title: Effects and underlying mechanisms of curcumin on the proliferation of vascular smooth muscle cells induced by Chol:MbetaCD.
abstract: Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of various cardiovascular diseases. Curcumin, extracted from Curcumae longae, has been shown a variety of beneficial effects on human health, including anti-atherosclerosis by mechanisms poorly understood. In the present study, we attempted to investigate whether curcumin has any effect on VSMCs proliferation and the potential mechanisms involved. Our data showed curcumin concentration-dependently abrogated the proliferation of primary rat VSMCs induced by Chol:MbetaCD. To explore the underlying cellular and molecular mechanisms, we found that curcumin was capable of restoring caveolin-1 expression which was reduced by Chol:MbetaCD treatment. Moreover, curcumin abrogated the increment of phospho-ERK1/2 and nuclear accumulation of ERK1/2 in primary rat VSMCs induced by Chol:MbetaCD, which led to a suppression of AP-1 promoter activity stimulated by Chol:MbetaCD. In addition, curcumin was able to reverse cell cycle progression induced by Chol:MbetaCD, which was further supported by its down-regulation of cyclinD1 and E2F promoter activities in the presence of Chol:MbetaCD. Taking together, our data suggest curcumin inhibits Chol:MbetaCD-induced VSMCs proliferation via restoring caveolin-1 expression that leads to the suppression of over-activated ERK signaling and causes cell cycle arrest at G1/S phase. These novel findings support the beneficial potential of curcumin in cardiovascular disease.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Yun-Bo
authors.initials: YB
authors.lastname: Yang
authors.forename: Qin-Hui
authors.initials: QH
authors.lastname: Tuo
authors.forename: Bing-Yang
authors.initials: BY
authors.lastname: Zhu
authors.forename: Lin-Xi
authors.initials: LX
authors.lastname: Chen
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D050684:E2F Transcription Factors / Q000378:metabolism; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D051242:Caveolin 1; D050684:E2F Transcription Factors; D047392:beta-Cyclodextrins; D019938:Cyclin D1; D002784:Cholesterol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D003474:Curcumin