Heparin inhibits intimal thickening after arterial injury. The principal objective of this proposal is to define in a rat injury model the effect of heparin on specific processes necessary for the development of intimal thickening including smooth muscle migration, proliferation, death, and connective tissue deposition. Whether heparin inhibits other forms of SMC response including normal growth and DNA endoreplication in response to hypertension will also be determined. These analyses will be compared with a similar analysis of growth inhibition using an antibody to human platelet-derived growth factor (PDGF). Since heparin may act by binding PDGF, it will be important to define the relationship between heparin and anti-PDGF antibody induced inhibition of the vascular injury response. These studies on heparin inhibition have potential clinical application since heparin-like drugs may prove useful for preventing the failure of vascular reconstructions caused by exuberant myointimal thickening. Furthermore such studies may shed light on the normal in vivo mechanisms of smooth muscle growth control. Light and electron microscopy, flow cytometry and thymidine autoradiography will be used in these experiments.
Showing the most recent 10 out of 15 publications
