@article {37, title = {Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy}, journal = {Circ Res}, volume = {103}, year = {2008}, month = {2008/Oct/}, pages = {1018 - 26}, abstract = {Vascular endothelial growth factor (VEGF)-B is poorly angiogenic but prominently expressed in metabolically highly active tissues, including the heart. We produced mice expressing a cardiac-specific VEGF-B transgene via the alpha-myosin heavy chain promoter. Surprisingly, the hearts of the VEGF-B transgenic mice showed concentric cardiac hypertrophy without significant changes in heart function. The cardiac hypertrophy was attributable to an increased size of the cardiomyocytes. Blood capillary size was increased, whereas the number of blood vessels per cell nucleus remained unchanged. Despite the cardiac hypertrophy, the transgenic mice had lower heart rate and blood pressure than their littermates, and they responded similarly to angiotensin II-induced hypertension, confirming that the hypertrophy does not compromise heart function. Interestingly, the isolated transgenic hearts had less cardiomyocyte damage after ischemia. Significantly increased ceramide and decreased triglyceride levels were found in the transgenic hearts. This was associated with structural changes and eventual lysis of mitochondria, resulting in accumulation of intracellular vacuoles in cardiomyocytes and increased death of the transgenic mice, apparently because of mitochondrial lipotoxicity in the heart. These results suggest that VEGF-B regulates lipid metabolism, an unexpected function for an angiogenic growth factor.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18757827}, author = {Karpanen, Terhi and Bry, Maija and Ollila, Hanna M and Sepp{\"a}nen-Laakso, Tuulikki and Liimatta, Erkki and Leskinen, Hanna and Kivel{\"a}, Riikka and Helkamaa, Teemu and Merentie, Mari and Jeltsch, Michael and Paavonen, Karri and Andersson, Leif C and Mervaala, Eero and Hassinen, Ilmo E and Yl{\"a}-Herttuala, Seppo and Oresic, Matej and Alitalo, Kari} } @article {36, title = {Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium}, journal = {Arterioscler Thromb Vasc Biol}, volume = {28}, year = {2008}, month = {2008/Sep/}, pages = {1614 - 20}, abstract = {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.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18511699}, author = {Li, Xuri and Tjwa, Marc and Van Hove, Inge and Enholm, Berndt and Neven, Elke and Paavonen, Karri and Jeltsch, Michael and Juan, Toni Diez and Sievers, Richard E and Chorianopoulos, Emmanuel and Wada, Hiromichi and Vanwildemeersch, Maarten and Noel, Agnes and Foidart, Jean-Michel and Springer, Matthew L and von Degenfeld, Georges and Dewerchin, Mieke and Blau, Helen M and Alitalo, Kari and Eriksson, Ulf and Carmeliet, Peter and Moons, Lieve} }