| 0832 Diabetic angiopathies: Experimental evidence for involvement of plasminogen activators, hyperglycemia, serum, and collagen | ||
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A.A. DECARLO, Nova Southeastern University, Ft. Lauderdale, FL, USA, and S. HALLIT, University of Alabama at Birmingham, USA Pathology brought about by prolonged hyperglycemia in diabetes involves changes to the extracellular matrix surrounding the microvasculature in retinopathy, peripheral vascular disease, and periodontitis. Angiopathy of diabetes in the periodontium is also accompanied by small vessel proliferation and branching. The plasminogen activators and their inhibitors have been shown to play a role in these changes associated with the microvasculature but there are conflicting and paradoxical reports regarding the roles of urokinase (uPA) and plasminogen activator inhibitor-1 (PAI-1). Objectives: To test the roles of uPA, PAI-1, and prolonged hyperglycemic conditions in microvessel network development and angiogenic branch formation by human dermal microvascular endothelial cells (HDMVEC). The effect of serum on angiogenic branching by HDMVEC associated with the different extracellular matrix environments was also examined. Methods: HDMVEC were either seeded upon Matrigel or were embedded within a reconstituted type I collagen matrix. Subsequent endothelial cell branching and network formation was analyzed morphologically. Results: Neutralizing polyclonal antibodies to PAI-1 and a neutralizing anti-uPA monoclonal antibody (mAb 7-18), but not a polyclonal anti-uPA antibody, significantly increased the angiogenic branching of HDMVEC relative to control conditions in both collagen and on Matrigel. Hyperglycemic conditions increased branching density of HDMVEC in collagen but did not alter the branching density of the cells on Matrigel. The effect of serum proteins on HDMVEC branching and network formation were significantly inhibitory in a concentration dependent manner when the cells were seeded on Matrigel but were significantly angiogenic in a concentration dependent manner when the cells were embedded in type I collagen. Conclusion: These data suggest a role for both uPA and PAI-1 in a wound healing scenario for the development of diabetic angiopathies triggered by exposure of microvessel endothelial cells to serum proteins and collagens of the surrounding stroma. Supported by NIH/NIDCR (R01 DE 013092-01 A1). | ||
| Seq #81 - Periodontal Medicine 11:00 AM-12:15 PM, Thursday, 7 March 2002 San Diego Convention Center Exhibit Hall C | ||
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