The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification

J Clin Invest. 2003 Aug;112(3):357-66. doi: 10.1172/JCI17202.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Proteins / deficiency
  • Blood Proteins / genetics
  • Blood Proteins / physiology*
  • Calcinosis / blood
  • Calcinosis / etiology
  • Calcinosis / pathology
  • Calcinosis / prevention & control*
  • Calciphylaxis / blood
  • Calciphylaxis / etiology
  • Calciphylaxis / prevention & control
  • Diet / adverse effects
  • Female
  • Humans
  • Kidney Failure, Chronic / complications
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Minerals / administration & dosage
  • Species Specificity
  • Vitamin D / administration & dosage
  • alpha-2-HS-Glycoprotein

Substances

  • AHSG protein, human
  • Ahsg protein, mouse
  • Blood Proteins
  • Minerals
  • alpha-2-HS-Glycoprotein
  • Vitamin D