Cyclical strain increases endothelin-1 secretion and gene expression in human endothelial cells

Area of Science:

• Cardiovascular Biology
• Cellular Physiology
• Endothelial Cell Function

Background:

• Endothelin-1 (Et-1) is a potent vasoconstrictor peptide.
• Endothelial cells play a crucial role in vascular homeostasis.
• The impact of mechanical forces on endothelial Et-1 production is not fully understood.

Purpose of the Study:

• To investigate the effect of cyclical mechanical strain on Et-1 secretion and gene expression in human umbilical vein endothelial cells.
• To elucidate the signaling pathway involved in strain-induced Et-1 modulation.

Main Methods:

• Human umbilical vein endothelial cells cultured on flexible membranes were subjected to controlled cyclical strain (20% strain, 60 cycles/min).
• Et-1 secretion into the culture medium was measured.
• Et-1 mRNA levels were quantified using RT-PCR.
• The role of protein kinase C was assessed using calphostin C inhibition.

Main Results:

• Cyclical strain significantly increased Et-1 secretion (from 0.17 to 0.44 ng/hr/10(6) cells).
• Et-1 mRNA levels showed a time-dependent increase (1.4- to 2.6-fold) with strain, peaking at 6 hours.
• Strain-induced elevation of Et-1 mRNA was completely blocked by calphostin C, indicating protein kinase C pathway involvement.

Conclusions:

• Mechanical strain modulates endothelial Et-1 secretion and gene expression via the protein kinase C pathway.
• Elevated Et-1 under physiological strain may influence vascular and cardiac growth in both normal and pathological conditions.