High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size

• Published in: American journal of physiology. Heart and circulatory physiology 2016-01, Vol.310 (2), p.H279-H289
• Main Authors: Bourdier, Guillaume, Flore, Patrice, Sanchez, Hervé, Pepin, Jean-Louis, Belaidi, Elise, Arnaud, Claire
• Format: Article
• Language: English
• Subjects: Aerobiosis; Animals; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Blood Pressure; Caspase 3 - metabolism; Catecholamines - blood; Chronic Disease; Endoplasmic Reticulum Stress; Exercise; Heart attacks; HSP70 Heat-Shock Proteins; Hypoxia; Hypoxia - physiopathology; Kinases; Male; Membrane Proteins; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - pathology; Physical Conditioning, Animal; Physical Endurance; Rats; Rats, Wistar; Rodents; Size; Sleep Apnea, Obstructive - physiopathology; Training
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00448.2015

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.