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

Sarah E. Heywood, Adele L. Richart, Darren C. Henstridge, Karen Alt, Helen Kiriazis, Claire Zammit, Andrew L. Carey, Helene L. Kammoun, Lea M. Delbridge, Medini Reddy, Yi Ching Chen, Xiao Jun Du, Christoph E. Hagemeyer, Mark A. Febbraio, Andrew L. Siebel, Bronwyn A. Kingwell

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Article numbereaam6084
Number of pages10
JournalScience Translational Medicine
Volume9
Issue number411
DOIs
Publication statusPublished - 11 Oct 2017

Cite this

@article{402a8ce36c034f3b94ab0b8dd53e142e,
title = "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.",
author = "Heywood, {Sarah E.} and Richart, {Adele L.} and Henstridge, {Darren C.} and Karen Alt and Helen Kiriazis and Claire Zammit and Carey, {Andrew L.} and Kammoun, {Helene L.} and Delbridge, {Lea M.} and Medini Reddy and Chen, {Yi Ching} and Du, {Xiao Jun} and Hagemeyer, {Christoph E.} and Febbraio, {Mark A.} and Siebel, {Andrew L.} and Kingwell, {Bronwyn A.}",
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day = "11",
doi = "10.1126/scitranslmed.aam6084",
language = "English",
volume = "9",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
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High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice. / Heywood, Sarah E.; Richart, Adele L.; Henstridge, Darren C.; Alt, Karen; Kiriazis, Helen; Zammit, Claire; Carey, Andrew L.; Kammoun, Helene L.; Delbridge, Lea M.; Reddy, Medini; Chen, Yi Ching; Du, Xiao Jun; Hagemeyer, Christoph E.; Febbraio, Mark A.; Siebel, Andrew L.; Kingwell, Bronwyn A.

In: Science Translational Medicine, Vol. 9, No. 411, eaam6084, 11.10.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - High-density lipoprotein delivered after myocardial infarction increases cardiac glucose uptake and function in mice

AU - Heywood, Sarah E.

AU - Richart, Adele L.

AU - Henstridge, Darren C.

AU - Alt, Karen

AU - Kiriazis, Helen

AU - Zammit, Claire

AU - Carey, Andrew L.

AU - Kammoun, Helene L.

AU - Delbridge, Lea M.

AU - Reddy, Medini

AU - Chen, Yi Ching

AU - Du, Xiao Jun

AU - Hagemeyer, Christoph E.

AU - Febbraio, Mark A.

AU - Siebel, Andrew L.

AU - Kingwell, Bronwyn A.

PY - 2017/10/11

Y1 - 2017/10/11

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AB - 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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