Angiopoietin-2 confers Atheroprotection in apoE-/- mice by inhibiting LDL oxidation via nitric oxide

Asif Ahmed, Takeshi Fujisawa, Xi-Lin Niu, Shakil Ahmad, Bahjat Al-Ani, Kunal Chudasama, Allyah Abbas, Rahul Potluri, Vineet Bhandari, Clarence M Findley, Gregory K W Lam, Jianhua Huang, Peter W Hewett, Melissa Cudmore, Christopher D Kontos

Research output: Contribution to journalArticlepeer-review

Abstract

Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 adenovirus (AdAng-2) to apoE(-/-) mice fed a Western diet significantly reduced atherosclerotic lesion size ( approximately 40%) and oxidized LDL and macrophage content of the plaques. These beneficial effects were abolished by the inhibition of nitric oxide synthase (NOS). In endothelial cells, endothelial NOS activation per se inhibited LDL oxidation and Ang-2 stimulated NO release in a Tie2-dependent manner to decrease LDL oxidation. These findings demonstrate a novel atheroprotective role for Ang-2 when endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection.
Original languageEnglish
Pages (from-to)1333-6
Number of pages4
JournalCirculation Research
Volume104
Issue number12
DOIs
Publication statusPublished - 2009

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