title: Progressive thermopreconditioning attenuates rat cardiac ischemia/reperfusion injury by mitochondria-mediated antioxidant and antiapoptotic mechanisms.
abstract: OBJECTIVE
  Progressive thermal preconditioning (PTP) provides vascular protection with less hemodynamic fluctuations, endoplasmic reticulum (ER), and oxidative stress compared with whole body hyperthermia. We suggest PTP might efficiently diminish cardiac ischemia/reperfusion-induced apoptosis and autophagy injury.
  
  
  METHODS
  A total of 67 male Wistar rats were divided into a non-PTP control group, 24 or 72 hours after a single cycle or 3 consecutive cycles of PTP in a 42°C water bath (1-24, 1-72, 3-24, and 3-72 groups). We measured the cardiac O2(-) amount in vivo in response to left anterior descending coronary artery ligation for 2 hours and reperfusion for 3 hours. Cardiac function and injury were determined by microcirculation, electrocardiography, and infarct size. The PTP-induced protective effects on nicotinamide adenine dinucleotide phosphate oxidase gp91-mediated oxidative stress, ER stress, and apoptosis- and autophagy-related mechanisms were examined using Western blot and immunohistochemistry.
  
  
  RESULTS
  Coronary arterial ischemia/reperfusion depressed cardiac microcirculation, induced ST-segment elevation and increased infarct size in non-PTP and PTP rats. Ischemia/reperfusion enhanced the cardiac O2(-) levels by enhanced nicotinamide adenine dinucleotide phosphate oxidase gp91 expression, cytosolic cytochrome C release, and decreased mitochondrial Bcl-2 expression. Cardiac injury activated ER stress-78-kDa glucose-regulated protein expression, increased the Bax/Bcl-2 ratio, cleaved caspase 3 expression and poly-(ADP-ribose)-polymerase fragments, leading to apoptosis formation, and promoted LC3-II expression, resulting in autophagy formation. PTP treatment elevated heat shock protein 70, heat shock protein 32, Bcl-2, Bcl-xL, and manganese superoxide dismutase in the rat heart, especially in the 3-72 group. PTP treatment significantly restored cardiac microcirculation, decreased oxidative stress, ER stress, apoptosis, autophagy, and infarct size.
  
  
  CONCLUSIONS
  PTP significantly reduced cardiac ischemia/reperfusion injury by upregulating antioxidant, antiapoptotic, and antiautophagic mechanisms.
authors: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China; Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan, Republic of China; Mackay Medicine, Nursing and Management College, New Taipei City, Taiwan, Republic of China.
authors: Chen-Yen
authors: CY
authors: Chien
authors: Department of Biological Science, National Taiwan Normal University, Taipei, Taiwan, Republic of China. Electronic address: ctchien@ntnuh.edu.tw.
authors: Chiang-Ting
authors: CT
authors: Chien
authors: Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, Republic of China.
authors: Shoei-Shen
authors: SS
authors: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D006979:Hyperthermia, Induced; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008833:Microcirculation; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000473:pathology; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011652:Pulmonary Circulation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species