NIH Research Festival
Cardiovascular diseases (CVDs) are a leading health problem. Epidemiologic studies link high salt intake and conditions predisposing to dehydration such as diabetes and old age to increased risk of CVD. Elevation of extracellular sodium is a common consequence of these conditions. Sodium is major electrolyte in plasma and extracellular fluids. Its concentration is maintained within narrow range by osmoregulation. Here, we demonstrate that small elevations of extracellular sodium within or slightly above normal range have adverse cardiovascular consequences. Thus, by PCR array, using human umbilical vein endothelial cells, we analyzed the effect of high NaCl on 84 genes related to endothelial cell biology. The analysis showed that the affected genes regulate many aspects of endothelial cell biology including cell adhesion, proliferation, lymphocyte and leukocyte activation, coagulation, angiogenesis and inflammatory response. In mice, mild water restriction that elevates plasma sodium by only 5 mmol/l increases a key initiator of blood clotting, von Willebrand Factor (vWF), in blood and in vascular endothelium, upregulates mediators of inflammation (VCAM1, E-selectin and MCP-1), promotes atherosclerosis, causes coronary arteries hypertrophy, coronary fibrosis and accelerates aging. In humans, multivariable analysis of data from Atherosclerosis Risk in Community study demonstrated that plasma sodium is positively associated with plasma levels of vWF and cholesterol, with systolic blood pressure and with risks of stroke and coronary heart disease. The findings bring attention to plasma sodium as a possible risk factor for CVDs and give additional support to recommendations for dietary salt restriction and adequate water intake as preventives of CVDs.
Scientific Focus Area: Cell Biology
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