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(Circulation Research. 2007;101:441.)
© 2007 American Heart Association, Inc.

Review

Angiotensin-Converting Enzyme and Vascular Remodeling

Sylvia Heeneman, Judith C. Sluimer, Mat J.A.P. Daemen

From the Department of Pathology, Maastricht University, Cardiovascular Research Institute Maastricht, The Netherlands.

Correspondence to Sylvia Heeneman, Maastricht University, Department of Pathology, Cardiovascular Research Institute Maastricht, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands. E-mail s.heeneman{at}path.unimaas.nl

This Review is part of a thematic series on Angiotensin-Converting Enzyme, which includes the following articles:

Six Truisms Concerning ACE and the Renin-Angiotensin System Educed From the Genetic Analysis of Mice

Angiotensin-Converting Enzyme II in the Heart and the Kidney

Signaling by the Angiotensin-Converting Enzyme

ACE Polymorphisms

Angiotensin-Converting Enzyme and Vascular Remodeling
Kathy Griendling and Rudi Busse Editors

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.

Key Words: vascular remodeling • angiotensin-converting enzyme • hypertension • atherosclerosis • restenosis