1. Gas6 protein: its role in cardiovascular calcification.
- Author
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Kaesler N, Immendorf S, Ouyang C, Herfs M, Drummen N, Carmeliet P, Vermeer C, Floege J, Krüger T, and Schlieper G
- Subjects
- Aging physiology, Animals, Anticoagulants pharmacology, Aorta metabolism, Apoptosis drug effects, Calcinosis metabolism, Calcium metabolism, Calcium-Binding Proteins metabolism, Cardiac Output, Cells, Cultured, Diet, Echocardiography, Extracellular Matrix Proteins metabolism, Female, Heart drug effects, Intercellular Signaling Peptides and Proteins metabolism, Kidney metabolism, Mice, Mice, Inbred C57BL, Myocardium metabolism, Nephrectomy, Phosphates administration & dosage, Warfarin pharmacology, Matrix Gla Protein, Apoptosis genetics, Calcinosis genetics, Heart physiopathology, Intercellular Signaling Peptides and Proteins genetics, Muscle, Smooth, Vascular drug effects
- Abstract
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.
- Published
- 2016
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