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

Heywood, SE, Richart, AL, Henstridge, DC ORCID: 0000-0003-4988-767X, Alt, K, Kiriazis, H, Zammit, C, Carey, AL, Kammoun, HL, Delbridge, LM, Reddy, M, Chen, Y-C, Du, X-J, Hagemeyer, CE, Febbraio, MA, Siebel, AL and Kingwell, BA 2017 , 'High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice' , Science Translational Medicine, vol. 9, no. 411 , eaam6084 , doi: 10.1126/scitranslmed.aam6084.

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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.

Item Type: Article
Authors/Creators:Heywood, SE and Richart, AL and Henstridge, DC and Alt, K and Kiriazis, H and Zammit, C and Carey, AL and Kammoun, HL and Delbridge, LM and Reddy, M and Chen, Y-C and Du, X-J and Hagemeyer, CE and Febbraio, MA and Siebel, AL and Kingwell, BA
Keywords: glucose, high density lipoprotein, reconstituted high density lipoprotein, unclassified drug, glucose, high density lipoprotein, Akt signaling, animal cell, animal experiment, animal model, animal tissue, capillary density, controlled study
Journal or Publication Title: Science Translational Medicine
Publisher: American Association for the Advancement of Science
ISSN: 1946-6234
DOI / ID Number: 10.1126/scitranslmed.aam6084
Copyright Information:

Copyright 2017 The Authors

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