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Poly(ADP-ribose) polymerase 1 accelerates vascular calcification by upregulating Runx2

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  • Cheng Wang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Wenjing Xu

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Jie An

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Minglu Liang

    (Huazhong University of Science and Technology)

  • Yiqing Li

    (Huazhong University of Science and Technology)

  • Fengxiao Zhang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

  • Qiangsong Tong

    (Huazhong University of Science and Technology)

  • Kai Huang

    (Huazhong University of Science and Technology
    Huazhong University of Science and Technology)

Abstract

Vascular calcification is highly prevalent in end-stage renal diseases and is predictive of cardiovascular events and mortality. Poly(ADP-ribose) polymerase 1 (PARP1) inhibition or deletion is vasoprotective in several disease models. Here we show that PARP activity is increased in radial artery samples from patients with chronic renal failure, in arteries from uraemic rats, and in calcified vascular smooth muscle cells (VSMCs) in vitro. PARP1 deficiency blocks, whereas PARP1 overexpression exacerbates, the transdifferentiation of VSMCs from a contractile to an osteogenic phenotype, the expression of mineralization-regulating proteins, and calcium deposition. PARP1 promotes Runx2 expression, and Runx2 deficiency offsets the pro-calcifying effects of PARP1. Activated PARP1 suppresses miRNA-204 expression via the IL-6/STAT3 pathway and thus relieves the repression of its target, Runx2, resulting in increased Runx2 protein. Together, these results suggest that PARP1 counteracts vascular calcification and that therapeutic agents that influence PARP1 activity may be of benefit to treat vascular calcification.

Suggested Citation

  • Cheng Wang & Wenjing Xu & Jie An & Minglu Liang & Yiqing Li & Fengxiao Zhang & Qiangsong Tong & Kai Huang, 2019. "Poly(ADP-ribose) polymerase 1 accelerates vascular calcification by upregulating Runx2," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09174-1
    DOI: 10.1038/s41467-019-09174-1
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