Effects of cyclical strain on the production of vasoactive materials by cultured human and bovine endothelial cells
Carosi, Joseph Antonio
Doctor of Philosophy
Much recent emphasis in vascular biology has focused on endothelial cells which form the inner lining of blood vessels. This unique arterial location exposes these cells directly to mechanical forces resulting from blood flow and the transmission of the pressure wave through a compliant vessel. In this study, the effects of the cyclical expansion and relaxation of the vessel wall on endothelial cell metabolism have been modeled using a uniaxial strain device. A normal range of physiological strains for large arteries was examined. The production rates of prostacyclin (PGI$\sb2$), endothelin, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-type 1 (PAI-1) by endothelial cells were constant over 24 hour periods. The production of both PGI$\sb2$ and endothelin was enhanced by cells exposed to a high level of cyclical strain compared to controls, while t-PA production was unaltered. These results were true for human and bovine endothelial cells. The stimulation of endothelin production was dose dependent with the level of strain while PGI$\sb2$ stimulation required a minimal level of strain before increases over controls were observed. Human endothelial cells subjected to cyclical strain showed elevated production of PAI-1 compared to controls. The possibility that cyclical strain could be used to regulate cell function was investigated. Cyclical strain was applied in an on-off-on manner over a 36 hour period with a 12 hour division between initial application of strain and final reapplication of strain. When the strain was stopped, PGI$\sb2$ production rapidly returned to control levels while endothelin production remained elevated but at a level significantly below the initially stimulated rate. Reapplication of cyclical strain caused a return of the endothelin production rate to a level essentially the same as that during the initial stimulation period. This study initiated a quantitative investigation of cyclical strain effects on endothelial cell production of the mRNA levels of prostaglandin H (PGH) synthase gene, the enzyme of which is involved in production of PGI$\sb2$. Preliminary results using a quantitative reverse transcription-polymerase chain reaction technique suggested that mRNA levels of PGH synthase are not altered in response to cyclical strain.