title: Gas6 protein: its role in cardiovascular calcification.
abstract: Cardiovascular calcifications can be prevented by vitamin K and are accelerated by vitamin K antagonists. These effects are believed to be mainly mediated by the vitamin K-dependent matrix Gla protein. Another vitamin K-dependent protein, Gas6, is also expressed in vascular smooth muscle cells (VSMC). In vitro Gas6 expression was shown to be regulated in VSMC calcification and apoptotic processes.
  
  
  
  We investigated the role of Gas6 in vitro using VSMC cultures and in vivo in young and old Gas6-deficient (Gas6(-/-)) and wildtype (WT) mice. In addition, Gas6(-/-) and WT mice were challenged by (a) warfarin administration, (b) uninephrectomy (UniNX) plus high phosphate diet, or (c) UniNX plus high phosphate plus electrocautery of the residual kidney.
  
  
  
  In vitro VSMC from WT and Gas6(-/-) mice exposed to warfarin showed increased apoptosis and calcified similarly. In vivo, aortic, cardiac and renal calcium content in all groups was similar, except for a lower cardiac calcium content in Gas6(-/-) mice (group a). Von Kossa staining revealed small vascular calcifications in both WT and Gas6(-/-) mice (groups a-c). In aging, non-manipulated mice, no significant differences in vascular calcification were identified between Gas6(-/-) and WT mice. Gas6(-/-) mice exhibited no upregulation of matrix Gla protein in any group. Cardiac output was similar in all treatment groups.
  
  
  
  Taken together, in our study Gas6 fails to aggravate calcification against the previous assumption.
authors.affiliation: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany. nkaesler@ukaachen.de.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kaesler
authors.affiliation: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Immendorf
authors.affiliation: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany.
authors.forename: Chun
authors.initials: C
authors.lastname: Ouyang
authors.affiliation: University of Maastricht, R&D Group, Maastricht, Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Herfs
authors.affiliation: University of Maastricht, R&D Group, Maastricht, Netherlands.
authors.forename: Nadja
authors.initials: N
authors.lastname: Drummen
authors.affiliation: University of Leuven, Vesalius Research Center, VIB, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.affiliation: University of Maastricht, R&D Group, Maastricht, Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Krüger
authors.affiliation: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Schlieper
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002114:Calcinosis / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002302:Cardiac Output; D002478:Cells, Cultured; D004032:Diet; D004452:Echocardiography; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D009392:Nephrectomy; D010710:Phosphates / Q000008:administration & dosage; D014859:Warfarin / Q000494:pharmacology; D000097568:Matrix Gla Protein; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D000925:Anticoagulants; D002118:Calcium; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D010710:Phosphates; D014859:Warfarin; D000097568:Matrix Gla Protein; D000099255:Growth Arrest-Specific Protein 6