title: Role of SIRT3 in Angiotensin II-induced human umbilical vein endothelial cells dysfunction.
abstract: BACKGROUND
  SIRT3, a member of the sirtuin family of NAD(+)-dependent deacetylases, resides primarily in the mitochondria and has been shown to deacetylate several metabolic and respiratory enzymes that regulate important mitochondrial functions. Previous researches show an important role of SIRT3 in regulating the production of reactive oxygen species (ROS), and highlight the ability of SIRT3 to protect cells from oxidative damage. A key substance of renin-angiotensin-aldosterone system (RAAS), Angiotensin II (AngII) can induce cells dysfunction by increasing the production of ROS. In this paper, we focus on the role of SIRT3 in AngII-induced human umbilical vein endothelial cells (HUVECs) dysfunction.
  
  
  METHODS
  To study the influence of AngII on SIRT3 expression, HUVECs were treated with AngII of 10(-7), 10(-6), 10(-5) mol/L for 24 h. SIRT3 expression was detected by wester-blotting analysis and RT-PCR. In addition, to research the role of SIRT3 in AngII-induced HUVECs,we used SIRT3 siRNA to knock down SIRT3 expression in HUVECs. Cells pretreated with negative control siRNA or SIRT3 siRNA were exposed to AngII for 24 h, and endothelial nitric oxide synthase (eNOS) expression, eNOS activity, total level of nitric oxide (NO) and ROS generation of each group were detected.
  
  
  RESULTS
  Here we show that AngII treatment could increase generation of ROS, and decrease eNOS activity and total level of NO, while upregulated eNOS expression as a compensatory mechanism. The stimulation of AngII upregulated the expression of SIRT3 in HUVECs. SIRT3 siRNA worsen the AngII-induced effects above, besides, downregulated eNOS protein expression.
  
  
  CONCLUSIONS
  These data suggest that SIRT3 plays a role of protection in AngII-induced HUVECs dysfunction via regulation of ROS generation.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China. 649232246@qq.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China. chentongshuai@163.com.
authors.forename: Tongshuai
authors.initials: T
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China. 1322373569@qq.com.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China. 158362351@qq.com.
authors.forename: Shujian
authors.initials: S
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, 250012, Shandong Province, China. peili_bu@163.com.|Department of Cardiology, Qilu Hospital, Shandong University, No. 107 Wen Hua Xi Road, Jinan, 250012, Shandong Province, China. peili_bu@163.com.
authors.forename: Peili
authors.initials: P
authors.lastname: Bu
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D056566:Sirtuin 3 / Q000502:physiology*
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; C466093:SIRT3 protein, human; D056566:Sirtuin 3