Angiotensin-converting enzyme 2 deficiency in whole body or bone marrow-derived cells increases atherosclerosis in low-density lipoprotein receptor-/- mice.

Published

Journal Article

The renin-angiotensin system contributes to atherosclerotic lesion formation. Angiotensin-converting enzyme 2 (ACE2) catabolizes angiotensin II (Ang II) to angiotensin 1-7 (Ang-(1-7)) to limit effects of the renin-angiotensin system. The purpose of this study was to define the role of ACE2 in atherosclerosis.Male Ace2(-/y) mice in an low-density lipoprotein receptor-deficient background were fed a high-fat diet for 3 months. ACE2 deficiency increased atherosclerotic area (Ace2(+/y), 17 ± 1; Ace2(-/y), 23 ± 2 mm(2), P < 0.002). This increase was blunted by losartan. To determine whether leukocytic ACE2 influenced atherosclerosis, irradiated low-density lipoprotein receptor-deficient male mice were repopulated with bone marrow-derived cells from Ace2(+/y) or Ace2(-/y) mice and fed a high-fat diet for 3 months. ACE2 deficiency in bone marrow-derived cells increased atherosclerotic area (Ace2(+/y), 1.6 ± 0.3; Ace2(-/y), 2.8 ± 0.3 mm(2); P < 0.05). Macrophages from Ace2(-/y) mice exhibited increased Ang II secretion and elevated expression of inflammatory cytokines. Conditioned media from mouse peritoneal macrophages of Ace2(-/y) mice increased monocyte adhesion to human umbilical vein endothelial cells. Incubation of human umbilical vein endothelial cells with Ang II promoted monocyte adhesion, which was blocked by Ang-(1-7). Coinfusion of Ang-(1-7) with Ang II reduced atherosclerosis.These results demonstrate that ACE2 deficiency in bone marrow-derived cells promotes atherosclerosis through regulation of Ang II/Ang-(1-7) peptides.

Full Text

Cited Authors

  • Thatcher, SE; Zhang, X; Howatt, DA; Lu, H; Gurley, SB; Daugherty, A; Cassis, LA

Published Date

  • April 2011

Published In

Volume / Issue

  • 31 / 4

Start / End Page

  • 758 - 765

PubMed ID

  • 21252069

Pubmed Central ID

  • 21252069

Electronic International Standard Serial Number (EISSN)

  • 1524-4636

International Standard Serial Number (ISSN)

  • 1079-5642

Digital Object Identifier (DOI)

  • 10.1161/ATVBAHA.110.221614

Language

  • eng