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.
| 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 |
