Involvement of the Renin‐Angiotensin System in Atherosclerosis

Abstract

The renin-angiotensin system (RAS) is a well known for its role in the regulation of the blood pressure (BP). Angiotensin II (Ang II), the main mediator of the RAS, may act either, as a systemic molecule or a locally produced factor. Within the vessel wall it has significant proinflammatory role by inducing the oxidative stress, secretion of inflammatory cytokines and adhesion molecules. Ang II could trigger proliferation of vascular smooth muscle cells (VSMC) and its migration to the outer layer of the vessel wall. It could induce the release of matrix metalloproteinase (MMPs), from human VSMC and thus increase susceptibility to rupture of atherosclerotic lesions. Binding of Ang II to AT1R/AT2R could have opposing actions in vascular injury. The ACE2/Ang (1-7)/Mas axis of the RAS also opposes the unfavourable actions of ACE/Ang II/ATR1 axis. Inhibition of RAS could reduce inflammation-associated processes in vasculature, independently of lowering BP. RAS is significantly modulated by the genes coding for this system. Certain genetic variants (SNPs) in the RAS genes have been denoted as the functional ones and have been associated with hypertension, cardiovascular phenotypes and atherosclerosis. Also, the genetic components of the RAS interfere with the regulators of gene expression by microRNAs (miRs).

Renin-Angiotensin System in Pathogenesis of Atherosclerosis and Treatment of CVD

“…Among them, there are cytokines, chemokines, growth factors, and adhesion molecules. Thus, Angiotensin II can promote atherosclerotic plaque development through upregulating VCAM-1, ICAM-1, and P-selectin in endothelial cells and, as the consequence, in circulation [9]. This contributes to the inflammatory cell adhesion to the endothelium.…”

Recent advance in treatment of atherosclerosis: Key targets and plaque-positioned delivery strategies

“…237 By renin-angiotensin pathway, generated Ang II linking to angiotensin type 1 receptor (AT1R) activates membrane-bound NADPH oxidase in ECs, SMCs, and macrophages, 227 and it also traffics to AT1R on outer mitochondria membranes, inducing mitochondria-derived ROS. 236 Importantly, NOX-derived ROS aggravates ROS overproduction by acting on eNOS and xanthine dehydrogenase. 230 …”

“…An absorbing point in Ang II is that activation of Ang II is involved in all phases of atherosclerosis, presented as stimulating TF expression, resultant endothelial dysfunction, promoting to form foam cells via regulating LOX-1 expression (SMCs) and contributory oxLDL absorption, inducing apoptosis of ECs and SMCs. 236 Thus, blocking-up in Ang II-AT1AR (Angiotensin II Type 1A Receptor) could be attainable tactics for disposing of atherosclerosis through antagonizing AT1AR or lessoning Ang II.…”

“…Growing evidence demonstrates that scavenger receptors highly express in atherosclerosis and 237 By renin-angiotensin pathway, generated Ang II linking to angiotensin type 1 receptor (AT1R) activates membrane-bound NADPH oxidase in ECs, SMCs, and macrophages, 227 and it also traffics to AT1R on outer mitochondria membranes, inducing mitochondriaderived ROS. 236 Importantly, NOX-derived ROS aggravates ROS overproduction by acting on eNOS and xanthine dehydrogenase. targeting these molecules with affinitive ligands (like decadeoxyguanine 238 and DNA oligonucleotides 239 for SRA and anti-LOX1 antibody for LOX-1) could make therapeutic drugs get to lesion site.…”

“…The mediators of NOX activity and expression are involved in excessive proatherogenic factors, such as pathological shear stress, TNFα, PDGF, oxLDL, and important angiotensin II (Ang II) 237. By renin-angiotensin pathway, generated Ang II linking to angiotensin type 1 receptor (AT1R) activates membrane-bound NADPH oxidase in ECs, SMCs, and macrophages,227 and it also traffics to AT1R on outer mitochondria membranes, inducing mitochondriaderived ROS 236. Importantly, NOX-derived ROS aggravates ROS overproduction by acting on eNOS and xanthine dehydrogenase 230.…”