Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin-2 (Ang-2), a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of adenoviral Ang-2 (AdAng-2) to apoE-/- mice fed a Western diet significantly reduced atherosclerotic lesion size (~40%) and oxidized LDL and macrophage content of the plaques. Nitric oxide (NO) synthase (NOS) inhibitor abolished these beneficial effects of Ang-2. In endothelial cells, eNOS 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 where endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection.
Keywords: Angiopoietin-2, Atherosclerosis, Endothelial cells, LDL cholesterol, Nitric oxide, Nitric oxide synthases