Adiponectin protects rat myocardium against chronic intermittent hypoxia-induced injury via inhibition of endoplasmic reticulum stress.
Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5-6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.
Department of Respirology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Wenxiao
W
Ding
Department of Respirology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Xiaofeng
X
Zhang
Department of Respirology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Hanpeng
H
Huang
Department of Respirology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Ning
N
Ding
Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Shijiang
S
Zhang
Morsani College of Medicine, Tampa, Florida, United States of America.
Sean Z
SZ
Hutchinson
Department of Respirology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Xilong
X
Zhang
D052242:Adiponectin / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020169:Caspases / Q000378:metabolism; D004562:Electrocardiography; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy*; D020287:In Situ Nick-End Labeling; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects
D052242:Adiponectin; D002316:Cardiotonic Agents; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; C486557:Ern2 protein, rat; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases