Sistema Renina Angiotensina Y Ateroesclerosis

Hindawi Publishing Corporation Mediators of Inflammation Volume 2009, Article ID 752406, 13 pages doi:10.1155/2009/752406

Review Article The Renin-Angiotensin System Modulates Inflammatory Processes in Atherosclerosis: Evidence from Basic Research and Clinical Studies
Fabrizio Montecucco,1 Aldo Pende,2 and Francois Mach1 ¸
1 Division

of Cardiology, Foundation for Medical Researches,University Hospital of Geneva, 64 Avenue Roseraie, 1211 Geneva, Switzerland 2 Clinic of Internal Medicine I, Department of Internal Medicine, University of Genoa 16132, Genoa, Italy Correspondence should be addressed to Fabrizio Montecucco, fabrizio.montecucco@medecine.unige.ch Received 22 October 2008; Revised 7 January 2009; Accepted 29 January 2009 Recommended by Philipp M. Lepper Recent evidenceshows that the renin-angiotensin system is a crucial player in atherosclerotic processes. The regulation of arterial blood pressure was considered from its first description of the main mechanism involved. Vasoconstriction (mediated by angiotensin II) and salt and water retention (mainly due to aldosterone) were classically considered as pivotal proatherosclerotic activities. However, basic researchand animal studies strongly support angiotensin II as a proinflammatory mediator, which directly induces atherosclerotic plaque development and heart remodeling. Furthermore, angiotensin II induces proatherosclerotic cytokine and chemokine secretion and increases endothelial dysfunction. Accordingly, the pharmacological inhibition of the reninangiotensin system improves prognosis of patients withcardiovascular disease even in settings of normal baseline blood pressure. In the present review, we focused on angiotensin-convertingenzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and renin inhibitors to update the direct activities of the renin-angiotensin system in inflammatory processes governing atherosclerosis. Copyright © 2009 Fabrizio Montecucco et al. This is an open accessarticle distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Introduction
Atherosclerosis is a chronic inflammatory disease, which involves vascular cells, immune system, and several organs [1]. Although leukocytes, endothelial and smooth muscle cells have beenshown to play a crucial role in atherosclerotic inflammation, recent evidence also supports a direct activity for the liver, lung, heart, kidney, adipose tissue, adrenal, pancreatic, pituitary, and sex glands [2]. These organs produce several soluble inflammatory mediators, which orchestrate vascular and immune cell functions. Although cytokines, chemokines as well as growth factors have been shownto modulate inflammatory processes, recent studies suggest new inflammatory activities for endocrine hormones [3, 4]. The renin-angiotensin system could serve an important role in promoting inflammation [4, 5]. However, despite its first description by Tigerstedt and Bergman over a century ago [6], the role of these hormones in inflammatory processes is still unclear. The recent identification of newangiotensins and the different roles of angiotensin and renin/prorenin receptors increased the complexity of this system, suggesting that further investigations are needed to better understand the role of renin-angiotensin axis in inflammation (Figure 1) [7–9]. Furthermore, the description of the angiotensin-converting enzyme (ACE) 2 and its main product (angiotensin1–7 ) raised some controversies[10, 11]. ACE 2 and angiotensin1–7 levels are not influenced by ACE inhibitors or angiotensin II receptor blockers (ARBs). On the other hand, the “negative feed-back” regulating plasma renin activity is modulated by these drugs [12] (Figure 2). ACE 2 and angiotensin1–7 rather appear to be upregulated by these drugs maily in the myocardium and kidney [13, 14]. ACE 2 is also highly expressed in...