Grants and Contracts Details
Description
This application requests funds for an administrative supplement to HL074219 "Integrin signalin in vascular
cells". As described in the original application, the broad goal of the research program is to understand
how integrin alphaVbeta3-dependent signaling influences vascular smooth muscle cell (SMC) growth and
migration. Abnormal vascular SMC growth and migration contributes to hypertension, atherosclerosis, and
restenosis. SMC function is controlled by complex regulatory mechanisms, which are governed in part by
interactions with the extracellular matrix. Integrins, the predominant receptors for the extracellular matrix,
activate adhesion-dependent signaling pathways, and cross-talk with growth factor and G-protein coupled
receptors to influence cellular functions. As described in a non-competing renewal, we have exciting new
data that integrin alphaVbeta3, when activated, may serve to localize the plasma enzyme autotaxin to sites
of vascular injury. Autotaxin's primary function is to generate the bioactive lipid lysophosphatidic acid (LPA),
which is a potent inducer of phenotypic modulation of SMC. In this administrative supplement, we proposed
to continue the aims of the parent grant by providing important insight into how activation of alphaVbeta3 on
SMC may promote the generation of LPA. We will test the hypothesis that recruitment of autotaxin to the
SMC surface by activated integrins increases local LPA generation, which in turn interacts with G-protein
coupled receptors to trigger SMC migration and proliferation. Most importantly, this administrative
supplement will provide a vehicle to employ a recent college graduate from the University of Kentucky and
so clearly this request will result in broad economic benefits consistent with the goals of the American
Recovery and Reinvestment Act.
Status | Finished |
---|---|
Effective start/end date | 7/15/09 → 6/30/10 |
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.