The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification.
Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.
Schafer
Cora
C
Interdisciplinary Center for Clinical Research on Biochematerials, University Clinics, Aachen, Germany.
Heiss
Alexander
A
Schwarz
Anke
A
Westenfeld
Ralf
R
Ketteler
Markus
M
Floege
Jurgen
J
Muller-Esterl
Werner
W
Schinke
Thorsten
T
Jahnen-Dechent
Willi
W
D000818:Animals; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002114:Calcinosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002115:Calciphylaxis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D004032:Diet / Q000009:adverse effects; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008903:Minerals / Q000008:administration & dosage; D013045:Species Specificity; D014807:Vitamin D / Q000008:administration & dosage; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; C556357:Ahsg protein, mouse; D001798:Blood Proteins; D008903:Minerals; D060749:alpha-2-HS-Glycoprotein; D014807:Vitamin D