Uehara Y, Ishimitsu T, Kimura K, Ishii M, Ikeda T, Sugimoto T
2nd Department of Medicine, University of Tokyo, Japan.
Prostaglandins. 1988 Dec;36(6):847-57. doi: 10.1016/0090-6980(88)90061-5.
To define the roles of eicosanoids in vascular smooth muscle cells (VSMC) growth, we examined the effects of exogenous eicosanoids on (3H)thymidine uptake by cultured VSMC of Wistar rats. Stable prostacyclin (PGI2) analog, OP-41483, significantly decreased the incorporation of (3H)thymidine into deoxyribonucleic acid (DNA) of VSMC in a dose dependent manner from 10(-8) to 10(-4) M. Prostaglandin E2 (PGE2) and PGD2 ranging from 10(-8) to 10(-4) M also dose-dependently decreased the (3H)thymidine uptake by VSMC. In contrast, stable thromboxane A2 analog, STA2, significantly increased the incorporation of (3H)thymidine into DNA in a dose dependent manner from 10(-8) to 10(-4) M. The dose response curve of STA2 was shifted toward a lowered response when 10(-5) M PGI2 analog, PGE2 or PGD2 was added in the culture medium. Thus, it is indicated that vasodepressor eicosanoids decrease the proliferation of VSMC, whereas vasoconstrictor TXA2 enhances the VSMC growth. Vascular smooth muscle cells possibly autoregulate the cell proliferation through the eicosanoids generation.
为了确定类花生酸在血管平滑肌细胞(VSMC)生长中的作用,我们研究了外源性类花生酸对Wistar大鼠培养的VSMC摄取(3H)胸腺嘧啶核苷的影响。稳定的前列环素(PGI2)类似物OP - 41483以剂量依赖方式(10^(-8)至10^(-4) M)显著降低(3H)胸腺嘧啶核苷掺入VSMC的脱氧核糖核酸(DNA)中。前列腺素E2(PGE2)和前列腺素D2(PGD2)在10^(-8)至10^(-4) M范围内也呈剂量依赖性降低VSMC对(3H)胸腺嘧啶核苷的摄取。相反,稳定的血栓素A2类似物STA2以剂量依赖方式(10^(-8)至10^(-4) M)显著增加(3H)胸腺嘧啶核苷掺入DNA中。当在培养基中加入10^(-5) M的PGI2类似物、PGE2或PGD2时,STA2的剂量反应曲线向较低反应方向移动。因此,表明血管舒张类花生酸可降低VSMC的增殖,而血管收缩剂血栓素A2可增强VSMC生长。血管平滑肌细胞可能通过类花生酸生成自动调节细胞增殖。