The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification
Cora Schäfer, … , Thorsten Schinke, Willi Jahnen-Dechent
Cora Schäfer, … , Thorsten Schinke, Willi Jahnen-Dechent
Published August 1, 2003
Citation Information: J Clin Invest. 2003;112(3):357-366. https://doi.org/10.1172/JCI17202.
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Article Cardiology

The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification

Abstract

Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein α2–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.

Authors

Cora Schäfer, Alexander Heiss, Anke Schwarz, Ralf Westenfeld, Markus Ketteler, Jürgen Floege, Werner Müller-Esterl, Thorsten Schinke, Willi Jahnen-Dechent

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A mineral/vitamin D–rich diet leads to ectopic calcification in Ahsg–/– ...
A mineral/vitamin D–rich diet leads to ectopic calcification in Ahsg–/– mice. Ahsg+/+ and Ahsg–/– mice (mixed genetic background C57BL/6-129/Sv) were fed a mineral/vitamin D–rich diet for 4 months and analyzed for the presence of ectopic calcification. (a) Alizarin red staining of skeletal preparations. Note that calcified deposits depict small vessels in muscles along the vertebra in Ahsg–/– mice, but not in Ahsg+/+ mice. (b) von Kossa staining and counterstaining with safranin O of kidney and lung. Calcified lesions are stained black in renal tubules and interstitium and pulmonary alveoli of Ahsg–/– mice, but not in Ahsg+/+ mice.