| Endothelial cell responses to injury are important
in normal wound healing and in pathologic conditions including
atherosclerosis. We are investigating how these responses are
controlled with a focus on fibroblast growth factors and vascular
endothelial growth factor. Recent findings in our laboratory
have shown that FGF-2 and VEGF bind with high affinity to fibrinogen
and fibrin and that fibrinogen potentiates the proliferative
capacity of FGF-2. The association with fibrin(ogen) is particularly
important since fibrin forms the temporary matrix needed for
wound healing and also plays a role in regulation of endothelial
cell function. Ongoing studies will identify the binding sites
involved in this interaction and further investigate the functional
importance of FGF and VEGF binding to fibrin(ogen), examining
implications for endothelial cell protein secretion, migration
and angiogenesis.
A second project concerns the effect of ultrasound on fibrinolysis,
the enzymatic process of blood clot dissolution. We have demonstrated
that low intensity ultrasound accelerates fibrinolysis by
non-thermal mechanisms. Ongoing studies will examine the biochemical
and physical basis of this effect. Using in vitro and animal
models, we will also determine the optimum conditions for
the clinical application of ultrasound to enhance fibrinolytic
therapy for treatment of cerebral, coronary and peripheral vascular
thrombosis.
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Ryan DH, Crowther M, Ginsberg J, Francis CW. Relationship
of factor V Leiden genotype to risk of acute deep vein thrombosis
following joint replacement surgery. Ann Int Med 128:270-276,
1998.
Suchkove VN, Baggs RB, Francis CW. Effect of 40-kHz ultrasound on acute thromotic ischemia in a rabbit femoral artery thrombosis model. Circ 101:2296-2301, 2000.
Sahni A, Sporn LA, Francis CW. Potentiation of endothelial cell proliferation by figrin(ogen)-bound fibroblast growth factor-2. J Biol Chem 274:14396-14941, 1999.
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