title: C1q/TNF-Related Protein 9 Protects Diabetic Rat Heart against Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress.
abstract: As a newly identified adiponectin paralog, C1q/TNF-related protein 9 (CTRP9) reduces myocardial ischemia reperfusion (IR) injury through partially understood mechanisms. In the present study, we sought to identify the role of endoplasmic reticulum stress (ERS) in CTRP9 induced cardioprotection in diabetic heart. Isolated hearts from high-fat-diet (HFD) induced type 2 diabetic Sprague-Dawley rats were subjected to ex vivo IR protocol via a Langendorff apparatus at the presence of globular CTRP9. CTRP9 significantly improved post-IR heart function and reduced cardiac infarction, cardiomyocytes apoptosis, Caspase-3, Caspase-9, Caspase-12, TNF-αexpression, and lactate dehydrogenase activity. The cardioprotective effect of CTRP9 was associated with reduced ERS and increased expression of disulfide-bond A oxidoreductase-like protein (DsbA-L) in diabetic heart. CTRP9 reduced ERS in thapsigargin (TG) treated cardiomyocytes and protected endoplasmic reticulum (ER) stressed H9c2 cells against simulated ischemia reperfusion (SIR) injury, concurrent with increased expression of DsbA-L. Knockdown of DsbA-L increased ERS and attenuated CTRP9 induced protection against SIR injury in H9c2 cells. Our findings demonstrated for the first time that CTRP9 exerts cardioprotection by reducing ERS in diabetic heart through increasing DsbA-L.
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Sanxing
authors: S
authors: Bai
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Liang
authors: L
authors: Cheng
authors: Department of Biomedical Engineering, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Xi'an 710038, China.
authors: Chongxi
authors: C
authors: Fan
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Dajun
authors: D
authors: Zhao
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Zhigang
authors: Z
authors: Qin
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Xiao
authors: X
authors: Feng
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Lin
authors: L
authors: Zhao
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Jipeng
authors: J
authors: Ma
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Xiaowu
authors: X
authors: Wang
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Jian
authors: J
authors: Yang
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Xuezeng
authors: X
authors: Xu
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Dinghua
authors: 0000-0001-8194-8837
authors: D
authors: Yi
authors: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an 710032, China.
authors: Wei
authors: 0000-0001-6478-6346
authors: W
authors: Yi
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000528:radiation effects; D000067268:Isolated Heart Preparation; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; D005982:Glutathione Transferase