Minireviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Aug 26, 2015; 6(3): 209-217
Published online Aug 26, 2015. doi: 10.4331/wjbc.v6.i3.209
Inflammation, oxidative stress and renin angiotensin system in atherosclerosis
Kazim Husain, Wilfredo Hernandez, Rais A Ansari, Leon Ferder
Kazim Husain, Leon Ferder, Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, PR 00732, United States
Wilfredo Hernandez, Department of Biochemistry, Ponce School of Medicine, Ponce, PR 00732, United States
Rais A Ansari, Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, United States
Author contributions: Husain K performed the majority of the writing, prepared the figures and tables; Hernandez W performed data accusation and writing; Ansari RA provided the input in writing the paper; Ferder L designed the outline and coordinated the writing of the paper.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kazim Husain, PhD, DABT, Professor, Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, PO Box 7004, Ponce, PR 00732, United States. khusain@psm.edu
Telephone: +1-787-8402575 Fax: +1-787-8413736
Received: January 29, 2015
Peer-review started: January 31, 2015
First decision: April 27, 2015
Revised: May 15, 2015
Accepted: June 18, 2015
Article in press: June 19, 2015
Published online: August 26, 2015
Processing time: 209 Days and 4.4 Hours
Abstract

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice.

Keywords: Atherosclerosis; Renin-angiotensin system; Inflammation; Oxidants/antioxidants imbalance; Anti-inflammatory drugs; Renin-angiotensin system blockers

Core tip: There are several reviews in the literature contributed to the pathophysiology, therapeutic options and clinical trials for atherosclerosis. However this is a first review to report the latest cellular and molecular mechanisms of the pathways of atherosclerosis including inflammation, renin-angiotensin system, oxidants/antioxidants imbalance and the efficacy of several therapeutic strategies in improving cardiovascular outcomes, and recent clinical trials reducing the progression of the pathogenesis of atherosclerosis.