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2017 ; 2
(11
): ä Nephropedia Template TP
gab.com Text
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Myeloid-related protein-14 regulates deep vein thrombosis
#MMPMID28570273
Wang Y
; Gao H
; Kessinger CW
; Schmaier A
; Jaffer FA
; Simon DI
JCI Insight
2017[Jun]; 2
(11
): ä PMID28570273
show ga
Using transcriptional profiling of platelets from patients presenting with acute
myocardial infarction, we identified myeloid-related protein-14 (MRP-14, also
known as S100A9) as an acute myocardial infarction gene and reported that
platelet MRP-14 binding to platelet CD36 regulates arterial thrombosis. However,
whether MRP-14 plays a role in venous thrombosis is unknown. We subjected WT and
Mrp-14-deficient (Mrp-14-/-) mice to experimental models of deep vein thrombosis
(DVT) by stasis ligation or partial flow restriction (stenosis) of the inferior
vena cava. Thrombus weight in response to stasis ligation or stenosis was reduced
significantly in Mrp-14-/- mice compared with WT mice. The adoptive transfer of
WT neutrophils or platelets, or the infusion of recombinant MRP-8/14, into
Mrp-14-/- mice rescued the venous thrombosis defect in Mrp-14-/- mice, indicating
that neutrophil- and platelet-derived MRP-14 directly regulate venous
thrombogenesis. Stimulation of neutrophils with MRP-14 induced neutrophil
extracellular trap (NET) formation, and NETs were reduced in venous thrombi
harvested from Mrp-14-/- mice and in Mrp-14-/- neutrophils stimulated with
ionomycin. Given prior evidence that MRP-14 also regulates arterial thrombosis,
but not hemostasis (i.e., reduced bleeding risk), MRP-14 appears to be a
particularly attractive molecular target for treating thrombotic cardiovascular
diseases, including myocardial infarction, stroke, and venous thromboembolism.