Increased Extracellular Sodium Concentration as a Factor Regulating Gene Expression in Endothelium

Area of Science:

• Endothelial Cell Biology
• Molecular Physiology
• Biophysics

Background:

• Hyperosmotic stress can induce endothelial cell dysfunction and inflammation.
• Mechanisms involve changes in intracellular sodium/potassium (Na+/K+) ratio, osmolarity, and cell stiffness.
• The role of extracellular Na+ concentration as an independent factor is not fully elucidated.

Purpose of the Study:

• Investigate the effects of short-term hyperosmotic stimulation on endothelial cells.
• Examine changes in mRNA expression of key endothelial genes, including Na+/K+-sensitive ones.
• Assess alterations in the equivalent elasticity constant of human umbilical vein endothelial cell membranes.

Main Methods:

• Human umbilical vein endothelial cells were exposed to hyperosmotic conditions using NaCl or mannitol.
• Intracellular Na+ accumulation and Na,K-ATPase activity were measured.
• mRNA levels of specific genes (IL1α, ATF3, PAR2, PTGS2, NFAT5) were quantified.
• Equivalent elasticity constant of cell membranes was determined.

Main Results:

• NaCl-induced hyperosmotic stimulation, but not mannitol, led to intracellular Na+ accumulation.
• This occurred despite Na,K-ATPase activation and was accompanied by decreased cell membrane elasticity.
• IL1α mRNA decreased with increasing osmolarity, while ATF3, PAR2, and PTGS2 mRNA increased specifically with elevated NaCl.
• NFAT5 expression remained unchanged under experimental conditions.

Conclusions:

• Increased extracellular Na+ concentration is an independent regulator of intracellular Na+/K+ ratio in endothelial cells.
• Elevated extracellular Na+ influences the expression of specific genes (ATF3, PAR2, PTGS2) involved in endothelial function.
• These findings provide insights into the mechanisms of hyperosmotic stress-induced endothelial dysfunction.