CBS 2019
CBSMD教育中心
中 文

Congestive Heart Failure

Abstract

Recommended Article

Haemodynamic-guided management of heart failure (GUIDE-HF): a randomised controlled trial Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial Readmission and Mortality After Hospitalization for Myocardial Infarction and Heart Failure The Role of the Pericardium in Heart Failure: Implications for Pathophysiology and Treatment Outcomes and Effect of Treatment According to Etiology in HFrEF An Analysis of PARADIGM-HF Angiotensin–neprilysin inhibition versus enalapril in heart failure Heart Failure With Mid-Range (Borderline) Ejection Fraction: Clinical Implications and Future Directions

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.