Abstract 13928: Adropin is a Novel Regulator of Endothelial Function Through the VEGFR2- PI3K-Akt and VEGFR2- Erk1/2 Pathways
Adropin is a recently identified protein that has been implicated in the maintenance of energy homeostasis and insulin resistance. Inasmuch as vascular function and insulin sensitivity are closely related, we hypothesized that adropin may also exert direct effects on the endothelium. In vitro cell culture models were partnered with an in vivo murine injury model to determine the potential vascular effects of adropin. Adropin was expressed in human venous and coronary artery endothelial cells. Endothelial cells treated with adropin exhibited greater proliferation, migration and capillary-like tube formation and less permeability and TNF-alpha-induced apoptosis. In keeping with a vascular protective effect, adropin stimulated Akt Ser473 and eNOS Ser1177 phosphorylation. The former was abrogated in the presence of the PI3K inhibitor LY294002 while the latter was attenuated by LY294002 and by MEK1 inhibition with PD98059. Together, these findings suggest that adropin regulates NO bioavailability and events via the PI3K-Akt and ERK1/2 signaling pathways. Adropin markedly upregulated VEGFR2 transcript and protein levels and in VEGFR2-silenced endothelial cells, adropin failed to phosphorylate eNOS, Akt and ERK1/2 supporting VEGFR2 as an upstream target of adropin-mediated eNOS activation. Adropin further improved murine limb perfusion and elevated capillary density following induction of hind limb ischemia. We report a novel endothelial protective role of adropin that is mediated via upregulation of eNOS expression through the VEGFR2-PI3K-Akt and VEGFR2-ERK1/2 pathways. Adropin represents a novel target to limit diseases characterized by endothelial dysfunction in addition to its favourable metabolic profile.
- © 2010 by American Heart Association, Inc.