Rapid confluent endothelialization decreases platelet deposition and lessens smooth muscle cell growth, minimizing thrombosis and hyperplasia after vascular interventions. VEGF121 is a soluble EC mitogen and angiogen; it will be fused to a collagen-binding domain to form a unique chimera (VEGF-CBD). Once localized to collagen, it should promote endothelialization through several mechanisms.
Aim #1 is to create VEGF-CBD, define its ability to bind to collagen type I and to exposed vessel wall collagen, and to promote in vitro EC proliferation, migration, and angiogenesis quantitatively. The hypotheses are: that VEGF-CBD will promote EC proliferation and migration in vitro without stimulating SMCs, that it will bind to collagen in vitro and to exposed vessel wall collagen in vivo prolonging bioavailability.
Aim #2 is to quantify in vivo: EC and SMC proliferation, luminal re-endothelializaton, and myointimal response to VEGF-CBD with an endothelial injury model. The hypothesis is that VEGF-CBD, delivered in vivo to the extracellular matrix, will promote confluent re-endothelialization that minimizes myointimal hyperplasia. Future promise for VEGFCBD may apply to intimal healing, surface endothelialization, and capillarization of and engineered tissues.
| Ucuzian, Areck A; Brewster, Luke P; East, Andrea T et al. (2010) Characterization of the chemotactic and mitogenic response of SMCs to PDGF-BB and FGF-2 in fibrin hydrogels. J Biomed Mater Res A 94:988-96 |
| Brewster, L P; Ucuzian, A A; Brey, E M et al. (2010) FRNK overexpression limits the depth and frequency of vascular smooth muscle cell invasion in a three-dimensional fibrin matrix. J Cell Physiol 225:562-8 |
| Brewster, Luke P; Washington, Cicely; Brey, Eric M et al. (2008) Construction and characterization of a thrombin-resistant designer FGF-based collagen binding domain angiogen. Biomaterials 29:327-36 |
| Brewster, L P; Brey, E M; Greisler, H P (2006) Cardiovascular gene delivery: The good road is awaiting. Adv Drug Deliv Rev 58:604-29 |
