Abstract 11791: A Fat-Derived Factor Omentin Functions as a Modulator of Endothelial Cell Function and Ischemia-Induced Revascularization
Background: Obesity-related diseases including type 2 diabetes are associated with vascular dysfunction and impaired revascularization. Omentin is a fat-derived secretory protein, which is downregulated in association with obese complications including type 2 diabetes. However, little is known about the role of omentin in the regulation of vascular responses. Here, we examined whether omentin modulates endothelial cell function and revascularization processes in vitro and in vivo.
Methods and results: Treatment with recombinant omentin protein led to an increase in differentiation of human umbilical vein endothelium cells (HUVECs) into vascular-like structures and a decrease in apoptotic activity of HUVECs. Omentin protein also stimulated the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) in HUVECs. Inhibition of the Akt signaling cancelled the stimulatory effects of omentin on differentiation and survival of HUVECs, and reversed omentin-stimulated eNOS phosphorylation. Treatment with the NOS inhibitor also reduced the increase in HUVEC differentiation and survival caused by omentin. Systemic delivery of an adenoviral vector expressing omentin (Ad-Omentin) enhanced blood flow recovery and capillary density in ischemic limbs of wild-type mice compared with control adenoviral vector treatment. Furthermore, Ad-Omentin increased the phosphorylation of Akt and eNOS in ischemic muscles.
Conclusion: These data indicate that omentin promotes endothelial cell function and revascularization in response to tissue ischemia via activation of Akt signaling.
- © 2011 by American Heart Association, Inc.