Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium

被引:98
作者
Li, Xuri [1 ,2 ]
Tjwa, Marc [1 ]
Van Hove, Inge [1 ]
Enholm, Berndt [3 ]
Neven, Elke [1 ]
Paavonen, Karri [3 ]
Jeltsch, Michael [3 ]
Juan, Toni Diez [1 ]
Sievers, Richard E. [4 ]
Chorianopoulos, Emmanuel [1 ]
Wada, Hiromichi [1 ]
Vanwildemeersch, Maarten [2 ]
Noel, Agnes [5 ]
Foidart, Jean-Michel [5 ]
Springer, Matthew L. [4 ,6 ]
von Degenfeld, Georges [6 ]
Dewerchin, Mieke [1 ]
Blau, Helen M. [6 ]
Alitalo, Kari [3 ]
Eriksson, Ulf [2 ]
Carmeliet, Peter [1 ]
Moons, Lieve [1 ]
机构
[1] Katholieke Univ Leuven VIB, VRC, B-3000 Louvain, Belgium
[2] Karolinska Inst, Ludwig Inst Canc Res, Stockholm, Sweden
[3] Univ Helsinki, Biomedicum Helsinki, Lab Mol Canc Biol, FIN-00014 Helsinki, Finland
[4] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA
[5] Univ Liege, Lab Biol Tumors & Dev, B-4000 Liege, Belgium
[6] Stanford Univ, Baxter Lab Genet Pharmacol, Stanford, CA 94305 USA
基金
瑞典研究理事会;
关键词
VEGF-B; angiogenesis; arteriogenesis; collateral growth; cardiac ischemia; limb ischemia;
D O I
10.1161/ATVBAHA.107.158725
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-B-167. After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B-167 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-B-167 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.
引用
收藏
页码:1614 / 1620
页数:7
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