Epigenetic Regulation of the Renin-Angiotensin-Aldosterone System in Hypertension.

Activation of the renin-angiotensin-aldosterone system (RAAS) plays an important pathophysiological role in hypertension. Increased mRNA levels of the , angiotensin type 1 receptor gene, , and the aldosterone synthase gene, have been reported in the heart, blood vessels, and kidneys in salt-sensitive hypertension. However, the mechanism of gene regulation in each component of the RAAS in cardiovascular and renal tissues is unclear. Epigenetic mechanisms, which are important for regulating gene expression, include DNA methylation, histone post-translational modifications, and microRNA (miRNA) regulation. A close association exists between low DNA methylation at CEBP-binding sites and increased expression in visceral adipose tissue and the heart of salt-sensitive hypertensive rats. Several miRNAs influence expression and are associated with cardiovascular diseases. Expression of both and genes is regulated by DNA methylation, histone modifications, and miRNAs. Expression of both and is reversibly regulated by epigenetic modifications and is related to salt-sensitive hypertension. The mineralocorticoid receptor (MR) exists in cardiovascular and renal tissues, in which many miRNAs influence expression and contribute to the pathogenesis of hypertension. Expression of the 11beta-hydroxysteroid dehydrogenase type 2 () gene is also regulated by methylation and miRNAs. Epigenetic regulation of renal and vascular is an important pathogenetic mechanism for salt-sensitive hypertension.