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Aberrant DNA methylation of the PDGF gene in homocysteine‑mediated VSMC proliferation and its underlying mechanism.
Mol Med Rep. 2014 Aug; 10(2):947-54.MM

Abstract

It is well established that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS), which is characterized by vascular smooth muscle cell (VSMC) proliferation. However, the molecular mechanism underlying AS in VSMCs is yet to be elucidated. The aim of this study was to investigate the potential involvement of aberrant DNA methylation of the platelet‑derived growth factor (PDGF) gene in Hcy‑mediated VSMC proliferation and its underlying mechanism. Cultured human VSMCs were treated with varying concentrations of Hcy. VSMC proliferation, PDGF mRNA and protein expression and PDGF promoter demethylation showed a dose‑dependent increase with Hcy concentration, suggesting an association among them. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase, indicating that VSMC proliferation was increased under Hcy treatment. Furthermore, S‑adenosylhomocysteine (SAH) levels were observed to increase and those of S‑adenosylmethionine (SAM) were observed to decrease. The consequent decrease in the ratio of SAM/SAH may partially explain the hypomethylation of PDGF with Hcy treatment. Folate treatment exhibited an antagonistic effect against Hcy‑induced VSMC proliferation, aberrant PDGF methylation and PDGF expression. These data suggest that Hcy may stimulate VSMC proliferation through the PDGF signaling pathway by affecting the epigenetic regulation of PDGF through the demethylation of its promoter region. These findings may provide novel insight into the molecular association between aberrant PDGF gene demethylation and the proliferation of VSMCs in Hcy‑associated AS.

Authors+Show Affiliations

Department of Laboratory Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Prenatal Diagnosis Center, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Laboratory Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Laboratory Medicine, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Center of Scientific Technology, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.Department of Pathophysiology, Basic Medical School, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24841643

Citation

Han, Xue-Bo, et al. "Aberrant DNA Methylation of the PDGF Gene in Homocysteine‑mediated VSMC Proliferation and Its Underlying Mechanism." Molecular Medicine Reports, vol. 10, no. 2, 2014, pp. 947-54.
Han XB, Zhang HP, Cao CJ, et al. Aberrant DNA methylation of the PDGF gene in homocysteine‑mediated VSMC proliferation and its underlying mechanism. Mol Med Rep. 2014;10(2):947-54.
Han, X. B., Zhang, H. P., Cao, C. J., Wang, Y. H., Tian, J., Yang, X. L., Yang, A. N., Wang, J., Jiang, Y. D., & Xu, H. (2014). Aberrant DNA methylation of the PDGF gene in homocysteine‑mediated VSMC proliferation and its underlying mechanism. Molecular Medicine Reports, 10(2), 947-54. https://doi.org/10.3892/mmr.2014.2249
Han XB, et al. Aberrant DNA Methylation of the PDGF Gene in Homocysteine‑mediated VSMC Proliferation and Its Underlying Mechanism. Mol Med Rep. 2014;10(2):947-54. PubMed PMID: 24841643.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aberrant DNA methylation of the PDGF gene in homocysteine‑mediated VSMC proliferation and its underlying mechanism. AU - Han,Xue-Bo, AU - Zhang,Hui-Ping, AU - Cao,Cheng-Jian, AU - Wang,Yan-Hua, AU - Tian,Jue, AU - Yang,Xiao-Ling, AU - Yang,An-Ning, AU - Wang,Jie, AU - Jiang,Yi-Deng, AU - Xu,Hua, Y1 - 2014/05/20/ PY - 2013/08/07/received PY - 2014/04/08/accepted PY - 2014/5/21/entrez PY - 2014/5/21/pubmed PY - 2015/2/13/medline SP - 947 EP - 54 JF - Molecular medicine reports JO - Mol Med Rep VL - 10 IS - 2 N2 - It is well established that homocysteine (Hcy) is an independent risk factor for atherosclerosis (AS), which is characterized by vascular smooth muscle cell (VSMC) proliferation. However, the molecular mechanism underlying AS in VSMCs is yet to be elucidated. The aim of this study was to investigate the potential involvement of aberrant DNA methylation of the platelet‑derived growth factor (PDGF) gene in Hcy‑mediated VSMC proliferation and its underlying mechanism. Cultured human VSMCs were treated with varying concentrations of Hcy. VSMC proliferation, PDGF mRNA and protein expression and PDGF promoter demethylation showed a dose‑dependent increase with Hcy concentration, suggesting an association among them. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase, indicating that VSMC proliferation was increased under Hcy treatment. Furthermore, S‑adenosylhomocysteine (SAH) levels were observed to increase and those of S‑adenosylmethionine (SAM) were observed to decrease. The consequent decrease in the ratio of SAM/SAH may partially explain the hypomethylation of PDGF with Hcy treatment. Folate treatment exhibited an antagonistic effect against Hcy‑induced VSMC proliferation, aberrant PDGF methylation and PDGF expression. These data suggest that Hcy may stimulate VSMC proliferation through the PDGF signaling pathway by affecting the epigenetic regulation of PDGF through the demethylation of its promoter region. These findings may provide novel insight into the molecular association between aberrant PDGF gene demethylation and the proliferation of VSMCs in Hcy‑associated AS. SN - 1791-3004 UR - https://www.unboundmedicine.com/medline/citation/24841643/Aberrant_DNA_methylation_of_the_PDGF_gene_in_homocysteine‑mediated_VSMC_proliferation_and_its_underlying_mechanism_ L2 - http://www.spandidos-publications.com/mmr/10/2/947 DB - PRIME DP - Unbound Medicine ER -