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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ahmed, A; Fujisawa, T; Niu, X-L; Ahmad, S; Al-Ani, B; Chudasama, K; Abbas, A; Potluri, R; Bhandari, V; Findley, CM; Lam, GKW; Huang, J; Hewett, PW; Cudmore, M; Kontos, CD

Published Date

  • June 19, 2009

Published In

Volume / Issue

  • 104 / 12

Start / End Page

  • 1333 - 1336

PubMed ID

  • 19461044

Electronic International Standard Serial Number (EISSN)

  • 1524-4571

Digital Object Identifier (DOI)

  • 10.1161/CIRCRESAHA.109.196154

Language

  • eng

Conference Location

  • United States