Cyclical strain effects on production of vasoactive materials in cultured endothelial cells

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Abstract
Mechanical forces due to fluid flow and cyclical strain can alter endothelial cell morphology and function, including the release of vasoactive materials endothelin, prostacyclin (PGI2), and tissue plasminogen activator (t-PA). In this study, effects of cyclical strain were modeled by culturing bovine aortic endothelial cells on fibronectin-coated elastic membranes of silicone rubber (Silastic®) or poly-etherurethane urea (Mitrathane™). After growing to confluence under static conditions of 37°C in humidified air with 5% CO2, cells were strained cyclically at membrane elongations of 5% or 10% for 24 hours at 1 Hz. Controls were maintained under static conditions or were exposed to fluid motions similar to the strained cells but without stretching. Secretion rates were constant throughout experiments in the strain chamber with no initial burst in metabolism associated with the initiation of strain. Secretion rates were not altered by choice of elastic membrane. At a physiological level of 10% cyclical strain, prostacyclin and endothelian secretion rates were increased by 2.5-fold and 1.7-fold, respectively, above stationary controls. Endothelin production demonstrated a dose-dependent response with cyclical strain, while PGI2 appeared to require a threshold strain before an increase in secretion occurred. No significant differences in t-PA levels were seen in cyclically strained cells compared with controls. These results indicate that endothelial cells respond metabolically to cyclical strain and suggest that mechanical strain may modulate secretion of selective vasoactive materials by vascular endothelial cells.