The overall goal is to use genetically-altered mice to determine the roles of FGF2 and TGFbeta1 in the morphogenesis and contractile function of vascular smooth muscle cells in major vessels, including aorta, carotid artery, portal vein, and mesenteric resistance artery, as well as in the response of aorta and carotid artery VSM to hypertension and arterial injury. Morphogenetic and physiological analyses and microsurgical procedures for inducing hypertension and arterial injury will be applied to these mutant mice. Since mouse FGF2 has one low molecular weight (lmw) and two high molecular weight (hmw) isoforms that are thought to have different functions, mouse strains deficient in either the lmw or hmw isoforms will be made to determine functional specificity of the isoforms in developing normal, diseased and injured VSM. To determine whether the expected VSM defects of the TGFB knockout mouse are cell autonomous, due to paracrine activity of vascular endothelium, or secondary to inflammatory disorders of the TGFbeta-deficient mouse, the PI will generate conditional TGFbeta knockout strains in which the TGFB1 function is ablated only in muscle cells using the SM22 promoter in conjunction with a cre/recombinase targeting system. Additional studies will also investigate the interplay between FGF2 and TGFB1 in a mouse strain with genetically combined ablations of both genes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058511-02
Application #
2750622
Study Section
Pathology A Study Section (PTHA)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Genetics
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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