title: Contributions of leukocyte angiotensin-converting enzyme to development of atherosclerosis.
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.
  
  
  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.
authors.affiliation: Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY 40536-0509, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Lu
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.forename: Katsuya
authors.initials: K
authors.lastname: Tashiro
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Cassis
authors.forename: Alan
authors.initials: A
authors.lastname: Daugherty
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism*; D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004656:Enalapril / Q000008:administration & dosage; D006937:Hypercholesterolemia / Q000150:complications / Q000201:enzymology / Q000235:genetics; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology*; D008264:Macrophages / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D018183:Transplantation Chimera
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011973:Receptors, LDL; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin-converting enzyme inhibitors; angiotensins; atherosclerosis; hypercholesterolemia; macrophages; renin