VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart.
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DOI：
10.1002/emmm.201303147
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发表时间：
2014-03
影响因子：
11.1
通讯作者：
Alitalo, Kari
中科院分区：
文献类型：
--
作者：
Kivela, Riikka;Bry, Maija;Robciuc, Marius R.;Rasanen, Markus;Taavitsainen, Miia;Silvola, Johanna M. U.;Saraste, Antti;Hulmi, Juha J.;Anisimov, Andrey;Mayranpaa, Mikko I.;Lindeman, Jan H.;Eklund, Lauri;Hellberg, Sanna;Hlushchuk, Ruslan;Zhuang, Zhen W.;Simons, Michael;Djonov, Valentin;Knuuti, Juhani;Mervaala, Eero;Alitalo, Kari
血管生成生长因子最近已与组织代谢有关。我们已经使用遗传获得和功能丧失模型来阐明血管内皮生长因子-B（VEGF-B）在心脏中的作用和机制。心肌细胞特异性VEGF-B转基因诱导扩张的冠状动脉树和心肌细胞代谢的重编程这与缺血再灌注时心肌梗死的保护和线粒体复合物I功能的保护有关。VEGF-B通过VEGF受体-2增加VEGF信号以激活Erk 1/2，这导致血管生长。Akt和mTORC 1途径上调，AMPK下调，重新调整心肌细胞代谢途径，有利于葡萄糖氧化和大分子生物合成。然而，与先前的理论相比，VEGF-B转基因、基因靶向或野生型大鼠之间的心脏脂肪酸摄取没有差异。重要的是，我们还表明，VEGF-B表达在人类心脏病中减少。我们的数据表明，VEGF-B可用于增加冠状动脉血管和重新编程心肌代谢，以改善缺血性心脏病的心功能。心血管系统;代谢参见：C Kupatt和R Hinkel（2014年3月）
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. Subject Categories Cardiovascular System; Metabolism See also: C Kupatt and R Hinkel (March 2014)
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影响因子：
12.4
作者：
Huusko, Jenni;Lottonen, Line;Yla-Herttuala, Seppo
通讯作者：
Yla-Herttuala, Seppo
用于定量小鼠心脏体内缺血再灌注损伤的精制方法。
DOI：
10.1152/ajpheart.00836.2009
发表时间：
2009-12
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Bohl S;Medway DJ;Schulz-Menger J;Schneider JE;Neubauer S;Lygate CA
通讯作者：
Lygate CA
影响因子：
13.6
作者：
Doroudgar S;Glembotski CC
通讯作者：
Glembotski CC
影响因子：
20.1
作者：
Accornero, Federica;van Berlo, Jop H.;Molkentin, Jeffery D.
通讯作者：
Molkentin, Jeffery D.
影响因子：
5.6
作者：
Kemi, Ole Johan;Ceci, Marcello;Ellingsen, Oyvind
通讯作者：
Ellingsen, Oyvind