High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice
journal contribution
posted on 2023-05-20, 04:48authored byHeywood, 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, BA
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.
History
Publication title
Science Translational Medicine
Volume
9
Issue
411
Pagination
eaam6084
ISSN
1946-6234
Department/School
School of Health Sciences
Publisher
American Association for the Advancement of Science