Vagus nerve stimulation optimized cardiomyocyte phenotype, sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling.
Vagus nerve stimulation optimized cardiomyocyte phenotype, sarcomere organization and energy metabolism in infarcted heart through FoxO3A-VEGF signaling.
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迷走神经刺激通过 FoxO3A-VEGF 信号优化梗死心脏中的心肌细胞表型、肌节组织和能量代谢
DOI：
10.1038/s41419-020-03142-0
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发表时间：
2020-11-12
影响因子：
9
通讯作者：
Tang JM
中科院分区：
文献类型：
--
作者：
Luo B;Wu Y;Liu SL;Li XY;Zhu HR;Zhang L;Zheng F;Liu XY;Guo LY;Wang L;Song HX;Lv YX;Cheng ZS;Chen SY;Wang JN;Tang JM
迷走神经刺激（VNS）恢复自主神经平衡，抑制炎症反应，并最大限度地减少心肌细胞损伤。然而，关于VNS在梗死心脏的心肌细胞表型、肌节组织和能量代谢中的作用知之甚少。体内VNS和体外乙酰胆碱（ACh）可优化心肌细胞α/β-MHC和α-Actinin阳性肌节的组织结构，同时减少心肌细胞F-actin的组装。因此，ACh可改善心肌细胞的葡萄糖摄取，同时减少脂质沉积，这与体内梗死心脏和体外心肌细胞中Glut 4和CPT 1 α的增加以及PDK 4的减少有关，这归因于ACh可改善VEGF-A的糖酵解和VEGF-B的脂质摄取。这导致ATP水平增加，伴随着线粒体功能的修复和氧消耗的减少。在功能上，VNS改善了左心室性能。相反，ACh-m/nAChR抑制剂或通过shRNA敲低VEGF-A/B可有力地消除VNS介导的这些作用。在机制上，ACh通过激活AKT使FoxO 3A磷酸化，从而降低心肌细胞FoxO 3A核转位水平。FoxO 3A过表达或敲低可逆转ACh对VEGF-A/B、α/β-MHC、Glut 4和CPT 1 α表达、肌节结构、葡萄糖摄取和ATP产生的特异性影响。综合来看，VNS通过激活P13 K/AKT-FoxO 3 A-VEGF-A/B信号通路，在延迟和/或阻断心肌细胞代偿性肥大向失代偿性心力衰竭转变的过程中，优化心肌细胞肌节结构和能量代谢，改善梗死心脏的心功能。
Vagus nerve stimulation (VNS) restores autonomic balance, suppresses inflammation action and minimizes cardiomyocyte injury. However, little knowledge is known about the VNS’ role in cardiomyocyte phenotype, sarcomere organization, and energy metabolism of infarcted hearts. VNS in vivo and acetylcholine (ACh) in vitro optimized the levels of α/β-MHC and α-Actinin positive sarcomere organization in cardiomyocytes while reducing F-actin assembly of cardiomyocytes. Consistently, ACh improved glucose uptake while decreasing lipid deposition in myocytes, correlating both with the increase of Glut4 and CPT1α and the decrease of PDK4 in infarcted hearts in vivo and myocytes in vitro, attributing to improvement in both glycolysis by VEGF-A and lipid uptake by VEGF-B in response to Ach. This led to increased ATP levels accompanied by the repaired mitochondrial function and the decreased oxygen consumption. Functionally, VNS improved the left ventricular performance. In contrast, ACh-m/nAChR inhibitor or knockdown of VEGF-A/B by shRNA powerfully abrogated these effects mediated by VNS. On mechanism, ACh decreased the levels of nuclear translocation of FoxO3A in myocytes due to phosphorylation of FoxO3A by activating AKT. FoxO3A overexpression or knockdown could reverse the specific effects of ACh on the expression of VEGF-A/B, α/β-MHC, Glut4, and CPT1α, sarcomere organization, glucose uptake and ATP production. Taken together, VNS optimized cardiomyocytes sarcomere organization and energy metabolism to improve heart function of the infarcted heart during the process of delaying and/or blocking the switch from compensated hypertrophy to decompensated heart failure, which were associated with activation of both P13K/AKT-FoxO3A-VEGF-A/B signaling cascade.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
11.1
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
通讯作者：
Alitalo, Kari
影响因子：
64.8
作者：
Hagberg, Carolina E.;Falkevall, Annelie;Eriksson, Ulf
通讯作者：
Eriksson, Ulf
影响因子：
18.2
作者：
Hamann, Jason J.;Ruble, Stephen B.;Sabbah, Hani N.
通讯作者：
Sabbah, Hani N.
DOI：
10.1016/s0735-1097(00)00594-5
发表时间：
2000-05-01
影响因子：
24
作者：
Hamasaki, S;Al Suwaidi, J;Lerman, A
通讯作者：
Lerman, A