CBS 2019
CBSMD教育中心
中 文

充血性心力衰竭

Abstract

Recommended Article

The pyruvate-lactate axis modulates cardiac hypertrophy and heart failure The Hospital Readmissions Reduction Program Nationwide Perspectives and Recommendations: A JACC: Heart Failure Position Paper A randomized controlled trial to evaluate the safety and efficacy of cardiac contractility modulation in patients with systolic heart failure: rationale, design, and baseline patient characteristics. A Fully Magnetically Levitated Left Ventricular Assist Device — Final Report Effects of Dapagliflozin on Symptoms, Function and Quality of Life in Patients with Heart Failure and Reduced Ejection Fraction: Results from the DAPA-HF Trial Impact of Myocardial Scar on Prognostic Implication of Secondary Mitral Regurgitation in Heart Failure In acute HF and iron deficiency, IV ferric carboxymaltose reduced HF hospitalizations, but not CV death, at 1 y A Fully Magnetically Levitated Circulatory Pump for Advanced Heart Failure

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.