title: Extracellular matrix calcification in chronic kidney disease.
abstract: OBJECTIVE
  Extracellular matrix (ECM) mineralization occurring in soft tissues such as blood vessels is highly prevalent in patients with chronic kidney disease. This problem is now recognized as an active and regulated process involving a complex interaction of inducers and inhibitors. This review outlines new findings on calcification at the level of the ECM, with a focus on recent studies evaluating the pathogenesis of calcification of the vasculature.
  
  
  RESULTS
  Mechanisms promoting vascular calcification include dysregulation of mineral metabolism, especially high levels of phosphate and calcium, release of membrane-bound matrix vesicles from vascular smooth muscle cells (VSMCs), and formation of apoptotic bodies. Subsequent changes in the phenotype of VSMCs to osteoblast-like cells follow, inducing ECM formation and attracting local factors involved in the mineralization process (similar to the process of bone formation). Along with the loss of various calcification inhibitors, there is also likely a role for elastin and elastin-degrading enzymes, sodium-phosphate co-transporters, and the transmembrane protein klotho, as potential key regulators of ECM calcification.
  
  
  CONCLUSIONS
  Mechanisms of ECM calcification are not completely understood, although likely to be multifactorial. Increasing insight provides potential therapeutic options to reduce the burden of ectopic calcification and subsequent cardiovascular morbidity and mortality.
authors.affiliation: Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia bDepartment of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia. Nigel.Toussaint@wh.org.au
authors.forename: Nigel D
authors.initials: ND
authors.lastname: Toussaint
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D002114:Calcinosis / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D014652:Vascular Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology