title: High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size.
abstract: Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients.
authors.affiliation: Grenoble Alpes University, HP2 Laboratory, Grenoble, France; Institut National de la Santé et de la Recherche Médicale, U1042, Grenoble, France; and.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourdier
authors.affiliation: Grenoble Alpes University, HP2 Laboratory, Grenoble, France; Institut National de la Santé et de la Recherche Médicale, U1042, Grenoble, France; and.
authors.forename: Patrice
authors.initials: P
authors.lastname: Flore
authors.affiliation: Institut de Recherche Biomédicale des Armées, Operational Environments, Brétigny/Orge, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Sanchez
authors.affiliation: Grenoble Alpes University, HP2 Laboratory, Grenoble, France; Institut National de la Santé et de la Recherche Médicale, U1042, Grenoble, France; and.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Pepin
authors.affiliation: Grenoble Alpes University, HP2 Laboratory, Grenoble, France; Institut National de la Santé et de la Recherche Médicale, U1042, Grenoble, France; and.
authors.forename: Elise
authors.initials: E
authors.lastname: Belaidi
authors.affiliation: Grenoble Alpes University, HP2 Laboratory, Grenoble, France; Institut National de la Santé et de la Recherche Médicale, U1042, Grenoble, France; and claire.arnaud@ujf-grenoble.fr.
authors.forename: Claire
authors.identifier: http://orcid.org/0000-0003-0964-9423
authors.initials: C
authors.lastname: Arnaud
mesh_terms: D000332:Aerobiosis; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001794:Blood Pressure; D053148:Caspase 3 / Q000378:metabolism; D002395:Catecholamines / Q000097:blood; D002908:Chronic Disease; D059865:Endoplasmic Reticulum Stress; D018840:HSP70 Heat-Shock Proteins; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins; D009203:Myocardial Infarction / Q000473:pathology* / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D051381:Rats; D017208:Rats, Wistar; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D002395:Catecholamines; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: endoplasmic reticulum stress; high-intensity aerobic training; intermittent hypoxia; ischemia-reperfusion; obstructive sleep apnea