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

    Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

    Abstrakti

    "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.)"
    Alkuperäiskielienglanti
    LehtiCirculation Research
    Vuosikerta103
    Numero9
    Sivut1018-1026
    Sivumäärä9
    ISSN0009-7330
    DOI - pysyväislinkit
    TilaJulkaistu - 2008
    OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

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