Baker Heart and Diabetes Institute, Melbourne, Australia.
Department of Physiology, University of Melbourne, Melbourne, Australia.
Sci Transl Med. 2017 Oct 11;9(411). doi: 10.1126/scitranslmed.aam6084.
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.
保护急性冠状动脉综合征后的心脏是支持心脏恢复和预防心力衰竭进展的关键治疗目标。一种潜在的策略是在缺血后早期靶向心脏葡萄糖代谢，此时糖酵解对于心肌细胞存活至关重要。基于我们发现高密度脂蛋白 (HDL) 调节骨骼肌葡萄糖代谢的发现，我们现在证明，心肌缺血后单次给予重组 HDL (rHDL) 可增加心脏葡萄糖摄取，减少梗死面积，并改善小鼠的心脏重构，同时伴有功能恢复增强。这些发现同样适用于代谢正常和胰岛素抵抗的小鼠。我们进一步通过 Akt 信号通路在再灌注后 15 分钟内证实了 HDL 对心肌细胞葡萄糖摄取、糖酵解和葡萄糖氧化的直接作用。这些数据支持在原发性经皮介入治疗的情况下使用可输注的 HDL 制剂来管理急性冠状动脉综合征。
