Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy

Terhi Kärpänen, Maija Bry, Hanna Ollila, Tuulikki Seppänen-Laakso, Erkki Liimatta, Hanna Leskinen, Riikka Kivelä, Teemu Helkamaa, Mari Merentie, Michael Jeltsch, Karri Paavonen, Leif C Andersson, Eero Mervaala, Ilmo Hassinen, Seppo Ylä-Herttuala, Matej Oresic, Kari Alitalo

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"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. (Circ Res. 2008; 103:1018-1026.)"
Original languageEnglish
JournalCirculation Research
Issue number9
Pages (from-to)1018-1026
Number of pages9
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

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