injury. Therefore, there is an urgent need to understand fundamental mechanisms regulating vascular repair in specific cell types to develop new beneficial therapeutic interventions. In this review, we highlight recent studies demonstrating that epigenetic mechanisms (including post-translational modifications of DNA and histones as well as non-coding RNA-mediated processes) play essential roles in the regulation of endothelial stem/progenitor cell functions through modifying chromatin structure. Furthermore, we discuss the potential of using small molecules that modulate the activities of epigenetic enzymes to enhance the vascular repair function of endothelial cells and offer insight on potential strategies that may accelerate clinical applications.
维持血管完整性对于预防血管疾病以及心血管、脑血管和外周血管事件(包括肢体缺血、心脏病发作和中风)后的恢复至关重要。内皮干/祖细胞因其在干细胞疗法中用于介导缺血性损伤后血管再生的潜在用途,最近引起了广泛关注。因此,迫切需要了解调节特定细胞类型中血管修复的基本机制,以开发新的有益治疗干预措施。在本综述中,我们重点介绍了最近的研究,这些研究表明表观遗传机制(包括DNA和组蛋白的翻译后修饰以及非编码RNA介导的过程)通过修饰染色质结构在调节内皮干/祖细胞功能中起重要作用。此外,我们讨论了使用调节表观遗传酶活性的小分子来增强内皮细胞血管修复功能的潜力,并对可能加速临床应用的潜在策略提供见解。