title: Systemic inhibition of spontaneous calcification by the serum protein alpha 2-HS glycoprotein/fetuin.
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.
authors.affiliation: IZKF BIOMAT Klinikum der RWTH Aachen Pauwelsstr. 30 52074 Aachen, Germany. willi.jahnen@rwth-aachen.de
authors.forename: W
authors.initials: W
authors.lastname: Jahnen-Dechent
authors.forename: C
authors.initials: C
authors.lastname: Schäfer
authors.forename: A
authors.initials: A
authors.lastname: Heiss
authors.forename: J
authors.initials: J
authors.lastname: Grötzinger
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D000509:alpha-Fetoproteins / Q000235:genetics*
chemical_list: D000509:alpha-Fetoproteins; D002118:Calcium