Thoracic perivascular adipose tissue-derived PI16 alleviates vascular calcification via CKAP4/PI3K/Akt pathway

Shu Qiu1, Weixia Gao1, Dongxue Wu1

  • 1Department of Clinical Pharmacy, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

Insights

Thoracic perivascular adipose tissue (tPVAT) protects against medial arterial calcification (MAC). A protein called peptidase inhibitor 16 (PI16) from tPVAT inhibits MAC by interacting with CKAP4, offering a potential therapeutic target.

Area of Science:

  • Vascular Biology
  • Nephrology
  • Biochemistry

Background:

  • Medial arterial calcification (MAC) is a serious complication of chronic kidney disease (CKD), increasing cardiovascular risk.
  • Current treatments for MAC are limited, highlighting the need for new therapeutic strategies.
  • The role of thoracic perivascular adipose tissue (tPVAT) in regulating vascular calcification is not well understood.

Purpose of the Study:

  • To investigate the protective role of tPVAT against medial arterial calcification.
  • To identify the specific mechanisms by which tPVAT influences vascular calcification.

Main Methods:

  • Utilized experimental models of chronic kidney disease (CKD) and vitamin D3-induced vascular calcification.
  • Employed thoracic perivascular adipose tissue (tPVAT) transplantation and in vitro studies using vascular smooth muscle cells.
  • Identified key molecular factors and signaling pathways involved in the anti-calcific effects.

Main Results:

  • Thoracic aortas showed delayed medial calcification compared to abdominal aortas in experimental models.
  • Transplantation of tPVAT attenuated medial arterial calcification in the abdominal aorta.
  • Peptidase inhibitor 16 (PI16), derived from tPVAT, was identified as a crucial anti-calcific factor.
  • PI16 inhibits vascular smooth muscle cell calcification by interacting with CKAP4 and suppressing the PI3K/Akt/RUNX2 pathway.

Conclusions:

  • Thoracic perivascular adipose tissue (tPVAT) exerts a protective effect against medial arterial calcification.
  • Peptidase inhibitor 16 (PI16) is a key mediator of tPVAT's anti-calcific properties.
  • The PI16-CKAP4 signaling pathway represents a potential therapeutic target for treating vascular calcification in chronic kidney disease.

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