title: Role of CC-chemokine receptor 5 on myocardial ischemia-reperfusion injury in rats.
abstract: The expression level of CC-chemokine receptor 5 (CCR5) is enhanced post inflammatory stimulations and might play a crucial role on inflammatory cells infiltration post myocardial ischemia. The purpose of this study was to evaluate the role of CCR5 on myocardial ischemia-reperfusion (I/R) injury in rats. Adult male rats were randomized to sham group, I/R group (I/R, 30 min coronary artery occlusion followed by 2-h reperfusion), ischemic preconditioning (I/R + Pre), CCR5 antibody group [I/R + CCR5Ab (0.2 mg/kg)], and CCR5 agonist group [I/R + CCR5Ago, RNATES (0.1 mg/kg)], n = 12 each group. The serum level of creatine kinase (CK) and tumor necrosis factor α (TNF-α) were measured by ELISA. Myocardial infarction size and myeloperoxidase (MPO) activity were determined. Myocardial protein expression of CCR5 and intercellular adhesion molecule-1 (ICAM-1) were evaluated by Western blotting and immunohistochemistry staining, respectively. Myocardial nuclear factor-kappa B (NF-κB) activity was assayed by electrophoretic mobility shift assay. Myocardial CCR5 protein expression was significantly reduced in I/R + Pre group (P < 0.05 vs. I/R) and further reduced in I/R + CCR5Ab group (P < 0.05 vs. I/R + Pre). LVSP and ±dP/dt(max) were significantly lower while serum CK and TNF-α as well as myocardial MPO activity, ICAM-1 expression, and NF-κB activity were significantly higher in I/R group than in sham group (all P < 0.05), which were significantly reversed by I/R + Pre (all P < 0.05 vs. I/R) and I/R + CCR5Ab (all P < 0.05 vs. I/R + Pre) while aggravated by I/R + CCR5Ago (all P < 0.05 vs. I/R). Our results suggest that blocking CCR5 attenuates while enhancing CCR5 aggravates myocardial I/R injury through modulating inflammatory responses in rat heart.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People's Republic of China.
authors: Bo
authors: B
authors: Shen
authors: Jun
authors: J
authors: Li
authors: Ling
authors: L
authors: Gao
authors: Jieyu
authors: J
authors: Zhang
authors: Bo
authors: B
authors: Yang
mesh_terms: D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D006352:Heart Ventricles / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D019713:Receptors, CCR5 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D019713:Receptors, CCR5; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase; D003402:Creatine Kinase