SAGE-Hindawi Access to Research Cardiology Research and Practice Volume 2011, Article ID 714515, 10 pages doi:10.4061/2011/714515 Review Article Local Bone Marrow Renin-Angiotensin System and Atherosclerosis Yavuz Beyazit,1 Tugrul Purnak,2 Gulay Sain Guven,3 and Ibrahim C. Haznedaroglu1 1 Department of Gastroenterology, Turkiye Yuksek Ihtisas Teaching and Research Hospital, 06100 Ankara, Turkey 2 Department of Gastroenterology, Ankara Numune Education and Research Hospital, 06100 Ankara, Turkey 3 Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey Correspondence should be addressed to Yavuz Beyazit, yavuzbeyaz@yahoo.com Received 28 September 2010; Revised 14 October 2010; Accepted 23 October 2010 Academic Editor: Masaki Mogi Copyright © 2011 Yavuz Beyazit et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) aﬀects the growth, production, proliferation diﬀerentiation, and function of hematopoietic cells. Angiotensin II (Ang II), the dominant eﬀector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R), has considerable proinﬂammatory and proatherogenic eﬀects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis. 1. Introduction The renin-angiotensin system (RAS) plays a crucial role in the control of blood pressure, blood ﬂow, ﬂuid volume, and electrolyte balance, and overactivity of this system contributes to the pathogenesis of a variety of clinical conditions, including onset, progression, and outcome of atherosclerosis [1–3]. Angiotensinogen (AGT) produced in the liver is the precursor of angiotensin I (Ang I), an inactive decapeptide that is converted into Ang II, the main eﬀector of the RAS. Its only role known is as a substrate for renin, a highly speciﬁc aspartyl protease. Renin that is secreted from juxtaglomerular apparatus of the kidney cleaves the N- terminal end of AGT to generate Ang I. Ang I is then activated to the Ang II by angiotensin converting enzyme (ACE), which is predominantly expressed in high concentrations on the surface of endothelial cells in the pulmonary circulation [4]. Ang II plays a main role in the RAS mediated mainly by two seven transmembrane domain receptors termed Ang II type 1 receptor (AT1R) and Ang II type 2 receptor (AT2R) showing a complex pattern of regulation and function [5]. Most of the well-known actions of Ang II-AT1R interaction causes vasoconstriction and aldosterone release from the adrenal gland. This classical description of the RAS has been expanded by recent ﬁndings that RAS is activated locally, particularly in the vessel wall, heart, the kidney, and the brain [6–14]. Ang II was also described to be produced by other enzymes such as chymase, an eﬃcient Ang II-forming serine protease [15]. It is not aﬀected by ACE inhibition and has been suggested as relevant for alternative pathways of Ang II generation [16–18]. Although several other alternative enzymes involved in Ang II formation such as tonin and cathepsins, chymase deserves special attention due to its high substrate speciﬁcity. The enzyme is also expressed in the vascular wall, where it has been suggested as a possible player in Ang II-mediated arteriosclerosis [15]. Inﬂammatory cells detected in atherosclerotic lesions are mainly originated from bone marrow (BM). The presence of a locally activated bone marrow (BM) RAS aﬀecting the growth, production, proliferation, and diﬀerentiation of hematopoietic cells was suggested in 1996 [19]. Other than a wide variety of evidences disclosed the existence of a functional local BM RAS. Angiotensin II, through interacting