Calciprotein Particles Balancing Mineral Homeostasis and Vascular Pathology: Balancing Mineral Homeostasis and Vascular Pathology

Anton G Kutikhin*, Lian Feenstra, Alexander E Kostyunin, Arseniy E Yuzhalin, Jan-Luuk Hillebrands, Guido Krenning*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

59 Citations (Scopus)
127 Downloads (Pure)

Abstract

Hypercalcemia and hyperphosphatemia associate with an elevated risk of cardiovascular events, yet the pathophysiological basis of this association is unclear. Disturbed mineral homeostasis and the associated hypercalcemia and hyperphosphatemia may result in the formation of circulating calciprotein particles (CPPs) that aggregate the excessive calcium and phosphate ions. If not counteracted, the initially formed harmless amorphous spherical complexes (primary CPPs) may mature into damaging crystalline complexes (secondary CPPs). Secondary CPPs are internalized by vascular cells, causing a massive influx of calcium ions into the cytosol, leading to a proinflammatory response, cellular dysfunction, and cell death. Although the pathophysiological effects induced by CPPs in vascular cells receive increasing attention, a complete picture of how these particles contribute to the development of atherosclerosis and vascular calcification remains elusive. We here discuss existing knowledge on CPP formation and function in atherosclerosis and vascular calcification, techniques for investigating CPPs, and models currently applied to assess CPP-induced cardiovascular pathogenesis. Lastly, we evaluate the potential diagnostic value of serum CPP measurements and the therapeutic potential of anti-CPP therapies currently under development.

Original languageEnglish
Pages (from-to)1607-1624
Number of pages18
JournalArteriosclerosis, thrombosis, and vascular biology
Volume41
Issue number5
Early online date2021
DOIs
Publication statusPublished - 5-May-2021

Keywords

  • atherosclerosis
  • calcium
  • homeostasis
  • hypercalcemia
  • hyperphosphatemia
  • vascular calcification
  • SMOOTH-MUSCLE-CELLS
  • PERIVASCULAR ADIPOSE-TISSUE
  • SERUM CALCIFICATION PROPENSITY
  • BONE MORPHOGENETIC PROTEIN-2
  • CORONARY-ARTERY CALCIFICATION
  • CHRONIC KIDNEY-DISEASE
  • MATRIX GLA-PROTEIN
  • ALL-CAUSE MORTALITY
  • HUMAN-BODY FLUIDS
  • FETUIN-A

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