Mechanistic Insights into Vascular Calcification in CKD

Rukshana Shroff*, David A. Long, Catherine Shanahan

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

309 Citations (Scopus)

Abstract

Cardiovascular disease begins early in the course of renal decline and is a life-limiting problem in patients with CKD. The increased burden of cardiovascular disease is due, at least in part, to calcification of the vessel wall. The uremic milieu provides a perfect storm of risk factors for accelerated calcification, but elevated calcium and phosphate levels remain key to the initiation and progression of vascular smooth muscle cell calcification in CKD. Vascular calcification is a highly regulated process that involves a complex interplay between promoters and inhibitors of calcification and has many similarities to bone ossification. Here, we discuss current understanding of the process of vascular calcification, focusing specifically on the discrete and synergistic effects of calcium and phosphate in mediating vascular smooth muscle cell apoptosis, osteochondrocytic differentiation, vesicle release, calcification inhibitor expression, senescence, and death. Using our model of intact human vessels, factors initiating vascular calcification in vivo and the role of calcium and phosphate in driving accelerated calcification ex vivo are described. This work allows us to link clinical and basic research into a working theoretical model to explain the pathway of development of vascular calcification in CKD. J Am Soc Nephrol 24: 179-189, 2013. doi: 10.1681/ASN.2011121191

Original languageEnglish
Pages (from-to)179-189
Number of pages11
JournalJournal of the American Society of Nephrology
Volume24
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • SMOOTH-MUSCLE-CELLS
  • CHRONIC KIDNEY-DISEASE
  • STAGE RENAL-DISEASE
  • CORONARY-ARTERY CALCIFICATION
  • MATRIX GLA PROTEIN
  • CHRONIC-HEMODIALYSIS PATIENTS
  • CALCIUM-SENSING RECEPTOR
  • BONE MORPHOGENETIC PROTEIN-2
  • IN-VITRO
  • EXTRACELLULAR CALCIUM

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