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2016 ; 17
(1
): 52
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Gas6 protein: its role in cardiovascular calcification
#MMPMID27230889
Kaesler N
; Immendorf S
; Ouyang C
; Herfs M
; Drummen N
; Carmeliet P
; Vermeer C
; Floege J
; Krüger T
; Schlieper G
BMC Nephrol
2016[May]; 17
(1
): 52
PMID27230889
show ga
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.
|Aging/physiology
[MESH]
|Animals
[MESH]
|Anticoagulants/pharmacology
[MESH]
|Aorta/metabolism
[MESH]
|Apoptosis/drug effects/*genetics
[MESH]
|Calcinosis/*genetics/metabolism
[MESH]
|Calcium-Binding Proteins/metabolism
[MESH]
|Calcium/metabolism
[MESH]
|Cardiac Output
[MESH]
|Cells, Cultured
[MESH]
|Diet
[MESH]
|Echocardiography
[MESH]
|Extracellular Matrix Proteins/metabolism
[MESH]
|Female
[MESH]
|Heart/drug effects/*physiopathology
[MESH]
|Intercellular Signaling Peptides and Proteins/*genetics/metabolism
[MESH]