Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.

Title

Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.

Creator

Dadabayev Alisher R; Yin Guotian; Latchoumycandane Calivarathan; McIntyre Thomas M; Lesnefsky Edward J; Penn Marc S

Publisher

The Journal of nutrition

Date

2014
2014-07

Description

HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.

Subject

Male; Animals; Mice; Myocardium; Lipid Metabolism; Mitochondria; Heart/drug effects; Antioxidants/administration & dosage/*metabolism/pharmacokinetics/therapeutic use; Apolipoprotein A-I/blood/genetics/*metabolism; Cardiotonic Agents/administration & dosage/metabolism/pharmacokinetics/therapeutic use; Dietary Supplements; Electron Transport Complex II/chemistry/metabolism; Electron Transport Complex III/chemistry/metabolism; Electron Transport/drug effects; Hypoalphalipoproteinemias/physiopathology; Intestinal Absorption; Myocardial Infarction/etiology/metabolism/pathology/*therapy; Myocardial Reperfusion Injury/blood/metabolism/pathology/prevention & control; Myocardium/enzymology/*metabolism/pathology; Tissue Distribution; Ubiquinone/administration & dosage/*analogs & derivatives/metabolism/pharmacokinetics/therapeutic use; Injections; Biological; Models; Animal; Knockout; Intraperitoneal; *Disease Models; Heart/drug effects/enzymology/*metabolism; Proteins; Animal Studies; Apolipoproteins; Coenzyme Q; Proteins – Metabolism; Heart – Drug Effects; Myocardial Infarction – Therapy; Apolipoproteins – Blood; Apolipoproteins – Metabolism; Antioxidants – Administration and Dosage; Antioxidants – Metabolism; Antioxidants – Pharmacokinetics; Antioxidants – Therapeutic Use; Cardiotonic Agents – Administration and Dosage; Cardiotonic Agents – Metabolism; Cardiotonic Agents – Pharmacokinetics; Cardiotonic Agents – Therapeutic Use; Coenzyme Q – Administration and Dosage; Coenzyme Q – Metabolism; Coenzyme Q – Pharmacokinetics; Coenzyme Q – Therapeutic Use; Electron Transport – Drug Effects; Inborn Errors – Physiopathology; Mitochondria – Drug Effects; Mitochondria – Metabolism; Myocardial Infarction – Etiology; Myocardial Infarction – Metabolism; Myocardial Infarction – Pathology; Myocardial Reperfusion Injury – Blood; Myocardial Reperfusion Injury – Metabolism; Myocardial Reperfusion Injury – Pathology; Myocardial Reperfusion Injury – Prevention and Control; Myocardium – Metabolism; Myocardium – Pathology

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1030–1036

Issue

7

Volume

144

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Citation

Dadabayev Alisher R; Yin Guotian; Latchoumycandane Calivarathan; McIntyre Thomas M; Lesnefsky Edward J; Penn Marc S, “Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction.,” NEOMED Bibliography Database, accessed April 16, 2021, https://neomed.omeka.net/items/show/5194.

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