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Updated: Oct 4, 2026
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Targeting the ENO1 metabolic checkpoint via microenvironment-responsive nanotherapeutics promotes postinfarction
Ruoshui Li1,2,3,4, Gaoyang Li1,2,3, Jie Li3,5,6
1Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Abstract:
Myocardial infarction (MI) triggers persistent inflammatory dysregulation, wherein macrophages undergo glycolytic reprogramming and adopt an inflammatory phenotype that impairs cardiac repair. However, the specific metabolic drivers underlying post-MI macrophage dysfunction remain unclear. Here, we identify enolase 1 (ENO1)-a glycolytic enzyme up-regulated in post-MI macrophages-as a critical regulator of macrophage metabolic fate and inflammatory function. To intervene, we engineered an acid-responsive nanocarrier (PECS) that externalizes phosphatidylserine within the acidic infarct microenvironment, facilitating selective macrophage uptake. Intracellular delivery of siENO1 suppressed glycolytic flux, thereby curbing lactate accumulation and relieving its metabolic inhibition of KLF4, which initiated anti-inflammatory reprogramming. In vivo, PECS-loaded siENO1 (siENO1@PECS) treatment attenuated infarct size, fibrosis, and cardiomyocyte apoptosis while improving ventricular function. Collectively, these findings identify ENO1 as a critical metabolic checkpoint in post-MI macrophage regulation and demonstrate a bioresponsive nanocarrier strategy for precise gene modulation to enhance cardiac repair.
