title: Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction.
abstract: 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 N(G)-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.
authors.affiliation: 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.
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Anesthesiology, LKS Faculty of Medicine, University of Hong Kong, Hong Kong.
authors.forename: Haobo
authors.initials: H
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yong
authors.initials: Y
authors.lastname: Pan
authors.affiliation: 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.
authors.forename: Lingling
authors.initials: L
authors.lastname: Shu
authors.affiliation: 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.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Key Laboratory of Regenerative Biology, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.affiliation: 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.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.affiliation: 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.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: 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 wpjia@sjtu.edu.cn rubyhoo@hku.hk.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.affiliation: 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 wpjia@sjtu.edu.cn rubyhoo@hku.hk.
authors.forename: Ruby L-C
authors.initials: RL
authors.lastname: Hoo
mesh_terms: D000818:Animals; D000838:Anions; D017209:Apoptosis; D001794:Blood Pressure; D003920:Diabetes Mellitus / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D017202:Myocardial Ischemia / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D015427:Reperfusion Injury; D013481:Superoxides / Q000378:metabolism
chemical_list: D000838:Anions; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D013481:Superoxides
keywords: adipocyte fatty-acid-binding protein; cardiac dysfunction; diabetes; endothelial nitric oxide synthase/nitric oxide (eNOS/NO) pathway; ischaemic heart disease; myocardial ischaemia/reperfusion