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丙酮酸-乳酸轴调节心脏肥大和心力衰竭
作者:小柯机器人 发布时间:2020/12/17 15:00:05

美国犹他大学Stavros G. Drakos和Jared Rutter研究组合作的研究发现丙酮酸-乳酸轴调节心脏肥大和心力衰竭(HF)。该研究于2020年12月16日在线发表于国际学术期刊《细胞-代谢》。

研究人员发现线粒体丙酮酸载体(MPC)和细胞乳酸转运蛋白单羧酸盐转运蛋白4(MCT4)位于心肌细胞代谢轴中的关键节点。研究人员发现在慢性HF患者中,心脏辅助设备引起的心肌恢复与心肌MPC表达增加同时发生。

此外,在培养的心肌细胞和成年小鼠心脏中MPC的缺失足以诱导心肌肥大和HF。相反,MPC过表达以细胞自主方式减弱了药物诱导的心肌肥大。研究人员还发现了一种新型高效的MCT4抑制剂,可减缓培养心肌细胞和小鼠心肌肥大。总的来说,该研究发现丙酮酸-乳酸轴的改变是心脏肥大和心力衰竭的基本和早期特征。

据介绍,心肌细胞代谢重塑是心力衰竭的公认标志。这些代谢变化包括线粒体丙酮酸氧化减少和乳酸产生增加。

附:英文原文

Title: The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

Author: Ahmad A. Cluntun, Rachit Badolia, Sandra Lettlova, K. Mark Parnell, Thirupura S. Shankar, Nikolaos A. Diakos, Kristofor A. Olson, Iosif Taleb, Sean M. Tatum, Jordan A. Berg, Corey N. Cunningham, Tyler Van Ry, Alex J. Bott, Aspasia Thodou Krokidi, Sarah Fogarty, Sophia Skedros, Wojciech I. Swiatek, Xuejing Yu, Bai Luo, Shannon Merx, Sutip Navankasattusas, James E. Cox, Gregory S. Ducker, William L. Holland, Stephen H. McKellar, Jared Rutter, Stavros G. Drakos

Issue&Volume: 2020-12-16

Abstract: The metabolic rewiring of cardiomyocytes is a widely accepted hallmark of heart failure(HF). These metabolic changes include a decrease in mitochondrial pyruvate oxidationand an increased export of lactate. We identify the mitochondrial pyruvate carrier(MPC) and the cellular lactate exporter monocarboxylate transporter 4 (MCT4) as pivotalnodes in this metabolic axis. We observed that cardiac assist device-induced myocardialrecovery in chronic HF patients was coincident with increased myocardial expressionof the MPC. Moreover, the genetic ablation of the MPC in cultured cardiomyocytes andin adult murine hearts was sufficient to induce hypertrophy and HF. Conversely, MPCoverexpression attenuated drug-induced hypertrophy in a cell-autonomous manner. Wealso introduced a novel, highly potent MCT4 inhibitor that mitigated hypertrophy incultured cardiomyocytes and in mice. Together, we find that alteration of the pyruvate-lactateaxis is a fundamental and early feature of cardiac hypertrophy and failure.

DOI: 10.1016/j.cmet.2020.12.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30658-6

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx