Systemic inhibition of spontaneous calcification by the serum protein alpha 2-HS glycoprotein/fetuin

Z Kardiol. 2001;90 Suppl 3:47-56. doi: 10.1007/pl00022849.

Abstract

The extracellular fluid is a metastable system with regard to calcium and phosphate ions. Active inhibitors of calcification must be present in serum to prevent the spontaneous formation of Ca2+.Pi solid phases which could otherwise precipitate to cause renal calcinosis and block small blood vessels. alpha 2-HS glycoproteins/fetuins, AHSGs, are ideal candidates for this function. AHSGs are ubiquitous and highly abundant in serum; they bind calcium and efficiently prevent de novo formation of apatitic mineral. Normocalcemic AHSG-deficient mice develop sporadic perivascular calcification. Hypercalcemia induced by dietary means or by hormone treatment results in lethal calcinosis in Ahsg-/-mice. A mineral binding structure is proposed for domain D1 of AHSG suggesting that the proposed EF-hand motif for calcium binding does not exist in AHSG. Unlike serum albumin, AHSG does not preferentially bind ionic Ca2+, but rather in the form of apatitic microcrystals.

MeSH terms

  • Animals
  • Arteriosclerosis / genetics*
  • Calcinosis / genetics*
  • Calcium / metabolism
  • Gene Expression / physiology
  • Mice
  • Mice, Knockout
  • alpha-Fetoproteins / genetics*

Substances

  • alpha-Fetoproteins
  • Calcium