title: CTRP9 induces mitochondrial biogenesis and protects high glucose-induced endothelial oxidative damage via AdipoR1 -SIRT1- PGC-1α activation.
abstract: Vascular lesions caused by endothelial dysfunction are the most common and serious complication of diabetes. The vasoactive potency of CTRP9 has been reported in our previous study via nitric oxide (NO) production. However, the effect of CTRP9 on vascular endothelial cells remains unknown. This study aimed to investigate the protection role of CTRP9 in the primary aortic vascular endothelial cells and HAECs under high-glucose condition. We found that the aortic vascular endothelial cells isolated from mice fed with a high fat diet generated more ROS production than normal cells, along with decreased mitochondrial biogenesis, which was also found in HAECs treated with high glucose. However, the treatment of CTPR9 significantly reduced ROS production and increased the activities of endogenous antioxidant enzymes, the expression of PGC-1α, NRF1, TFAM, ATP5A1 and SIRT1, and the activity of cytochrome c oxidase, indicating an induction of mitochondrial biogenesis. Furthermore, silencing the expression of SIRT1 in HAECs impeded the effect of CTRP9 on mitochondrial biogenesis, while silencing the expression of AdipoR1 in HAECs reversed the expression of SIRT1 and PGC-1α. Based on these findings, this study showed that CTRP9 might induce mitochondrial biogenesis and protect high glucose-induced endothelial oxidative damage via AdipoR1-SIRT1-PGC-1α signaling pathway.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China.
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032 China. Electronic address: qijunzheng123@163.com.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Zheng
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage*; D006023:Glycoproteins / Q000378:metabolism*; D051379:Mice; D001678:Organelle Biogenesis; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C534692:CTRP9 protein, mouse; D006023:Glycoproteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D017382:Reactive Oxygen Species; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose
keywords: AdipoR1; CTRP9; Mitochondrial biogenesis; PGC-1α; SIRT1