Research ArticleCardiovascular Disease

High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice

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Science Translational Medicine  11 Oct 2017:
Vol. 9, Issue 411, eaam6084
DOI: 10.1126/scitranslmed.aam6084

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Lipoprotein lends a hand for heart attacks

Preventing myocyte damage after myocardial infarction could help stop the development of heart failure. Heywood et al. administered reconstituted high-density lipoprotein (rHDL) after inducing cardiac ischemia in mice and showed that treatment caused increased glucose uptake in myocytes, reduced infarct size, and improved ventricle function. rHDL was effective in prediabetic and healthy mice, suggesting that it may be a promising treatment for acute coronary syndrome.

Abstract

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.

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