Vascular Calcification Mechanisms: Updates and Renewed Insight into Signaling Pathways Involved in High Phosphate-Mediated Vascular Smooth Muscle Cell Calcification

Nima Abbasian

Research output: Contribution to journalReview articlepeer-review

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Abstract

Vascular calcification (VC) is associated with aging, cardiovascular and renal diseases and results in poor morbidity and increased mortality. VC occurs in patients with chronic kidney disease (CKD), a condition that is associated with high serum phosphate (Pi) and severe cardiovascular consequences. High serum Pi level is related to some pathologies which affect the behaviour of vascular cells, including platelets, endothelial cells (ECs) and smooth muscle cells (SMCs), and plays a central role in promoting VC. VC is a complex, active and cell-mediated process involving the transdifferentiation of vascular SMCs to a bone-like phenotype, systemic inflammation, decreased anti-calcific events (loss of calcification inhibitors), loss in SMC lineage markers and enhanced pro-calcific microRNAs (miRs), an increased intracellular calcium level, apoptosis, aberrant DNA damage response (DDR) and senescence of vascular SMCs. This review gives a brief overview of the current knowledge of VC mechanisms with a particular focus on Pi-induced changes in the vascular wall important in promoting calcification. In addition to reviewing the main findings, this review also sheds light on directions for future research in this area and discusses emerging pathways such as Pi-regulated intracellular calcium signaling, epigenetics, oxidative DNA damage and senescence-mediated mechanisms that may play critical, yet to be explored, regulatory and druggable roles in limiting VC.
Original languageEnglish
Article number804
Number of pages12
JournalBiomedicines
Volume9
Issue number7
DOIs
Publication statusPublished - 12 Jul 2021

Keywords

  • CKD
  • DNA damage
  • Epigenetic
  • MicroRNAs
  • Phosphate
  • Senescence
  • Signaling
  • Vascular calcification

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