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Related Experiment Video

Updated: Oct 4, 2025

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
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PCSK9 promotes arterial medial calcification.

Maria Giovanna Lupo1, Alessandro Bressan1, Maristella Donato2

  • 1Dipartimento di Medicina, Università degli Studi di Padova, Padua, Italy.

Atherosclerosis
|February 9, 2022
PubMed
Summary

This study shows that impaired kidney function increases PCSK9, a protein that directly promotes vascular calcification in smooth muscle cells. This process involves extracellular vesicles carrying calcium and alkaline phosphatase, highlighting a new mechanism in chronic kidney disease complications.

Keywords:
CalcificationChronic kidney diseasePCSK9Smooth muscle cellsVescicles

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Area of Science:

  • Nephrology
  • Cardiology
  • Biochemistry

Background:

  • Chronic kidney disease (CKD) is linked to lipid metabolism issues and aortic calcification.
  • The specific role of kidney function in PCSK9 levels and vascular calcification is not fully understood.

Purpose of the Study:

  • To investigate how kidney function influences PCSK9 levels.
  • To determine PCSK9's direct effect on smooth muscle cell (SMC) calcification.

Main Methods:

  • Analyzed a cohort of 594 subjects for associations between kidney function and PCSK9.
  • Induced uremic conditions in rats to study aortic calcification and PCSK9 levels.
  • Overexpressed PCSK9 in human and rat SMCs and exposed them to high inorganic phosphate levels.
  • Investigated the role of extracellular vesicles (EVs) in PCSK9-mediated calcification.

Main Results:

  • Lower glomerular filtration rate correlated with higher plasma PCSK9.
  • Uremic rats showed increased aortic calcification, cholesterol, and PCSK9.
  • SMCs overexpressing PCSK9 exhibited increased calcium deposition and altered expression of calcification markers.
  • PCSK9-overexpressing SMCs released EVs enriched in calcium and alkaline phosphatase.

Conclusions:

  • PCSK9 plays a direct role in vascular calcification, particularly under high inorganic phosphate conditions linked to renal impairment.
  • The pro-calcific effect of PCSK9 in SMCs is mediated by altered cellular phenotype and the release of EVs containing calcium and alkaline phosphatase.