GROWTH FACTORS IN VASCULAR SMOOTH MUSCLE

Project: Research project

Description

DESCRIPTION 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.
StatusFinished
Effective start/end date8/1/977/31/02

Funding

  • National Institutes of Health: $223,264.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $223,041.00

Fingerprint

Vascular Smooth Muscle
Intercellular Signaling Peptides and Proteins
Fibroblast Growth Factor 2
Molecular Weight
Protein Isoforms
Carotid Arteries
Transforming Growth Factor beta
Aorta
Hypertension
Mesenteric Arteries
Vascular Endothelium
Wounds and Injuries
Portal Vein
Morphogenesis
Knockout Mice
Muscle Cells
Smooth Muscle Myocytes
Genes

ASJC

  • Medicine(all)