Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor NG-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production.
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Research Article|
July 03 2015
Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction
Mi Zhou;
Mi Zhou
*Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Clinical Center for Diabetes, Shanghai, China
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Yuqian Bao;
Yuqian Bao
*Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Clinical Center for Diabetes, Shanghai, China
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Haobo Li;
Haobo Li
†Department of Anesthesiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Yong Pan;
Yong Pan
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
§Department of Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Lingling Shu;
Lingling Shu
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
§Department of Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Zhengyuan Xia;
Zhengyuan Xia
†Department of Anesthesiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
¶Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Donghai Wu;
Donghai Wu
║Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
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Karen S.L. Lam;
Karen S.L. Lam
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
§Department of Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
¶Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Paul M. Vanhoutte;
Paul M. Vanhoutte
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
¶Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
**Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Aimin Xu;
Aimin Xu
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
§Department of Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
¶Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
**Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
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Weiping Jia;
*Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital; Shanghai Diabetes Institute; Shanghai Key Laboratory of Diabetes Mellitus; Shanghai Clinical Center for Diabetes, Shanghai, China
Correspondence: Dr Weiping Jia ([email protected]) or Dr Ruby Lai-chong Hoo ([email protected]).
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Ruby L.-C. Hoo
‡State Key Laboratory of Pharmaceutical Biotechnology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
§Department of Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
¶Research Center of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, University of Hong Kong, Hong Kong
Correspondence: Dr Weiping Jia ([email protected]) or Dr Ruby Lai-chong Hoo ([email protected]).
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Publisher: Portland Press Ltd
Received:
January 26 2015
Revision Received:
May 20 2015
Accepted:
June 01 2015
Accepted Manuscript online:
June 10 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2015 Authors; published by Portland Press Limited
2015
Clin Sci (Lond) (2015) 129 (7): 547–559.
Article history
Received:
January 26 2015
Revision Received:
May 20 2015
Accepted:
June 01 2015
Accepted Manuscript online:
June 10 2015
Citation
Mi Zhou, Yuqian Bao, Haobo Li, Yong Pan, Lingling Shu, Zhengyuan Xia, Donghai Wu, Karen S.L. Lam, Paul M. Vanhoutte, Aimin Xu, Weiping Jia, Ruby L.-C. Hoo; Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction. Clin Sci (Lond) 1 October 2015; 129 (7): 547–559. doi: https://doi.org/10.1042/CS20150073
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