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[Testosterone suppresses oxidized low-density lipoprotein-induced vascular smooth muscle cell phenotypic transition and proliferation].

Authors: Zhou, Wei  Liu, Wei  Liao, Hua  Cao, Zhe  Xie, Han  Zhang, Shaoying  Chen, Manhua 
Citation: Zhou W, etal., Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2015 Jun;31(6):775-8.
Pubmed: (View Article at PubMed) PMID:26062420

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.
CONCLUSION: 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.


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CRRD Object Information
CRRD ID: 13204747
Created: 2017-07-18
Species: All species
Last Modified: 2017-07-18
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.