Depletion of β3-adrenergic receptor induces left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction
Depletion of β3-adrenergic receptor induces left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction
复制标题
β3-肾上腺素能受体的耗竭通过能量代谢和心脏收缩的潜在调节诱导左心室舒张功能障碍
DOI：
10.1016/j.gene.2019.02.038
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Yuehua Fang
中科院分区：
文献类型：
--
作者：
Wenbo Yang;Xuemei Wei;Xiuxiu Su;Yan Shen;Wei Jin;Yuehua Fang
Left ventricular diastolic dysfunction (LVDD) is a central perturbation in heart failure with preserved ejection fraction, and there are currently no effective remedies to improve LVDD in clinical practice. The β3-adrenergic receptor (ADRB3) was reported to play protective effects on inhibiting myocardial fibrosis in response to hemodynamic stress. However, the effects of ADRB3 on LVDD and its underlying mechanisms are still undefined. In the current study, the role of ADRB3 in LVDD was identified in ADRB3-knockout mice. Echocardiography parameters showed that depletion of ADRB3 had little effect on cardiac systolic function but obviously led to cardiac diastolic dysfunction in vivo. Proteomics (including the global proteome, phosphorylated and acetylated proteome) and bioinformatics analysis (including GO analysis, KEGG pathway analysis, GO-Tree network, Pathway-Act network, and protein-protein interaction network) were performed on cardiac specimens of ADRB3-KO mice and wild-type mice. The results showed that the cardiac energy metabolism (especially the citrate cycle), actin cytoskeleton organization, and cardiac muscle contraction (related to mitogen-activated protein kinase, toll-like receptor, and ErbB signalling pathway) were potential core mechanisms underlying ADRB3-KO–induced LVDD. In addition, the protein-protein interaction network indicated that the core proteins associated with ADRB3-KO–induced LVDD were FGG, ALDH1A1, FGA, APOC3, SLC4A1, SERPINF2, HP, CTNNB1, and TKT. In conclusion, the absence of ADRB3 leads to LVDD, which is potentially associated with the regulation of cardiac energy metabolism, actin cytoskeleton organization, and cardiac muscle contraction.
