ACE inhibition counteracts vascular remodeling during aneurysm formation and impacts processes in hypertension and atherosclerosis, though clinical trial results in atherosclerosis remain inconclusive.
This review highlights the established mechanistic role of ACE and Angiotensin II in vascular remodeling across various conditions, while noting that clinical trial results for ACE inhibitors in atherosclerosis remain inconclusive.
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 (AT(1)) 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 AT(1) receptor. In atherosclerosis, Ang II is involved in the inflammatory and tissue response, mediated by various signaling pathways downstream of the AT(1) 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.
Heeneman et al. (2007) conducted a review in Vascular remodeling. ACE inhibitors was evaluated. ACE inhibition counteracts vascular remodeling during aneurysm formation and impacts processes in hypertension and atherosclerosis, though clinical trial results in atherosclerosis remain inconclusive.