Overexpression of Vascular Endothelial Growth Factor-B in Mouse Heart Alters Cardiac Lipid Metabolism and Induces Myocardial Hypertrophy

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

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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 α-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.
Original languageEnglish
Pages (from-to)1018-1026
Number of pages9
JournalCirculation Research
Volume103
Issue number9
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

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Keywords

  • VEGF-B
  • cardiac hypertrophy
  • cardiac metabolism
  • fatty acids
  • mitochondria

Cite this

Karpanen, T., Bry, M., Ollila, H. M., Seppänen-Laakso, T., Liimatta, E., Leskinen, H., Kivelä, R., Helkamaa, T., Merentie, M., Jeltsch, M., Paavonen, K., Andersson, L. C., Mervaala, E., Hassinen, I. E., 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, 103(9), 1018-1026. https://doi.org/10.1161/CIRCRESAHA.108.178459