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

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.

Type Journal
ISBN 1946-6242 (Electronic) 1946-6234 (Linking)
Authors Heywood, S. E.; Richart, A. L.; Henstridge, D. C.; Alt, K.; Kiriazis, H.; Zammit, C.; Carey, A. L.; Kammoun, H. L.; Delbridge, L. M.; Reddy, M.; Chen, Y. C.; Du, X. J.; Hagemeyer, C. E.; Febbraio, M. A.; Siebel, A. L.; Kingwell, B. A.
Responsible Garvan Author Prof Mark Febbraio
Publisher Name Science Translational Medicine
Published Date 2017-10-31
Published Volume 9
Published Issue 411
Published Pages eaam6084
Status Published in-print
DOI 10.1126/scitranslmed.aam6084
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/29021167