title: [Testosterone suppresses oxidized low-density lipoprotein-induced vascular smooth muscle cell phenotypic transition and proliferation].
abstract: OBJECTIVE
  To investigate the inhibitory effect of testosterone on oxidized low-density lipoproteins (ox-LDL)-stimulated phenotypic transition and proliferation of vascular smooth muscle cells (VSMCs) in vitro, and explore its possible mechanisms.
  
  
  METHODS
  Rat VSMCs were cultured using serum starvation method to make cell synchronization. Cells in vitro were divided into control group, ox-LDL group (treated with 50 μg/mL ox-LDL), FBS group (treated with 100 mL/L fetal bovine serum), and testosterone groups (treated respectively with 5×10(-8) and 5×10(-7) mol/L testosterone for 12 hours, followed by incubation with 50 μg/mL ox-LDL). The effect of testosterone on the ox-LDL-induced proliferation of VSMCs was explored by WST-1 assay. The cell cycle distribution was determined using flow cytometry. Western blotting was used to detect the expressions of mitofusin 2 (Mfn2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA) and osteopontin (OPN).
  
  
  RESULTS
  Compared with control group, the proliferation of VSMCs was promoted by ox-LDL, the number of VSMCs decreased in G0/G1 phase and increased in S phase significantly, the expression levels of Mfn2 and α-SMA were significant reduced, and the expression levels of p-ERK1/2, PCNA and OPN were significant raised in ox-LDL group. Compared with ox-LDL group, testosterone showed stronger inhibitory effect on the proliferation of VSMCs induced by ox-LDL, arrested most of the cells in the G0/G1 phase, ascended significantly the expression levels of Mfn2 and α-SMA, and descended significantly the expression levels of p-ERK1/2, PCNA and OPN in the two testosterone groups in a slight dose-dependent manner.
  
  
  CONCLUSIONS
  Testosterone can inhibit phenotypic transition and proliferation of VSMCs induced by ox-LDL in vitro, which may be related to the up-regulated expression of Mfn2 and the suppression on ERK1/2 pathway.
authors.affiliation: Department of Cardiology, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Geriatrics, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Cardiology, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Han
authors.initials: H
authors.lastname: Xie
authors.affiliation: Geriatrics, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Central Hospital of Wuhan, Wuhan 430014, China.
authors.forename: Manhua
authors.initials: M
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020558:GTP Phosphohydrolases; D005786:Gene Expression Regulation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D000199:Actins; D020558:GTP Phosphohydrolases; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053495:Osteopontin; D018809:Proliferating Cell Nuclear Antigen; D013739:Testosterone; C099252:oxidized low density lipoprotein; C498862:Acta2 protein, rat; C489710:Mfn2 protein, rat