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- Title
Cbx3 inhibits vascular smooth muscle cell proliferation,migration, and neointima formation.
- Authors
Cheng Zhang; Dan Chen; Maguire, Eithne Margaret; Shiping He; Jiangyong Chen; Weiwei An; Mei Yang; Tayyab Adeel Afzal; Le Anh Luong; Li Zhang; Han Lei; Qingchen Wu; Qingzhong Xiao
- Abstract
Aims: To investigate the role of chromobox protein homolog 3 (Cbx3) in vascular smooth muscle cell (VSMC) proliferation, migration, and neointima formation following vascular injury. Methods And Results: Overexpression of Cbx3 led to a significant increase in VSMC contractile gene expression and VSMC apoptosis as well as a dramatic decrease in collagen gene expression, VSMC proliferation, and migration. Meanwhile, the opposite was observed following inhibition of endogenous Cbx3. Luciferase activity assays revealed that Notch signalling, but neither β-catenin nor NF-κB signalling, is regulated by Cbx3 in VSMCs, and among the four Notch receptors, Notch3 is selectively down-regulated by Cbx3 through a transcriptional repression mechanism. Notch3 gene activation recapitulates the effects of Cbx3 knockdown on VSMC proliferation and migration. Consequently, the inhibitory effects of Cbx3 over-expression on VSMC proliferation and migration were reversed by Notch3 gene reactivation. In a model of vascular damage by carotid wire injury, we observed that Cbx3 expression was dramatically down-regulated in the injured arteries. Local ectopic over-expression of Cbx3 in the injured arteries significantly inhibited Notch3 expression, thereby reducing VSMCs proliferation and causing an overall decrease in neointima formation. Additionally, injury-induced neointimal SMC hyperplasia was significantly reduced by aortic inhibition of Notch3. Importantly, a decreased expression level of Cbx3, but an increased expression level of Notch3, was observed in human femoral arteries with atherosclerotic lesions. Conclusion: Cbx3 modulates VSMC contractile and collagen gene expression, as well as VSMC proliferation, migration, and apoptosis via a Notch3 pathway, and plays an important role in controlling injury-induced neointima formation.
- Subjects
VASCULAR smooth muscle physiology; CELL differentiation; PROTEIN expression; MUSCLE cells; APOPTOSIS; NOTCH signaling pathway
- Publication
Cardiovascular Research, 2018, Vol 114, Issue 3, p443
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1093/cvr/cvx236