Contributions of Leukocyte Angiotensin-Converting Enzyme to Development of Atherosclerosis
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.
- angiotensin-converting enzyme inhibitors
- Received November 11, 2012.
- Accepted June 27, 2013.
- © 2013 American Heart Association, Inc.