Recent Faculty Publication: Renin-Angiotensin System and Cardiovascular Functions

Chia-Hua Wu, Shayan Mohammadmoradi, Jeff Z. Chen, Hisashi Sawada**, Alan Daugherty* and Hong S. Lu*

The renin-angiotensin system plays critical roles in maintaining normal cardiovascular functions and contributes to a spectrum of cardiovascular diseases. Classically, the renin-angiotensin system is composed of AGT (angiotensinogen), renin, angiotensin-converting enzyme (ACE), Ang II (angiotensin II), and 2 Ang II receptors (AT1 and AT2 receptors).1,2 AGT, a protein with 452 amino acids, is cleaved by renin to produce Ang I. Ang I is a decapeptide, which is then cleaved by ACE to produce Ang II. Ang II is an octapeptide, acting through binding to its receptors, AT1 and AT2 receptors. AT1 receptor is the major receptor for Ang II to regulate many physiological and pathophysiological functions.36 In mice, AT1 receptor has 2 subtypes, AT1a and AT1b, which have >90% sequence homology, but distinctive distributions and functions.4,712 AT1a receptor is important for blood pressure regulation and contributes to atherosclerosis and aortic aneurysms,5,13,14 whereas AT1b receptor has no evident contribution to these functions15 but is associated with vasculature contractility.16,17 AT2 receptor is abundant during fetal development but becomes low in most tissues after birth.18

In the past 2 decades, many new components in this system have been discovered. These include ACE2, a homologue of ACE, which converts Ang II to Ang(1–7) or converts Ang I to Ang(1–9).19,20 The G protein–coupled receptor Mas1 was identified as the receptor of Ang(1–7).21

This review highlights some recent publications in ATVB that have provided insights into understanding the classic components of the renin-angiotensin system and its alternative components contributing to cardiovascular functions. We will focus on effects of this hormonal system on cardiac dysfunction, hypertension, atherosclerosis, and aortic aneurysms.2229

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*Saha Cardiovascular Research Center Faculty

**Saha Cardiovascular Research Cneter Fellow