TY - JOUR T1 - Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development JF - Genes Dev Y1 - 2010 A1 - Saharinen, Pipsa A1 - Helotera, Hanna A1 - Miettinen, Juho A1 - Norrmen, Camilla A1 - D'Amico, Gabriela A1 - Jeltsch, Michael A1 - Langenberg, Tobias A1 - Vandevelde, Wouter A1 - Ny, Annelii A1 - Dewerchin, Mieke A1 - Carmeliet, Peter A1 - Alitalo, Kari AB - The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that clp24 knockdown in Danio rerio and Xenopus laevis results in defective lymphatic development. Targeted disruption of Clp24 in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the Clp24(-/-) phenotype was further aggravated in the Vegfr2(+/LacZ) or Vegfr3(+/LacZ) backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure. VL - 24 UR - http://view.ncbi.nlm.nih.gov/pubmed/20439428 IS - 9 JO - Genes & Development ER - TY - JOUR T1 - Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium JF - Arterioscler Thromb Vasc Biol Y1 - 2008 A1 - Li, Xuri A1 - Tjwa, Marc A1 - Van Hove, Inge A1 - Enholm, Berndt A1 - Neven, Elke A1 - Paavonen, Karri A1 - Jeltsch, Michael A1 - Juan, Toni Diez A1 - Sievers, Richard E A1 - Chorianopoulos, Emmanuel A1 - Wada, Hiromichi A1 - Vanwildemeersch, Maarten A1 - Noel, Agnes A1 - Foidart, Jean-Michel A1 - Springer, Matthew L A1 - von Degenfeld, Georges A1 - Dewerchin, Mieke A1 - Blau, Helen M A1 - Alitalo, Kari A1 - Eriksson, Ulf A1 - Carmeliet, Peter A1 - Moons, Lieve AB - 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. CONCLUSIONS: VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities. VL - 28 UR - http://view.ncbi.nlm.nih.gov/pubmed/18511699 IS - 9 JO - Arteriosclerosis, Thrombosis, and Vascular Biology ER -