BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Taken together, in our study Gas6 fails to aggravate calcification against the previous assumption.
BACKGROUND: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 VSMCcalcification and apoptotic processes. METHODS: 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. RESULTS: 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. CONCLUSIONS: Taken together, in our study Gas6 fails to aggravate calcification against the previous assumption.
Authors: A Angelillo-Scherrer; P de Frutos; C Aparicio; E Melis; P Savi; F Lupu; J Arnout; M Dewerchin; M Hoylaerts; J Herbert; D Collen; B Dahlbäck; P Carmeliet Journal: Nat Med Date: 2001-02 Impact factor: 53.440
Authors: P K Smith; R I Krohn; G T Hermanson; A K Mallia; F H Gartner; M D Provenzano; E K Fujimoto; N M Goeke; B J Olson; D C Klenk Journal: Anal Biochem Date: 1985-10 Impact factor: 3.365
Authors: Anne Angelillo-Scherrer; Laurent Burnier; Diether Lambrechts; Richard J Fish; Marc Tjwa; Stéphane Plaisance; Rocco Sugamele; Maria DeMol; Eduardo Martinez-Soria; Patrick H Maxwell; Greg Lemke; Stephen P Goff; Glenn K Matsushima; H Shelton Earp; Marc Chanson; Désiré Collen; Shozo Izui; Marc Schapira; Edward M Conway; Peter Carmeliet Journal: J Clin Invest Date: 2008-02 Impact factor: 14.808
Authors: Miles D Witham; Jennifer S Lees; Myra White; Margaret Band; Samira Bell; Donna J Chantler; Ian Ford; Roberta L Fulton; Gwen Kennedy; Roberta C Littleford; Ian V McCrea; Deborah McGlynn; Maurizio Panarelli; Maximilian R Ralston; Elaine Rutherford; Alison Severn; Nicola Thomson; Jamie P Traynor; Allan D Struthers; Kirsty Wetherall; Patrick B Mark Journal: J Am Soc Nephrol Date: 2020-08-13 Impact factor: 10.121
Authors: Juan Luis Carrillo-Linares; María Inmaculada García-Fernández; María José Morillo; Purificación Sánchez; José Rioja; Francisco Javier Barón; María José Ariza; Dominic J Harrington; David Card; Federica Boraldi; Daniela Quaglino; Pedro Valdivielso Journal: Front Med (Lausanne) Date: 2018-04-16