Contributions of leukocyte angiotensin-converting enzyme to development of atherosclerosis

Xiaofeng Chen, Hong Lu, Mingming Zhao, Katsuya Tashiro, Lisa A. Cassis, Alan Daugherty

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


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.

Original languageEnglish
Pages (from-to)2075-2080
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number9
StatePublished - Sep 2013


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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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