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Modulation of cysteine-rich protein 2 expression in vascular injury and atherosclerosis

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Abstract

Vascular smooth muscle cells (VSMCs) of the arterial wall normally display a differentiated and contractile phenotype. In response to arterial injury, VSMCs switch to a synthetic phenotype, contributing to vascular remodeling. Cysteine-rich protein 2 (CRP2) is a cytoskeletal protein expressed in VSMCs and blunts VSMC migration in part by sequestering the scaffolding protein p130Cas at focal adhesions. CRP2 deficiency in mice increases neointima formation following arterial injury. The goal of this study was to use Csrp2 promoter-lacZ transgenic mice to analyze CRP2 expression during VSMC phenotypic modulation. In a neointima formation model after carotid artery cessation of blood flow, lacZ reporter activity and smooth muscle (SM) α-actin expression in the media were rapidly downregulated 4 days after carotid ligation. Fourteen days after ligation, there was a high level expression of both Csrp2 promoter activity and SM α-actin protein expression in neointimal cells. In atherosclerosis prone mice fed an atherogenic diet, Csrp2 promoter activity was detected within complex atherosclerotic lesions. Interestingly, Csrp2 promoter activity was also present in the fibrous caps of complicated atherosclerotic lesions, indicating that CRP2 might contribute to plaque stability. These findings support the concept that CRP2 contributes to the phenotypic modulation of VSMCs during vascular disease. Modulating transcription to increase CRP2 expression during vascular injury might attenuate vascular remodeling. In addition, increased CRP2 expression at the fibrous caps of advanced lesions might also serve to protect atherosclerotic plaques from rupture.

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Acknowledgments

This work was supported by grants from the National Science Council, Taiwan (101-2320-B-400-002-MY3 to S.-F.Y.), National Health Research Institutes (CS-103-PP-05 to S.-F.Y.), and the National Institutes of Health (HL-078869 to M.D.L.). This research was conducted under the Graduate Program of Biotechnology in Medicine sponsored by the National Tsing Hua University and the National Health Research Institutes. We thank the Pathology Core Laboratory of the National Health Research Institutes for processing and embedding of tissue samples. We thank Wun-Chu Fan for assistance in histological analysis.

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Authors and Affiliations

  1. Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan, Taiwan

    Chung-Huang Chen, Hua-Hui Ho, Meng-Ling Wu & Shaw-Fang Yet

  2. Institute of Bioinformatics and Structural Biology and Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan

    Chung-Huang Chen

  3. Institute of Molecular Medicine, National Tsing Hua University, Hsinchu, Taiwan

    Meng-Ling Wu

  4. Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA

    Matthew D. Layne

  5. Metabolomic Research Center, China Medical University Hospital and Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan

    Shaw-Fang Yet

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  1. Chung-Huang Chen
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  2. Hua-Hui Ho
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  4. Matthew D. Layne
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  5. Shaw-Fang Yet
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Correspondence to Shaw-Fang Yet.

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Chen, CH., Ho, HH., Wu, ML. et al. Modulation of cysteine-rich protein 2 expression in vascular injury and atherosclerosis. Mol Biol Rep 41, 7033–7041 (2014). https://doi.org/10.1007/s11033-014-3591-x

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