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Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: the Nordic bifurcation study Optical Coherence Tomography Predictors for Recurrent Restenosis After Paclitaxel-Coated Balloon Angioplasty for Drug-Eluting Stent Restenosis The European bifurcation club Left Main Coronary Stent study: a randomized comparison of stepwise provisional vs. systematic dual stenting strategies (EBC MAIN) Comparison of the safety and efficacy of two types of drug-eluting balloons (RESTORE DEB and SeQuent® Please) in the treatment of coronary in-stent restenosis: study protocol for a randomized controlled trial (RESTORE ISR China) Multicentre, randomized comparison of two-stent and provisional stenting techniques in patients with complex coronary bifurcation lesions: the DEFINITION II trial Comparison of new-generation drug-eluting stents versus drug-coated balloon for in-stent restenosis: a meta-analysis of randomised controlled trials Sustainable Antirestenosis Effect With a Low-Dose Drug-Coated Balloon: The ILLUMENATE European Randomized Clinical Trial 2-Year Results In-Hospital Outcomes of Chronic Total Occlusion Percutaneous Coronary Interventions in Patients With Prior Coronary Artery Bypass Graft Surgery Long-term clinical outcomes after treatment of stent restenosis with two drug-coated balloons Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial
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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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