Vasodilation responses to matricryptic plasma fibronectin fragments (FNp) attenuated by growth factors

Growth factors (GF) that bind to plasma fibronectin are themselves vasodilatory. Specific matricryptic plasma fibronectin fragments (FNp) that attenuate thermal burn progression in vivo are also vasodilatory in the nM range. We hypothesized that GF+FNp together would synergistically show an increased vasodilation. The cheek pouch of anesthetized (pentobarbital 70 mg/kg) hamsters (N=16) was prepared for observation of terminal arteriolar networks. Three FNp (P7, ILRWRPK; P18, YILRWRPK; P12, PSHISKYILRWRPK), and 3 GF (FGF2, basic fibroblast growth factor; VEGF, vascular endothelial cell growth factor; PDGF‐BB, platelet derived growth factor BB) were tested by micropipette application of equimolar [10‐8M] concentrations directly to the abluminal surface of the terminal arterioles. Alone, GF or FNp were vasodilatory, as expected. However, together (separate pipettes) all dilation was attenuated. Increasing FNp to 1000‐fold excess (10‐5M) alone causes constriction, however, in the presence of these GF, constriction is attenuated. Interpreting this data in terms of the clinical situation of thermal burn progression, we predict that plasma fibronectin fragments (released into the wound) initially induce vasodilation that is subsequently modulated by interaction with local growth factors. Thanks to NIH DK68401, AHA 0655908T and AFIRM.