CBS 2019
CBSMD教育中心
English

科学研究

科研文章

荐读文献

The year in cardiovascular medicine 2020: acute coronary syndromes and intensive cardiac care 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non–ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures Clinical and genetic characteristics of pulmonary arterial hypertension in Lebanon Left Main Stenting: What We Have Learnt So Far? Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial Cardiac Troponin Composition Characterization after Non ST-Elevation Myocardial Infarction: Relation with Culprit Artery, Ischemic Time Window, and Severity of Injury Myocardial Inflammation Predicts Remodeling and Neuroinflammation After Myocardial Infarction Uptake of Drug-Eluting Bioresorbable Vascular Scaffolds in Clinical Practice : An NCDR Registry to Practice Project Comparison in prevalence, predictors, and clinical outcome of VSR versus FWR after acute myocardial infarction: The prospective, multicenter registry MOODY trial-heart rupture analysis Healed Culprit Plaques in Patients With Acute Coronary Syndromes

Original Research2020 Dec 11;S1550-4131(20)30658-6.

JOURNAL:Cell Metab. Article Link

The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure

AA Cluntun, R Badolia, SG Drakos et al. Keywords: LVAD; MCT4; MPC; VB124; cardiac metabolism; heart failure; hypertrophy; lactate; mitochondria; pyruvate

ABSTRACT

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