Angiotensin-Converting Enzyme and Vascular Remodeling

• Published in: Circulation research Vol. 101; no. 5; pp. 441 - 454
• Main Authors: Heeneman, Sylvia, Sluimer, Judith C, Daemen, Mat J.A.P
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 31.08.2007; Lippincott
• Subjects: Angiotensin II - physiology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Vessels - pathology; Blood Vessels - physiopathology; Cardiology. Vascular system; Cardiovascular Diseases - physiopathology; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Fundamental and applied biological sciences. Psychology; Humans; Medical sciences; Muscle, Smooth, Vascular - pathology; Muscle, Smooth, Vascular - physiopathology; Peptidyl-Dipeptidase A - physiology; Signal Transduction - physiology; Tunica Intima - pathology; Tunica Intima - physiology; Vertebrates: cardiovascular system; Hypertension; Enzyme; atherosclerosis■restenosis; Cardiovascular disease; Vascular disease; Vascular remodeling; Restenosis; Peptidases; Vertebrata; Mammalia; Peptidyl-dipeptidase A; Atherosclerosis; Hydrolases; Peptidyl-dipeptidases; Circulatory system; angiotensin-converting enzyme
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.107.148338

Vascular remodeling is the result of a close interplay of changes in vascular tone and structure. In this review, the role of angiotension-converting enzyme (ACE) and the impact of ACE inhibition on vascular remodeling processes during vascular injury and restenosis, hypertension, atherosclerosis, and aneurysm formation are discussed. The role of ACE and angiotensin II (Ang II) in neointimal thickening has been firmly established by animal studies and is mediated by Ang II type 1 (AT1) receptor signaling events via monocyte chemoattractant protein-1 and NAD(P)H oxidase. ACE and Ang II are involved in the remodeling of large and resistance arteries during hypertension; here, cell proliferation and matrix remodeling are also regulated by signaling events downstream of the AT1 receptor. In atherosclerosis, Ang II is involved in the inflammatory and tissue response, mediated by various signaling pathways downstream of the AT1 receptor. Although ACE inhibition has been shown to inhibit atherosclerotic processes in experimental animal models, results of large clinical trials with ACE inhibitors were not conclusive. Remodeling of vessel dimensions and structure during aneurysm formation is counteracted by ACE inhibition. Here, a direct effect of ACE inhibitors on matrix metalloproteinase activity has to be considered as part of the working mechanism. The role of ACE2 in vascular remodeling has yet to be established; however, ACE2 has been shown to be associated with vascular changes in hypertension and atherosclerosis.