The aim of this research proposal is to determine the molecular nature and polymerization capacity of fibrinogen purified from patients with non-insulin dependent diabetes mellitus (NIDDM). A comprehensive study of 100 patients with NIDDM will be undertaken and the polymerization capacity of diabetic fibrinogen categorized compared to normal. Representative samples from these categories will be analyzed for molecular composition by electrospray ionization mass spectrometry (ESI-MS). Glycation and sialylation extent will be determined and correlated to their effect on these in vitro functions: polymerization, Factor XIII cross-linking, tPA dependent activation of plasminogen, and fibrinolysis. Clot structure will be examined by permeability assays and scanning electron microscopy. In the event that fibrinogen is modified due to the progression of NIDDM, a reassessment of fibrinogen's functions within the diabetic milieu will be necessary. This assessment could lead to further understanding of fibrinogen's influence on diabetic vascular complications with the ultimate goal of developing new treatment for diabetic patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL010436-02X1
Application #
6546508
Study Section
Special Emphasis Panel (ZRG1 (02))
Program Officer
Mondoro, Traci
Project Start
2001-11-01
Project End
Budget Start
2001-11-01
Budget End
2002-10-31
Support Year
2
Fiscal Year
2002
Total Cost
$9,500
Indirect Cost
Name
Canterbury Health Ltd
Department
Type
DUNS #
City
Christchurch
State
Country
New Zealand
Zip Code
Mullin, Jennifer L; Brennan, Stephen O; Ganly, Peter S et al. (2002) Fibrinogen Hillsborough: a novel gammaGly309Asp dysfibrinogen with impaired clotting. Blood 99:3597-601