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Relation of Stature to Outcomes in Korean Patients Undergoing Primary Percutaneous Coronary Intervention for Acute ST-Elevation Myocardial Infarction (from the INTERSTELLAR Registry) 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3—PRIMULTI): an open-label, randomised controlled trial Aspirin-Free Prasugrel Monotherapy Following Coronary Artery Stenting in Patients With Stable CAD: The ASET Pilot Study Mechanisms of Vascular Aging, A Geroscience Perspective JACC Focus Seminar Decade-Long Trends (2001 to 2011) in the Use of Evidence-Based Medical Therapies at the Time of Hospital Discharge for Patients Surviving Acute Myocardial Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation Analysis of reperfusion time trends in patients with ST-elevation myocardial infarction across New York State from 2004 to 2012 Effect of Plaque Burden and Morphology on Myocardial Blood Flow and Fractional Flow Reserve Biological Versus Chronological Aging: JACC Focus Seminar
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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.
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