Lyall F, Deehan M R, Greer I A, Boswell F, Brown W C, McInnes G T
Department of Obstetrics and Gynaecology, University of Glasgow, Royal Infirmary, UK.
J Hypertens. 1994 Oct;12(10):1139-45.
To determine whether changes in haemodynamic load, simulated in vitro by mechanically stretching cultured vascular smooth muscle cells, could be transduced into biochemical signals similar to those produced by growth factors.
A system was developed which was capable of stretching cultured vascular smooth muscle cells from 0 to 20%. The effect of stretching quiescent vascular smooth muscle cells on both c-fos messenger RNA (mRNA) expression and release of total inositol phosphates was determined over a time interval of 0-360 min.
Rat mesenteric artery vascular smooth muscle cells were grown using standard cell culture methods. Induction of the proto-oncogene, c-fos, was determined by Northern blotting. Phosphoinositide breakdown was assessed by measuring [3H]-inositol phosphates released from prelabelled cells.
A 20% fixed stretch resulted in a rapid induction of c-fos mRNA which reached maximal levels by 15 min. The amount of c-fos mRNA detected was dependent on the degree of stretch, with maximum induction obtained for 15 and 20% stretch. The effects of mechanical stretch were also assessed on phosphoinositide turnover by measuring [3H]-inositol phosphates released from prelabelled cells. A 20% fixed stretch of vascular smooth muscle cells for 20 min resulted in a 3.2-fold increase in total [3H]-inositol phosphates released compared with unstretched cells.
Our results show that mechanical stretch increases proto-oncogene expression and phosphoinositide turnover in vascular smooth muscle cells in vitro. These observations suggest that mechanical stretch and growth factors share common signal transduction pathways which may be important in the development of vascular hypertrophy.
通过机械拉伸培养的血管平滑肌细胞在体外模拟血流动力学负荷变化，确定其是否能转化为与生长因子产生的信号类似的生化信号。
开发了一种能够将培养的血管平滑肌细胞拉伸0%至20%的系统。在0 - 360分钟的时间间隔内，测定拉伸静止血管平滑肌细胞对c-fos信使核糖核酸（mRNA）表达和总肌醇磷酸释放的影响。
采用标准细胞培养方法培养大鼠肠系膜动脉血管平滑肌细胞。通过Northern印迹法测定原癌基因c-fos的诱导情况。通过测量从预先标记的细胞中释放的[3H] - 肌醇磷酸来评估磷酸肌醇的分解。
20%的固定拉伸导致c-fos mRNA迅速诱导，在15分钟时达到最高水平。检测到的c-fos mRNA量取决于拉伸程度，在15%和20%拉伸时诱导程度最大。还通过测量从预先标记的细胞中释放的[3H] - 肌醇磷酸来评估机械拉伸对磷酸肌醇周转的影响。与未拉伸的细胞相比，将血管平滑肌细胞固定拉伸20%持续20分钟导致释放的总[3H] - 肌醇磷酸增加3.2倍。
我们的结果表明，机械拉伸可增加体外血管平滑肌细胞中原癌基因的表达和磷酸肌醇的周转。这些观察结果表明，机械拉伸和生长因子共享共同的信号转导途径，这可能在血管肥大的发展中起重要作用。
