Mechanisms of ephrin-B2 signaling mediating vasodilation
Initial Award Abstract
Peripheral arterial disease (PAD) involves the narrowing of the peripheral arteries, most commonly in the pelvis and the legs. If this blockage is serious, it can cause total loss of circulation in the legs, which may require amputation. People who smoke have an increased risk for PAD. Additionally, smoking and exposure to cigarette smoke are known to impair arterial dilation, further compounding the poor circulation in the limb. |
We have generated a mutant mouse lacking a protein called ephrinB2 in the blood vessels. When surgery is performed in normal mice to block an artery to simulate PAD, we expect the blocked-blood flow to be redirected to the other connecting vessels, causing vasodilation. Our mutant mice do not show vasodilation of the connected neighboring branches of the blocked artery to the same levels that their normal littermates do; they also recover much worse from the surgery, presenting a bluish color in the paws due to the scarcity of blood flow on the early stages after surgery, and severe gangrene on the following days. These preliminary findings reveal a novel, never described role of ephrinB2 in vasodilation. The aim of this proposal is to characterize the exact role and the mechanisms regulating the function of this protein, and validate it as a possible therapeutic target to improve blood flow in the acute response to severe arterial blockage.
|Notch4 is required for tumor onset and perfusion
|Periodical: Vascular Cell
|Authors: Costa MJ, Wu X, Cuervo H, et al.