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Effect of sinomenine on vascular smooth muscle cell dedifferentiation and neointima formation after vascular injury in mice

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Abstract

Sinomenine, a pure alkaloid extract from Sinomenium acutum, has anti-inflammatory and immunoregulatory functions. This study investigated the efficiency and the signalling pathways involved in the effect of sinomenine on vascular smooth muscle cell (VSMC) dedifferentiation in response to platelet-derived growth factor (PDGF)-BB stimulation and vascular injury. VSMCs were isolated from rat aorta and preincubated with sinomenine before being stimulated with PDGF-BB. WST and BrdU incorporation assays were used to evaluate VSMC proliferation. Flow cytometric analysis was performed for testing the cell cycle progression. The cell migration of VSMCs were analysed using a Transwell system. The expression of VSMC specific genes and signalling proteins were tested by Western blot. For the animal study, C57/BL6 mice were fed either normal rodent chow diets or sinomenine chow diets that supplemented with 0.09 % sinomenine (w/w) in the normal chows for 14 days before carotid artery wire injury. PDGF-BB activated the dedifferentiation of VSMCs characterised by decreased expression of SMA, Smoothelin and SM22α. However, sinomenine treatment preserved the dedifferentiation in response to PDGF-BB. The activations of mitogen-activated protein kinase extracellular signal-regulated kinases, Akt, GSK3β and STAT3 induced by PDGF-BB were also inhibited in sinomenine-treated VSMCs. In vivo evidence with wire-injured mice exhibited a reduction in neointimal area and an increase in smooth muscle-specific gene expression in the sinomenine-treated group. In this study, we found that sinomenine-suppressed VSMC phenotype switching induced by PDGF-BB in vitro and neointimal formation in vivo. Therefore, sinomenine is a potential candidate to be used in the treatment of vascular proliferative disease.

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Acknowledgments

This work was supported by grants from Major Subject of Health Department of Hubei Province of China (No. JX4A02); The National Natural Science Foundation (No. 81000342); and Natural Science Foundation of Hubei Province of China; (No. 2010CDB06203).

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Authors and Affiliations

  1. Department of Cardiology, Renmin Hospital of Wuhan University, JieFang Road 238, Wuhan, 430060, People’s Republic of China

    Lihua Zhu, Hongjing Guan, Changping Cui, Song Tian, Da Yang, Xinan Wang, Shuming Zhang, Lang Wang & Hong Jiang

  2. Cardiovascular Research Institute of Wuhan University, Wuhan, 430060, People’s Republic of China

    Lihua Zhu, Hongjing Guan, Changping Cui, Song Tian, Da Yang, Xinan Wang, Shuming Zhang, Lang Wang & Hong Jiang

  3. Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China

    Yarong Hao

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  1. Lihua Zhu
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Correspondence to Hong Jiang.

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Lihua Zhu and Yarong Hao contributed equally to this work.

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Zhu, L., Hao, Y., Guan, H. et al. Effect of sinomenine on vascular smooth muscle cell dedifferentiation and neointima formation after vascular injury in mice. Mol Cell Biochem 373, 53–62 (2013). https://doi.org/10.1007/s11010-012-1474-9

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  • DOI: https://doi.org/10.1007/s11010-012-1474-9

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