Division of Pharmacology and Physiology, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Center for Genomics, Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA 92350, USA.
Int J Mol Sci. 2018 Apr 12;19(4):1174. doi: 10.3390/ijms19041174.
Systemic hypertension, which eventually results in heart failure, renal failure or stroke, is a common chronic human disorder that particularly affects elders. Although many signaling pathways involved in the development of hypertension have been reported over the past decades, which has led to the implementation of a wide variety of anti-hypertensive therapies, one half of all hypertensive patients still do not have their blood pressure controlled. The frontier in understanding the molecular mechanisms underlying hypertension has now advanced to the level of epigenomics. Particularly, increasing evidence is emerging that DNA methylation and histone modifications play an important role in gene regulation and are involved in alteration of the phenotype and function of vascular cells in response to environmental stresses. This review seeks to highlight the recent advances in our knowledge of the epigenetic regulations and mechanisms of hypertension, focusing on the role of DNA methylation and histone modification in the vascular wall. A better understanding of the epigenomic regulation in the hypertensive vessel may lead to the identification of novel target molecules that, in turn, may lead to novel drug discoveries for the treatment of hypertension.
系统性高血压最终会导致心力衰竭、肾衰竭或中风,是一种常见的慢性人类疾病,尤其影响老年人。尽管在过去几十年中已经报道了许多参与高血压发展的信号通路,这导致了广泛的抗高血压治疗方法的实施,但仍有一半的高血压患者的血压没有得到控制。理解高血压分子机制的前沿现在已经发展到表观基因组学的水平。特别是,越来越多的证据表明,DNA 甲基化和组蛋白修饰在基因调控中发挥重要作用,并参与血管细胞表型和功能的改变,以应对环境压力。本文综述了我们对高血压表观遗传调控和机制的最新认识,重点关注 DNA 甲基化和组蛋白修饰在血管壁中的作用。对高血压血管中表观基因组调控的更好理解可能会导致鉴定出新的靶分子,从而可能为高血压的治疗发现新的药物。