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Pulmonary Artery Denervation Using Catheter based Ultrasonic Energy Fractional Flow Reserve-Guided Complete Revascularization Improves the Prognosis in Patients With ST-Segment-Elevation Myocardial Infarction and Severe Nonculprit Disease: A DANAMI 3-PRIMULTI Substudy (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment Prognostic implications of ischemia with nonobstructive coronary arteries (INOCA): Understanding risks for improving treatment Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function Lysed Erythrocyte Membranes Promote Vascular Calcification: Possible Role of Erythrocyte-Derived Nitric Oxide A Case of Pulmonary Hypertension Associated with Idiopathic Hypereosinophilic Syndrome Increased pulmonary serotonin transporter in patients with chronic obstructive pulmonary disease who developed pulmonary hypertension The Comparison of Clinical Outcomes After Drug-Eluting Balloon and Drug-Eluting Stent Use for Left Main Bifurcation In-Stent Restenosis Prognostic Implication of Thermodilution Coronary Flow Reserve in Patients Undergoing Fractional Flow Reserve Measurement Validation of bifurcation DEFINITION criteria and comparison of stenting strategies in true left main bifurcation lesions

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.