title: PPARγ Inhibits VSMC Proliferation and Migration via Attenuating Oxidative Stress through Upregulating UCP2.
abstract: Increasing evidence showed that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are common event in the pathophysiology of many vascular diseases, including atherosclerosis and restenosis after angioplasty. Among the underlying mechanisms, oxidative stress is one of the principal contributors to the proliferation and migration of VSMCs. Oxidative stress occurs as a result of persistent production of reactive oxygen species (ROS). Recently, the protective effects of peroxisome proliferator-activated receptor γ (PPARγ) against oxidative stress/ROS in other cell types provide new insights to inhibit the suggests that PPARγ may regulate VSMCs function. However, it remains unclear whether activation of PPARγ can attenuate oxidative stress and further inhibit VSMC proliferation and migration. In this study, we therefore investigated the effect of PPARγ on inhibiting VSMC oxidative stress and the capability of proliferation and migration, and the potential role of mitochondrial uncoupling protein 2 (UCP2) in oxidative stress. It was found that platelet derived growth factor-BB (PDGF-BB) induced VSMC proliferation and migration as well as ROS production; PPARγ inhibited PDGF-BB-induced VSMC proliferation, migration and oxidative stress; PPARγ activation upregulated UCP2 expression in VSMCs; PPARγ inhibited PDGF-BB-induced ROS in VSMCs by upregulating UCP2 expression; PPARγ ameliorated injury-induced oxidative stress and intimal hyperplasia (IH) in UCP2-dependent manner. In conclusion, our study provides evidence that activation of PPARγ can attenuate ROS and VSMC proliferation and migration by upregulating UCP2 expression, and thus inhibit IH following carotid injury. These findings suggest PPARγ may represent a prospective target for the prevention and treatment of IH-associated vascular diseases.
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Ming-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Bing-Hu
authors.initials: BH
authors.lastname: Li
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pi
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Yin
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Long
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Meng-Jiao
authors.initials: MJ
authors.lastname: Sun
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Chang-Yue
authors.initials: CY
authors.lastname: Gao
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Jing-Cheng
authors.initials: JC
authors.lastname: Li
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D047495:PPAR gamma / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism / Q000502:physiology; D000071246:Uncoupling Protein 2 / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D047495:PPAR gamma; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2