Genetic Ace2 Deficiency Accentuates Vascular Inflammation and Atherosclerosis in the ApoE Knockout Mouse
- 1 October 2010
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 107 (7), 888-897
- https://doi.org/10.1161/circresaha.110.219279
Abstract
Rationale:Angiotensin-converting enzyme (ACE)2 opposes the actions of angiotensin (Ang) II by degrading it to Ang 1-7. Objective:Given the important role of Ang II/Ang 1-7 in atherogenesis, we investigated the impact of ACE2 deficiency on the development of atherosclerosis. Methods and Results:C57Bl6, Ace2 knockout (KO), apolipoprotein E (ApoE) KO and ApoE/Ace2 double KO mice were followed until 30 weeks of age. Plaque accumulation was increased in ApoE/Ace2 double KO mice when compared to ApoE KO mice. This was associated with increased expression of adhesion molecules and inflammatory cytokines, including interleukin-6, monocyte chemoattractant protein-1, and vascular cell adhesion molecule-1, and an early increase in white cell adhesion across the whole aortae on dynamic flow assay. In the absence of a proatherosclerotic (ApoE KO) genotype, ACE2 deficiency was also associated with increased expression of these markers, suggesting that these differences were not an epiphenomenon. ACE inhibition prevente...This publication has 34 references indexed in Scilit:
- Vasoprotective and Atheroprotective Effects of Angiotensin (1-7) in Apolipoprotein E–Deficient MiceArteriosclerosis, Thrombosis, and Vascular Biology, 2010
- Progression of Cardiovascular Damage: The Role of Renin–Angiotensin System BlockadeThe American Journal of Cardiology, 2010
- Inflammation in Atherosclerosis From Pathophysiology to PracticeJournal of the American College of Cardiology, 2009
- A Role of Matrix Metalloproteinase-8 in AtherosclerosisCirculation Research, 2009
- Role of the T cell in the genesis of angiotensin II–induced hypertension and vascular dysfunctionThe Journal of Experimental Medicine, 2007
- Altered blood pressure responses and normal cardiac phenotype in ACE2-null miceJCI Insight, 2006
- Role of the Renin-Angiotensin-Aldosterone System and Proinflammatory Mediators in Cardiovascular DiseaseThe American Journal of Cardiology, 2006
- Inflammation, Atherosclerosis, and Coronary Artery DiseaseThe New England Journal of Medicine, 2005
- A Human Homolog of Angiotensin-converting EnzymeJournal of Biological Chemistry, 2000
- Enhanced atherosclerosis and kidney dysfunction in eNOS–/–Apoe–/– mice are ameliorated by enalapril treatmentJCI Insight, 2000