Kivelae 2014 EMBO Mol Med
|Kivelä R, Bry M, Robciuc MR, Räsänen M, Taavitsainen M, Silvola JM, Saraste A, Hulmi JJ, Anisimov A, Mäyränpää MI, Lindeman JH, Eklund L, Hellberg S, Hlushchuk R, Zhuang ZW, Simons M, Djonov V, Knuuti J, Mervaala E, Alitalo K (2016) VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart. EMBO Mol Med 6:307-21.|
Kivelae R, Bry M, Robciuc MR, Raesaenen M, Taavitsainen M, Silvola JM, Saraste A, Hulmi JJ, Anisimov A, Maeyraenpaeae MI, Lindeman JH, Eklund L, Hellberg S, Hlushchuk R, Zhuang ZW, Simons M, Djonov V, Knuuti J, Mervaala E, Alitalo K (2014) EMBO Mol Med
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.
• Keywords: Angiogenesis, Endothelial cell, Ischemia, Metabolism, VEGF-B
• O2k-Network Lab: FI Helsinki Mervaala E
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Cardiovascular Stress:Ischemia-reperfusion Organism: Rat Tissue;cell: Heart Preparation: Homogenate
Coupling state: LEAK, OXPHOS, ET Pathway: F, N, S, NS HRR: Oxygraph-2k