Vascular wall ACE is not required for atherogenesis in ApoE−/− mice

• Type of Material: Article
• Authors: Daiana Weiss, Emory University; Kenneth E Bernstein, Emory University; Sebastian Fuchs, Emory University; Jonathan Adams, Emory University; Andreas Synetos, Emory University; W Robert Taylor, Emory University
• Language: English
• Date: 2010-04
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010, Elsevier
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.atherosclerosis.2009.09.069
• Title of Journal or Parent Work: Atherosclerosis
• ISSN: 0021-9150
• Volume: 209
• Issue: 2
• Start Page: 352
• End Page: 358
• Grant/Funding Information: These studies were supported by NIH grants RO1 HL70531, P01 HL58000, RO1 HL090584, K99 HL088000, R01 DK039777, R01 DK051445 and VA Merit Funding.
• Keywords: atherosclerosis; angiotensin; endothelium
• Research Categories: Health Sciences, Pathology; Health Sciences, General

Abstract

Background: It has been proposed that elements of the renin angiotensin system expressed in the arterial wall are critical for the development of atherosclerosis. Angiotensin converting enzyme (ACE) is highly expressed by the endothelium and is responsible for a critical enzymatic step in the generation of angiotensin II. However, the functional contribution of ACE expression in the vascular wall in atherogenesis is unknown. Therefore, we made use of unique genetic models in which mice without expression of ACE in the vascular wall were crossed with apoE-/- mice in order to determine the contribution of tissue ACE expression to atherosclerotic lesion formation. Methods and Results: Mice expressing either a soluble form of ACE (ACE 2/2) or mice with somatic ACE expression restricted to the liver and kidney (ACE 3/3) on an ApoE-/- background were placed on a standard chow or Western diet for 6 months. Atherosclerotic lesion area in the ACE 2/2 mice was significantly lower than that seen in the ACE 3/3 mice. However, these animals also had significantly lower blood pressure and reduced plasma ACE activity which precluded establishing a specific causal relationship between absent tissue ACE activity and decreased atherosclerotic lesion extent. Therefore, we studied the ACE 3/3 mice which are normotensive and lack vascular ACE expression. In the ACE 3/3 animals, atherosclerotic lesion area was no different from wild type controls despite reduced plasma ACE activity. Conclusions: We concluded that under these experimental conditions, expression of ACE in the arterial wall is not required for atherosclerotic lesion formation.