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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1614.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Reevaluation of the Role of VEGF-B Suggests a Restricted Role in the Revascularization of the Ischemic Myocardium

Xuri Li; Marc Tjwa; Inge Van Hove; Berndt Enholm; Elke Neven; Karri Paavonen; Michael Jeltsch; Toni Diez Juan; Richard E. Sievers; Emmanuel Chorianopoulos; Hiromichi Wada; Maarten Vanwildemeersch; Agnes Noel; Jean-Michel Foidart; Matthew L. Springer; Georges von Degenfeld; Mieke Dewerchin; Helen M. Blau; Kari Alitalo; Ulf Eriksson; Peter Carmeliet; Lieve Moons

From the Vesalius Research Center (X.L., M.T., I.V.H., E.N., T.D.J., E.C., H.W., M.D., P.C., L.M.), VIB, 3000 Leuven, Belgium; Vesalius Research Center (X.L., M.T., IV.H., E.N., T.D.J., E.C., H.W., M.D., P.C., L.M.), K.U. Leuven, 3000 Leuven, Belgium; Ludwig Institute for Cancer Research (X.L., M.V., U.E.), Karolinska Institute, Stockholm, Sweden; Molecular/Cancer Biology Laboratory (B.E., K.P., M.J., K.A.), Biomedicum Helsinki, University of Helsinki, Finland; Division of Cardiology (R.E.S., M.L.S.), University of California San Francisco; Laboratory of Biology of Tumors and Development (A.N., J.-M.F.), University of Liège, Belgium; and Baxter Laboratory in Genetic Pharmacology (M.L.S., G.v.D., H.M.B.), Stanford University, Calif. X.L. was a visiting scientist from the Ludwig Institute for Cancer Research, Stockholm, at the CTG, Leuven while performing these studies. Current address for M.T.: Leibniz AG, Center for Molecular Medicine, University of Frankfurt, Germany.

Correspondence to Peter Carmeliet, Vesalius Research Center (VRC), Flanders Institute for Biotechnology (VIB), K.U. Leuven, Campus Gasthuisberg, Herestraat 49, B-3000, Leuven, Belgium. E-mail peter.carmeliet{at}med.kuleuven.be

Objective— The endogenous role of the VEGF family member vascular endothelial growth factor-B (VEGF-B) in pathological angiogenesis remains unclear.

Methods and Results— We studied the role of VEGF-B in various models of pathological angiogenesis using mice lacking VEGF-B (VEGF-B^–/–) or overexpressing VEGF-B₁₆₇. After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B₁₆₇ overexpression enhanced revascularization of the infarct and ischemic border zone. By contrast, VEGF-B deficiency did not affect vessel growth in the wounded skin, hypoxic lung, ischemic retina, or ischemic limb. Moreover, VEGF-B₁₆₇ overexpression failed to enhance vascular growth in the skin or ischemic limb.

Conclusion— VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities.

Using loss- and gain-of-function approaches, we studied the role of VEGF-B in various models of pathological angiogenesis. VEGF-B appears to have a relatively restricted role in pathological blood vessel formation in the ischemic heart.

Key Words: VEGF-B • angiogenesis • arteriogenesis • collateral growth • cardiac ischemia • limb ischemia

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