ASGSB 1998 Annual Meeting Abstracts

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REGULATION OF THROMBIN RECEPTOR ON SMOOTH MUSCLE CELLS BY MECHANICAL FORCES. K.T. Nguyen¹, M. Papadaki¹, J. Ruef², C. Patterson², M.S. Runge², S.G. Eskin³, and L.V. McIntire¹. ¹Dept. of Bioeng., Rice Univ., Texas, ²Cardiology Division, Univ. Texas Medical Branch, Galveston, and ³Dept. of Cell Biology, Texas Biotechnology Corporation.

The objective of this study is to investigate the effect of mechanical forces such as shear stress and cyclic strain on the expression of protease activated receptor-1(PAR-1) in human aortic smooth muscle cells(HASMC). HASMC were exposed to different levels of shear stress using the parallel plate flow chamber system. Northern blot and flow cytometry analysis indicated that PAR-1 mRNA and protein were downregulated 3 fold by high shear stress, 25 dyn/cm². mRNA half-life studies showed that the decreased mRNA was not due to instability of PAR-1 mRNA. In addition, alterations in HASMC function after exposure to shear stress such as thrombin-induced increase in cytosolic Ca²⁺ and proliferation were examined. Using Fura-2, Ca²⁺ rise after thrombin stimulation in sheared cells was 50% less than in control cells. ³H-thymidine incorporation after thrombin treatment were also reduced in HASMC exposed to shear stress (11931+1473 vs. 15887+677 cpm). In contract to shear stress, PAR-1 mRNA level was upregulated 2 fold by high cyclic strain, 20% strain and 1 Hz. Further studies will be developed to explore the effect of stretch on PAR-1 protein level and alterations in HASMC function. (Supported by NASA-NSCORT: NAG5-4072)

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