title: Liraglutide alleviates diabetic cardiomyopathy by blocking CHOP-triggered apoptosis via the inhibition of the IRE-α pathway.
abstract: Clinically, diabetes mellitus is closely associated with and induces certain cardiovascular diseases. The aim of this study was to investigate endoplasmic reticulum (ER) stress-associated apoptosis of diabetic cardiomyopathy (DCM), and explore the protective mechanism of liraglutide. The DCM model was established with a high-fat diet and streptozotocin (STZ). Cardiac function was detected by echocardiogram examination and hematoxylin-eosin staining. ER stress unfolded protein response (UPR) hallmarks [inositol-requiring enzyme-α (IRE-α), p-Perk and ATF6] and transcription factors were detected with western blotting. Apoptosis inducers CHOP, c-Jun amino terminal kinase (JNK) and casapse-12 were also examined with western blotting. The results indicated that liraglutide is capable of improving cardiac function in DCM rats (P<0.05). IRE-α expression was significantly increased in the DCM group compared with the control group (P<0.05), and liraglutide is capable of decreasing IRE-α expression. X-box transcription factor-1 (XBP-1) was significantly spliced in the model group, and downregulated in the liraglutide-treated group. CHOP protein was upregulated in the DCM group, but inactivated by liraglutide treatment. In conclusion, liraglutide is capable of protecting DCM and blocking CHOP-mediated ER stress by inhibiting the IRE-α UPR pathway.
authors.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an, Xi'an, Shaanxi 710002, P.R. China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an, Xi'an, Shaanxi 710002, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Medicine, The Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China.
authors.forename: Tianzhi
authors.initials: T
authors.lastname: Cai
authors.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an, Xi'an, Shaanxi 710002, P.R. China.
authors.forename: Pengkang
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an, Xi'an, Shaanxi 710002, P.R. China.
authors.forename: Manli
authors.initials: M
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism*; D005215:Fasting / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000069450:Liraglutide; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051742:Transcription Factor CHOP; D014463:Ultrasonography
chemical_list: D001786:Blood Glucose; C575026:Ern1 protein, rat; D009097:Multienzyme Complexes; D051742:Transcription Factor CHOP; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases