CBS 2019
CBSMD教育中心
中 文

血流动力学与动脉粥样硬化

Abstract

Recommended Article

Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque Phenotype in the Future: A Serial Optical Coherence Tomography and Computational Fluid Dynamics Study Coronary Microcirculation in Ischemic Heart Disease Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression Flow-Regulated Endothelial S1P Receptor-1 Signaling Sustains Vascular Development Evolving understanding of the heterogeneous natural history of individual coronary artery plaques and the role of local endothelial shear stress Low shear stress induces endothelial reactive oxygen species via the AT1R/eNOS/NO pathway
|<< 1 2 3 >>|

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.