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VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.

ABSTRACT: Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain- and loss-of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor-B (VEGF-B) in the heart. A cardiomyocyte-specific VEGF-B transgene induced an expanded coronary arterial tree and reprogramming of cardiomyocyte metabolism. This was associated with protection against myocardial infarction and preservation of mitochondrial complex I function upon ischemia-reperfusion. VEGF-B increased VEGF signals via VEGF receptor-2 to activate Erk1/2, which resulted in vascular growth. Akt and mTORC1 pathways were upregulated and AMPK downregulated, readjusting cardiomyocyte metabolic pathways to favor glucose oxidation and macromolecular biosynthesis. However, contrasting with a previous theory, there was no difference in fatty acid uptake by the heart between the VEGF-B transgenic, gene-targeted or wildtype rats. Importantly, we also show that VEGF-B expression is reduced in human heart disease. Our data indicate that VEGF-B could be used to increase the coronary vasculature and to reprogram myocardial metabolism to improve cardiac function in ischemic heart disease.

SUBMITTER: Kivela R

PROVIDER: S-EPMC3958306 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.

Kivelä Riikka R Bry Maija M Robciuc Marius R MR Räsänen Markus M Taavitsainen Miia M Silvola Johanna M U JM Saraste Antti A Hulmi Juha J JJ Anisimov Andrey A Mäyränpää Mikko I MI Lindeman Jan H JH Eklund Lauri L Hellberg Sanna S Hlushchuk Ruslan R Zhuang Zhen W ZW Simons Michael M Djonov Valentin V Knuuti Juhani J Mervaala Eero E Alitalo Kari K

EMBO molecular medicine 20140121 3

Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain- and loss-of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor-B (VEGF-B) in the heart. A cardiomyocyte-specific VEGF-B transgene induced an expanded coronary arterial tree and reprogramming of cardiomyocyte metabolism. This was associated with protection against myocardial infarction and preservation of mitochondrial complex I function upon is ...[more]

PMID: 24448490

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VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.

Publications

VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.

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