Objective- 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. Methods and Results- 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. Conclusion- These results demonstrate that ACE2 deficiency in bone marrow-derived cells promotes atherosclerosis through regulation of Ang II/Ang-(1-7) peptides.
|Original language||English (US)|
|Number of pages||8|
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|State||Published - Apr 2011|
- angiotensin II
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine