Gas6 protein: its role in cardiovascular calcification

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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.

Autoři: Nadine Kaesler ^1*; Svenja Immendorf ¹; Chun Ouyang ¹; Marjolein Herfs ²; Nadja Drummen ²; Peter Carmeliet ³; Cees Vermeer ²; Jürgen Floege ¹; Thilo Krüger† ¹; Georg Schlieper† ¹
Působiště autorů: Uniklinik RWTH Aachen, Nephrology, Aachen, Germany. ¹; University of Maastricht, R&D Group, Maastricht, Netherlands. ²; University of Leuven, Vesalius Research Center, VIB, Leuven, Belgium. ³
Vyšlo v časopise: BMC Nefrol 2016, 17:52
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12882-016-0265-z

© The Author(s). 2016
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The electronic version of this article is the complete one and can be found online at: http://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-016-0265-z

Souhrn

Conclusions:
Taken together, in our study Gas6 fails to aggravate calcification against the previous assumption.

Zdroje

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