Department of Diabetes Complications and Metabolism, Beckman Research Institute of City of Hope, Duarte, California, USA.
Curr Opin Cardiol. 2020 May;35(3):234-241. doi: 10.1097/HCO.0000000000000728.
Hyperlipidemia, hypertension, diabetes and related metabolic disorders increase the risk for cardiovascular disease (CVD). Despite significant progress in the identification of key mechanisms and genetic polymorphisms linked to various CVDs, the rates of CVDs continue to escalate, underscoring the need to evaluate additional mechanisms for more effective therapies. Environment and lifestyle changes can alter epigenetic mechanisms mediated by histone modifications and long noncoding RNAs (lncRNAs) which play important roles in gene regulation. The review summarizes recent findings on the role of epigenetic mechanisms in CVD.
Recent studies identified dysregulated histone modifications and chromatin modifying proteins at cis-regulatory elements, including enhancers/super-enhancers, mediating the expression of genes associated with CVD in vascular and immune cells in response to growth factors and inflammatory mediators. Several lncRNAs have also been reported to contribute to pathological gene expression via cis and trans mechanisms involving interactions with nuclear proteins, co-operation with enhancers/super enhancers and acting as microRNA sponges.
Epigenomic approaches in cells affected in CVDs can be exploited to understand the function of genetic polymorphisms at cis-regulatory elements and crosstalk between enhancers and lncRNAs associated with disease susceptibility and progression. The reversible nature of epigenetics provides opportunities for the development of novel therapeutic strategies for CVD.
高脂血症、高血压、糖尿病和相关代谢紊乱会增加心血管疾病（CVD）的风险。尽管在确定与各种 CVD 相关的关键机制和遗传多态性方面取得了重大进展，但 CVD 的发病率仍在不断上升，这表明需要评估其他机制以实现更有效的治疗。环境和生活方式的改变可以改变组蛋白修饰和长链非编码 RNA（lncRNA）介导的表观遗传机制，这些机制在基因调控中发挥着重要作用。本文综述了表观遗传机制在 CVD 中的作用的最新研究发现。
最近的研究发现，血管和免疫细胞中的顺式调控元件（包括增强子/超级增强子）中的组蛋白修饰和染色质修饰蛋白失调，这些元件介导与 CVD 相关的基因表达，这些基因对生长因子和炎症介质有反应。据报道，一些 lncRNA 还通过涉及与核蛋白相互作用、与增强子/超级增强子合作以及作为 microRNA 海绵的顺式和反式机制，导致病理性基因表达。
可以利用 CVD 相关细胞中的表观基因组方法来了解顺式调控元件中遗传多态性的功能以及与疾病易感性和进展相关的增强子和 lncRNA 之间的串扰。表观遗传的可逆性为 CVD 的新型治疗策略的发展提供了机会。
