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Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2075-80. doi: 10.1161/ATVBAHA.113.301777. Epub 2013 Jul 11.

Contributions of leukocyte angiotensin-converting enzyme to development of atherosclerosis.

Author information

1
Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536-0509, USA.

Abstract

OBJECTIVE:

This study determined the role of angiotensin-converting enzyme (ACE) on the development of angiotensin I-induced atherosclerosis and the contribution of leukocyte-specific expression of this enzyme.

APPROACH AND RESULTS:

To define the contribution of ACE-dependent activity to angiotensin II synthesis in atherosclerotic development, male low-density lipoprotein receptor(-/-) mice were fed a fat-enriched diet and infused with either angiotensin I or angiotensin II. The same infusion rate of these peptides had equivalent effects on atherosclerotic development. Coinfusion of an ACE inhibitor, enalapril, ablated angiotensin I-augmented atherosclerosis but had no effect on angiotensin II-induced lesion development. ACE protein was detected in several cell types in atherosclerotic lesions, with a predominance in macrophages. This cell type secreted angiotensin II, which was ablated by ACE inhibition. To study whether leukocyte ACE contributed to atherosclerosis, irradiated male low-density lipoprotein receptor(-/-) mice were repopulated with bone marrow-derived cells from either ACE(+/+) or ACE(-/-) mice and fed the fat-enriched diet for 12 weeks. Chimeric mice with ACE deficiency in bone marrow-derived cells had modestly reduced atherosclerotic lesions in aortic arches but had no effects in aortic roots.

CONCLUSIONS:

ACE mediates angiotensin I-induced atherosclerosis, and ACE expression in leukocytes modestly contributes to atherosclerotic development in hypercholesterolemic mice.

KEYWORDS:

angiotensin-converting enzyme inhibitors; angiotensins; atherosclerosis; hypercholesterolemia; macrophages; renin

PMID:
23846498
PMCID:
PMC3868562
DOI:
10.1161/ATVBAHA.113.301777
[Indexed for MEDLINE]
Free PMC Article

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