title: Repetitive progressive thermal preconditioning hinders thrombosis by reinforcing phosphatidylinositol 3-kinase/Akt-dependent heat-shock protein/endothelial nitric oxide synthase signaling.
abstract: OBJECTIVE
  We compared the effects of modified progressive thermal preconditioning (PTP) and whole-body thermal preconditioning (TP) on stress responses, oxidative stress biomarkers, and arterial thrombosis formation, and explored their possible actions through phosphatidylinositol 3-kinase (PI3K)/Akt-dependent heat-shock protein (Hsp)/endothelial nitric oxide synthase (eNOS) pathways.
  
  
  METHODS
  We divided four groups of 249 male Wistar rats into nonimmersed controls, TP, and one (1-PTP) and three consecutive cycles (3-PTP) of PTP in a 42°C water bath. We evaluated the stress responses, including hemodynamics, total energy transfer, endoplasmic reticulum (ER) stress marker glucose-regulated protein (GRP78), and blood reactive oxygen species level during TP or PTP treatment. We compared 1-PTP, 3-PTP, or TP effects on oxidative stress, intercellular adhesion molecule 1 (ICAM-1), Hsp70, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) activity, and vascular phosphorylated Akt (p-Akt) and eNOS (p-eNOS) expressions in a model of topical ferric chloride (FeCl(3))-induced carotid artery thrombosis.
  
  
  RESULTS
  PTP significantly (P < .05) induced less hemodynamic fluctuations, total energy transfer, ER, and oxidative stress than TP did. After 24 or 72 hours of treatment, 1-PTP, 3-PTP, and TP significantly (P < .05) elevated carotid arterial Hsp70, p-Akt, and p-eNOS expression, significantly (P < .05) depressed FeCl(3)-enhanced vascular 2',7'-dichlorodihydrofluorescein diacetate, chemokine (C-X3-C motif) ligand 1 (CX3CL1), 3-nitrotyrosine, 4-hydroxynonenal, and ICAM-1 stain, PAI-1, and t-PA activity, leukocyte infiltration and thrombus size, and significantly (P < .05) delayed thrombus formation compared with controls. 3-PTP and TP had a higher (P < .05) protection than 1-PTP. PI3K/Akt, Hsp70, or N(G)-nitro-l-arginine methyl ester hydrochloride (L-NAME) inhibitors significantly (P < .05) depressed 3-PTP and TP-induced vascular protection.
  
  
  CONCLUSIONS
  Repetitive PTP is better than single PTP to hinder thrombosis formation via reinforcing PI3K/Akt-dependent Hsp70/eNOS signaling.
authors.affiliation: Department of Occupational Therapy, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Ping-Chia
authors.initials: PC
authors.lastname: Li
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Yang
authors.forename: Shih-Ping
authors.initials: SP
authors.lastname: Hsu
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016893:Carotid Stenosis / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006439:Hemodynamics; D006358:Hot Temperature; D015151:Immunoblotting; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D018384:Oxidative Stress; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013927:Thrombosis / Q000378:metabolism / Q000517:prevention & control*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D052250:Nitric Oxide Synthase Type III; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP