Multiple roles of angiopoietins in atherogenesis

The roles of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) during vascular development have been extensively investigated, as has been their role in controlling the responsiveness of the endothelium to exogenous cytokines. However, very little is known about the role of these vascular morphogenic molecules in the pathogenesis of atherosclerosis. Here, we summarize the recent research into angiopoietins in atherosclerosis.

Angiopoietin-2 is a context-dependent agonist that protects against the development of arteriosclerosis in rat cardiac allograft. A recent study showed, contrary to expectations, that a single systemic administration of adenoviral Ang-2 to apoE mice, fed a Western diet, reduced atherosclerotic lesion size and LDL oxidation in a nitric oxide synthase dependent manner. In contrast, overexpression of Ang-1 fails to protect from rat cardiac allograft due to smooth muscle cell activation. The potential proatherogenic effect of Ang-1 is further supported by the induction of chemotaxis of monocytes by Ang-1 in a manner that is independent of Tie-2 and integrin binding. These studies highlight the need for extensive research to better understand the role of angiopoietins in the cardiovascular setting.

Ang-2 inhibits atherosclerosis by limiting LDL oxidation via stimulation of nitric oxide production. In contrast, Ang-1 can promote monocyte and neutrophil migration. The angiopoietin-Tie-2 system provides an important new target for modulating vascular function.