Protecting the heart after an acute coronary syndrome is a key therapeutic goal to support cardiac recovery and prevent progression to heart failure. A potential strategy is to target cardiac glucose metabolism at the early stages after ischemia when glycolysis is critical for myocyte survival. Building on our discovery that high-density lipoprotein (HDL) modulates skeletal muscle glucose metabolism, we now demonstrate that a single dose of reconstituted HDL (rHDL) delivered after myocardial ischemia increases cardiac glucose uptake, reduces infarct size, and improves cardiac remodeling in association with enhanced functional recovery in mice. These findings applied equally to metabolically normal and insulin-resistant mice. We further establish direct effects of HDL on cardiomyocyte glucose uptake, glycolysis, and glucose oxidation via the Akt signaling pathway within 15 min of reperfusion. These data support the use of infusible HDL preparations for management of acute coronary syndromes in the setting of primary percutaneous interventions.

急性冠状动脉综合征后保护心脏是支持心脏恢复并预防心力衰竭发展的关键治疗目标。当糖酵解对于心肌细胞的生存至关重要时，一种潜在的策略是在缺血后的早期阶段针对心脏葡萄糖代谢。在我们发现高密度脂蛋白（HDL）调节骨骼肌葡萄糖代谢的基础上，我们现在证明在心肌缺血后单剂量重构的HDL（rHDL）可以增加心脏的葡萄糖摄取，减少梗塞面积并改善相关的心脏重塑具有增强的小鼠功能恢复能力。这些发现同样适用于代谢正常和胰岛素抵抗的小鼠。我们进一步建立HDL对心肌葡萄糖摄取，糖酵解，在再灌注后15分钟内通过Akt信号通路进行葡萄糖和葡萄糖氧化。这些数据支持将不溶性HDL制剂用于主要经皮介入治疗中的急性冠脉综合征的管理。