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

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    "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.)"
    Originalspråkengelska
    TidskriftCirculation Research
    Volym103
    Utgåva9
    Sidor (från-till)1018-1026
    Antal sidor9
    ISSN0009-7330
    DOI
    StatusPublicerad - 2008
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Kärpänen, Terhi ; Bry, Maija ; Ollila, Hanna ; Seppänen-Laakso, Tuulikki ; Liimatta, Erkki ; Leskinen, Hanna ; Kivelä, Riikka ; Helkamaa, Teemu ; Merentie, Mari ; Jeltsch, Michael ; Paavonen, Karri ; Andersson, Leif C ; Mervaala, Eero ; Hassinen, Ilmo ; Ylä-Herttuala, Seppo ; Oresic, Matej ; Alitalo, Kari. / Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy. I: Circulation Research. 2008 ; Vol. 103, Nr. 9. s. 1018-1026.
    @article{975d846aa616468aad7b65c4118e78d6,
    title = "Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy",
    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. (Circ Res. 2008; 103:1018-1026.){"}",
    author = "Terhi K{\"a}rp{\"a}nen and Maija Bry and Hanna Ollila and Tuulikki Sepp{\"a}nen-Laakso and Erkki Liimatta and Hanna Leskinen and Riikka Kivel{\"a} and Teemu Helkamaa and Mari Merentie and Michael Jeltsch and Karri Paavonen and Andersson, {Leif C} and Eero Mervaala and Ilmo Hassinen and Seppo Yl{\"a}-Herttuala and Matej Oresic and Kari Alitalo",
    year = "2008",
    doi = "10.1161/CIRCRESAHA.108.178459",
    language = "English",
    volume = "103",
    pages = "1018--1026",
    journal = "Circulation Research",
    issn = "0009-7330",
    publisher = "Lippincott williams & wilkins",
    number = "9",

    }

    Kärpänen, T, Bry, M, Ollila, H, Seppänen-Laakso, T, Liimatta, E, Leskinen, H, Kivelä, R, Helkamaa, T, Merentie, M, Jeltsch, M, Paavonen, K, Andersson, LC, Mervaala, E, Hassinen, I, Ylä-Herttuala, S, Oresic, M & Alitalo, K 2008, 'Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy', Circulation Research, vol. 103, nr. 9, s. 1018-1026. https://doi.org/10.1161/CIRCRESAHA.108.178459

    Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy. / Kärpänen, Terhi; Bry, Maija; Ollila, Hanna; Seppänen-Laakso, Tuulikki; Liimatta, Erkki; Leskinen, Hanna; Kivelä, Riikka; Helkamaa, Teemu; Merentie, Mari; Jeltsch, Michael; Paavonen, Karri; Andersson, Leif C; Mervaala, Eero; Hassinen, Ilmo; Ylä-Herttuala, Seppo; Oresic, Matej; Alitalo, Kari.

    I: Circulation Research, Vol. 103, Nr. 9, 2008, s. 1018-1026.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - Overexpression of vascular endothelial growth factor-B in mouse heart alters cardiac lipid metabolism and induces myocardial hypertrophy

    AU - Kärpänen, Terhi

    AU - Bry, Maija

    AU - Ollila, Hanna

    AU - Seppänen-Laakso, Tuulikki

    AU - Liimatta, Erkki

    AU - Leskinen, Hanna

    AU - Kivelä, Riikka

    AU - Helkamaa, Teemu

    AU - Merentie, Mari

    AU - Jeltsch, Michael

    AU - Paavonen, Karri

    AU - Andersson, Leif C

    AU - Mervaala, Eero

    AU - Hassinen, Ilmo

    AU - Ylä-Herttuala, Seppo

    AU - Oresic, Matej

    AU - Alitalo, Kari

    PY - 2008

    Y1 - 2008

    N2 - "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.)"

    AB - "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.)"

    U2 - 10.1161/CIRCRESAHA.108.178459

    DO - 10.1161/CIRCRESAHA.108.178459

    M3 - Article

    VL - 103

    SP - 1018

    EP - 1026

    JO - Circulation Research

    JF - Circulation Research

    SN - 0009-7330

    IS - 9

    ER -