This project will characterize mechanisms through which glycation of fibronectin impairs the mechanotransduction of adhesion and fluid shear stress by cultured vascular endothelial cells, as a model for events occurring in vivo in the chronic diabetic state. There is a paucity of information regarding the molecular mechanisms of endothelial dysfunction in diabetic blood vessels. Few studies to date have utilized a model of endothelium in the environment of a glycated matrix, and none have explored the regulation of such cells by fluid flow, a major determinant of endothelial function. To acheive these goals, the following Specific Aims are proposed:
Aim 1. Grow endothelial cells on glycated recombinant fibronectin and characterize the expression and function of fibronectin and integrins.
Aim 2. Determine the effects of fibronectin glycation on endothelial mechanotransduction of shear stress to MAP kinase activation and NO production.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL062885-01
Application #
2766093
Study Section
Special Emphasis Panel (ZRG2-NMS (01))
Project Start
1998-09-30
Project End
2000-08-31
Budget Start
1998-09-30
Budget End
1999-08-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kim, F; Gallis, B; Corson, M A (2001) TNF-alpha inhibits flow and insulin signaling leading to NO production in aortic endothelial cells. Am J Physiol Cell Physiol 280:C1057-65
Kim, F; Corson, M A (2000) Adhesion to fibronectin enhances MKP-1 activation in human endothelial cells. Biochem Biophys Res Commun 273:539-45