Novel insights into uremic vascular calcification: role of matrix Gla protein and alpha-2-Heremans Schmid glycoprotein/fetuin.
Cardiovascular mortality is markedly increased in the dialysis population when compared to non-uremic subjects. Vascular and valvular calcifications are most frequently found in dialysis patients at risk and are independent predictors of cardiovascular death in this population. Traditionally, the presence of hyperphosphatemia and an increased calcium x phosphate product was considered a major pathomechanistic condition leading to excessive vascular and soft-tissue calcifications in uremic subjects. Recent studies in knockout mice, however, revealed that deficiencies in calcium-regulatory proteins may also directly contribute to the development of extraosseus calcifications. alpha(2)-Heremans Schmid glycoprotein and matrix Gla protein are important inhibitors of calcification in vivo and there is novel evidence available that a deficiency in such proteins is involved in the pathogenesis of cardiovascular calcifications in dialysis patients.
Ketteler
Markus
M
Department of Nephrology and Clinical Immunology, University Hospital Aachen, Germany. mketteler@ukaachen.de
Vermeer
Cees
C
Wanner
Christoph
C
Westenfeld
Ralf
R
Jahnen-Dechent
Willi
W
Floege
Jürgen
J
D000818:Animals; D001798:Blood Proteins / Q000172:deficiency / Q000502:physiology; D002114:Calcinosis / Q000209:etiology*; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000502:physiology; D003956:Dialysis; D016326:Extracellular Matrix Proteins; D006801:Humans; D014511:Uremia / Q000150:complications* / Q000378:metabolism; D014652:Vascular Diseases / Q000209:etiology; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein
D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein; C556354:AHSG protein, human; C556357:Ahsg protein, mouse