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p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells

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Abstract

Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients. p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE–/– mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n = 20) and PCS-treated group (n = 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 μmol/L PCS for in vitro evaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.

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Authors and Affiliations

  1. Department of Cardiology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Hui Han, Yanjia Chen, Zhengbin Zhu, Xiuxiu Su, Jingwei Ni, Run Du, Ruiyan Zhang & Wei Jin

  2. Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Hui Han, Yanjia Chen & Ruiyan Zhang

Authors
  1. Hui Han
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  2. Yanjia Chen
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  3. Zhengbin Zhu
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  4. Xiuxiu Su
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  5. Jingwei Ni
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  6. Run Du
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  7. Ruiyan Zhang
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  8. Wei Jin
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Correspondence to Ruiyan Zhang or Wei Jin.

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These authors contributed equally to this work.

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Han, H., Chen, Y., Zhu, Z. et al. p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells. Front. Med. 10, 320–329 (2016). https://doi.org/10.1007/s11684-016-0463-x

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  • DOI: https://doi.org/10.1007/s11684-016-0463-x

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