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  3. The synergistic action of phosphate and interleukin-6 enhances senescence-associated calcification in vascular smooth muscle cells depending on p53

The synergistic action of phosphate and interleukin-6 enhances senescence-associated calcification in vascular smooth muscle cells depending on p53

  • Mech Ageing Dev. 2019 Sep;182:111124. doi: 10.1016/j.mad.2019.111124.
Deping Xu 1,  Fanjun Zeng 2,  Linzi Han 3,  Jun Wang 4,  Zongzhi Yin 5,  Liying Lv 6,  Liyu Guo 2,  Deguang Wang 7,  Yuanhong Xu 8,  Haisheng Zhou 9
Affiliations

Affiliations

  • 1 Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University (AHMU). No. 81 Meishan Rd., Hefei, China; Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China.
  • 2 Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China.
  • 3 Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China; Department of Nephrology, The Second Affiliated Hospital, AHMU. No. 678 Furong Rd., Hefei, China.
  • 4 Department of Nephrology, The Second Affiliated Hospital, AHMU. No. 678 Furong Rd., Hefei, China.
  • 5 Department of Obstetrics and Gynaecology, The First Affiliated Hospital, AHMU. No. 81 Meishan Rd., Hefei, China.
  • 6 Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University (AHMU). No. 81 Meishan Rd., Hefei, China.
  • 7 Department of Nephrology, The Second Affiliated Hospital, AHMU. No. 678 Furong Rd., Hefei, China. Electronic address: wangdeguang@ahmu.edu.cn.
  • 8 Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University (AHMU). No. 81 Meishan Rd., Hefei, China. Electronic address: xyhong1964@163.com.
  • 9 Department of Biochemistry & Molecular Biology, AHMU. No. 69 Meishan Rd., Hefei, China; Center for Scientific Research, AHMU. No. 81 Meishan Rd., Hefei, China. Electronic address: haishengs@ahmu.edu.cn.
PMID: 31376399 DOI: 10.1016/j.mad.2019.111124
Abstract

Cardiovascular calcification is associated with cardiovascular morbidity and mortality of patients with end-stage renal diseases (ESRD). Hyperphosphatemia and many of the inflammatory markers and mediators, including interleukin-6 (IL-6), are considered as the major risk factors of cardiovascular calcification. Although cellular senescence may be involved in cardiovascular calcification caused by phosphate overload and (or) IL-6 in patients with ESRD, less is known about the underlying mechanisms for phosphate- and IL-6-induced senescence-associated calcification of vascular smooth muscle cells (VSMCs). In the present study, we investigated the correlation between cellular senescence and vascular calcification induced by loading phosphate and (or) IL-6 in VSMCs. Our findings show that p53 plays a major role in senescence-associated vascular calcification induced by phosphate overload. IL-6 induces senescence-associated calcification in VSMCs depending upon activation of the IL-6/soluble IL-6 receptor (sIL-6R)/signal transducer and activator of transcription 3 (STAT3)/p53/p21 pathway. We demonstrate that the synergistic action of phosphate overload and IL-6 enhances senescence-associated calcification in a p53-dependent manner and is inhibited by an Anti-aging agent (resveratrol) in a dose-dependent manner.

Keywords

Calcification; IL-6; Phosphate; Senescence; p53.

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