title: Growth differentiation factor 15 may protect the myocardium from no‑reflow by inhibiting the inflammatory‑like response that predominantly involves neutrophil infiltration.
abstract: The aim of the current study was to investigate the time course of the expression of growth differentiation factor‑15 (GDF‑15) in rat ischemic myocardium with increasing durations of reperfusion, and to elucidate its physiopathological role in the no‑reflow phenomenon. Wistar rats were randomly divided into ischemia reperfusion (I/R) and sham groups, and myocardial I/R was established by ligation of the left anterior descending coronary artery for 1 h followed by reperfusion for 2, 4, 6, 12, 24 h and 7 days whilst rats in the sham group were subjected to a sham operation. The expression levels of GDF‑15 and ICAM‑1 were measured, in addition to myeloperoxidase (MPO) activity. The myocardial anatomical no‑reflow and infarction areas were assessed. The area at risk was not significantly different following various periods of reperfusion, while the infarct area and no‑reflow area were significantly greater following 6 h of reperfusion (P<0.05). The mRNA and protein expression levels of GDF‑15 were increased during the onset and development of no‑reflow, and peaked following 24 h of reperfusion. MPO activity was reduced with increasing reperfusion duration, while ICAM‑1 levels were increased. Hematoxylin and eosin staining demonstrated that myocardial neutrophil infiltration was significantly increased by I/R injury, in particular following 2, 4 and 6 h of reperfusion. GDF‑15 expression levels were negatively correlated with MPO activity (r=‑0.55, P<0.001), and the MPO activity was negatively correlated with the area of no‑reflow (r=‑0.46, P<0.01). By contrast, GDF‑15 was significantly positively correlated with ICAM‑1 levels (r=0.52, P<0.01), which additionally were demonstrated to be significantly positively associated with the size of the no‑reflow area (r=0.39, P<0.05). The current study demonstrated the time course effect of reperfusion on the expression of GDF‑15 in the myocardial I/R rat model, with the shorter reperfusion times (6 h) resulting in significant no‑reflow in ischemic myocardium. GDF‑15 may protect the I/R myocardium from no‑reflow by inhibiting the inflammatory‑like response, which involves neutrophil infiltration and transendothelial migration.
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China.
authors.forename: Kunying
authors.initials: K
authors.lastname: Pan
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China.
authors.forename: Qianping
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China.
authors.forename: Tiemin
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, The Affiliated Hospital of Logistics University of Chinese People's Armed Police Force, Tianjin 300162, P.R. China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D002316:Cardiotonic Agents / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D020556:Neutrophil Infiltration; D054318:No-Reflow Phenomenon / Q000378:metabolism* / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D013844:Thiazoles / Q000378:metabolism; D013997:Time Factors
chemical_list: D052160:Benzothiazoles; D002316:Cardiotonic Agents; D055436:Growth Differentiation Factor 15; D012333:RNA, Messenger; D013844:Thiazoles; D018799:Intercellular Adhesion Molecule-1; C009462:thioflavin T; D009195:Peroxidase