on June 29, 2006
Published online before print June 29, 2006, doi: 10.1161/01.ATV.0000234923.79173.99
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Submitted on April 7, 2006
Accepted on June 9, 2006
Fibroblast Growth Factor-2 Failed to Induce Angiogenesis in Junctional Adhesion Molecule-Deficient Mice
Vesselina G. Cooke ;
From the Department of Biological Sciences (V.G.C., M.U.N., U.P.N.), Delaware Biotechnology Institute (V.G.C., M.U.N., U.P.N.), Department of Chemistry and Biochemistry (U.P.N.), and Department of Chemical Engineering (U.P.N.), University of Delaware, Newark, DE.
* To whom correspondence should be addressed. E-mail: unaik{at}udel.edu.
Objective--We have previously shown that JAM-A regulates fibroblast growth factor-2 (FGF-2)-induced endothelial cell morphology, proliferation, and migration. Whether JAM-A is involved in FGF-2-induced angiogenesis in vivo is not known. We used JAM-A null mice to conclusively determine the role of JAM-A in FGF-2-induced neovascularization.
Methods and Results--We generated JAM-A null (JAM-A-/-) mice using gene trap technology. These mice, although viable and fertile, exhibited distorted Mendelian and sex ratios, suggesting partial embryonic lethality. Retinal fluorescein angiogram did not reveal any significant morphological differences in the vasculature of JAM-A-/- mice compared with wild-type (JAMA-A+/+) littermates. To evaluate the role of JAM-A in angiogenesis, we performed an aortic ring assay. FGF-2-induced microvessel growth was evident in aortic rings from JAM-A+/+ mice, but FGF-2 failed to induce microvessel sproutings in aortic rings from JAM-A-/- mice. In a Matrigel plug assay, a known in vivo model for angiogenesis, we found that FGF-2 induced a robust vessel growth in JAM-A+/+ mice, whereas FGF-2 failed to induce blood vessel formation in plugs from JAM-A-/- mice.
Conclusions--Our results using JAM-A-/- mice presented here conclusively establish an essential role for JAM-A in FGF-2-induced angiogenesis.
Key words: angiogenesis • aortic ring assay • bFGF • FGF-2 • integrin
v
3 •
JAM-A •
JAM-1 •
matrigel plug assay
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