title: Exogenous H2S modulates mitochondrial fusion-fission to inhibit vascular smooth muscle cell proliferation in a hyperglycemic state.
abstract: OBJECTIVE
  Vascular smooth muscle cell (VSMC) proliferation in response to hyperglycemia is an important process in the development of arterial vessel hyperplasia. The shape change of mitochondria is dynamic and closely related to fission and fusion. Hydrogen sulfide (H2S) was confirmed to have anti-oxidative, anti-inflammatory and anti-proliferative effects. However, little it is known about its effects on mitochondrial morphology induced by hyperglycemia. The aim of the study is to demonstrate that H2S inhibits VSMC proliferation through regulating mitochondrial fission.
  
  
  RESULTS
  We observe lower H2S levels as well as higher proliferative protein expression levels for proliferative cell nuclear antigen (PCNA) and cyclin D1 and higher mitochondrial fusion-fission protein expression levels for dynamin-related protein 1 (Drp 1) in human kidney arteries and in db/db mouse aorta. Exogenous H2S (100 μM NaHS) inhibits vascular smooth muscle cells of human pulmonary aorta(HPASMC) proliferation and migration in response to high glucose using the BrdU and scratch wound repair assays, decreases proliferative protein (PCNA and cyclin D1) expression, and reduces ROS production in the cytoplasm and mitochondria. When HPASMCs proliferate with a high glucose treatment, the mitochondria become small spheres with a short rod-shaped structure, whereas NaHS, a mitochondrial division inhibitor and siDrp prevent VSMC proliferation and maintain mitochondria as stationary and randomly dispersed with fixed structures.
  
  
  CONCLUSIONS
  Exogenous H2S aids in inhibiting mitochondrial fragmentation and affects proliferation in db/db mice and HPASMCs by decreasing Drp 1 expression.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Aili
authors.initials: A
authors.lastname: Sun
authors.affiliation: Department of Urologic Surgery, First Clinical Medical School of Harbin Medical University, Harbin, 150001 China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Xiangjing
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Shiyun
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Jichao
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Fanghao
authors.initials: F
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, 150086 China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Zhang
keywords: Diabetes mellitus; Hydrogen sulfide (H2S); Proliferation; Vascular smooth muscle cell