Hypercoagulability associated with increased von Willebrand Factor secretion from vascular endothelium by elevated NaCl: possible mechanism for increased risk of thrombosis caused by dehydration.

Thursday, November 07, 2013 — Poster Session II
12:00 p.m. – 2:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NHLBI	CHEMCELL-6

Authors

N.I. Dmitrieva
M.B. Burg

Abstract

Hypercoagulable state increases risk of cardiovascular events due to thrombus formation. Dehydration and hypernatremia are associated with thrombosis, but the mechanisms are not clear. Von Willebrand Factor is secreted by endothelium affecting platelets aggregation and promoting activation of coagulation cascade and thrombus formation. Here we show, that in culture of primary Human Umbilical Vein Endothelia Cells, elevating medium osmolality to 320-380 mosmol/kg by adding NaCl reversibly increases both vWF mRNA and vWF secretion. To elevate NaCl in vivo, we modeled mild dehydration by subjecting mice to water restriction (WR) for 9 days by feeding them with gel food containing 30% of water. Such WR elevated blood osmolality from 310.2±1.2 to 315.6±1.3 mosmol/kg. WR increased vWF mRNA in liver and lung and raised vWF protein in blood. Immunostaining of liver and pancreas revealed increased production of vWF protein by endothelium and increased number of microthrombi inside capillaries. WR also increased blood level of D-dimer, which is fibrinogen degradation product and indicative of thrombogenic state. These results demonstrate that high NaCl increases production of vWF by endothelial cells explaining hypercoagulability and increased risk of thrombosis associated with conditions related to tendency to dehydration and hypernatremia such as aging and diabetes.