The aim of this research is to develop an understanding of the chondroitin sulfate proteoglycan NG2's role in normal and pathological physiology of aortic smooth muscle cells (SMC). Vascular SMC play an integral role in the development and maintenance of the cardiovascular system; yet, little is known about the complex regulation required for their diverse functions (i.e., proliferation, migration, contractility, extracellular matrix deposition). Knowledge of the normal regulation of vascular SMC will contribute greatly to our perception of their role in vascular diseases. The proteoglycan NG2 may influence PDGF-AA stimulated biological actions in SMC. The use of SMC derived from the Spontaneously Hypertensive Rat, that express high levels of the alpha PDGF receptor, will allow indepth analyses of physical interactions between NG2 and the alpha receptor via crosslinking experiments, autophosphorylation and substrate phosphorylation by the alpha PDGF receptor. Additionally, studies will be done to quantify changes in SMC proteoglycan expression induced by growth factors and to determine any effects of other relevant molecules, such as interleukins,known to be important in pathological states. To complement the above-described studies, SMC clones not expressing NG2 will be derived from NG2-gene-knockout mice. Appropriate clones will be analyzed for differences in biological responses to growth factor stimulation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL009541-02
Application #
2459908
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1997-08-01
Project End
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037