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High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice
journal contribution
posted on 2023-05-20, 04:48 authored by Heywood, SE, Richart, AL, Darren HenstridgeDarren Henstridge, 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, Kingwell, BAProtecting 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.
History
Publication title
Science Translational MedicineVolume
9Issue
411Pagination
eaam6084ISSN
1946-6234Department/School
School of Health SciencesPublisher
American Association for the Advancement of SciencePlace of publication
United StatesRights statement
Copyright 2017 The AuthorsRepository Status
- Restricted