钙和钙调素与血管平滑肌细胞的增殖

采用MTT法,一种快速和不用放射物的新方法测定血管平滑肌细胞的增殖。本法与[~3H]TdR参入法和细胞计数法之间均有良好的线性关系。人胚和家兔主动脉平滑肌细胞的增殖依赖于FCS和Ca~(2+)。在FCS存在下,Ca~(2+)可促使细胞进入增殖周期和增加G_1晚期CaM含量;TFP可完全逆转Ca~(2+)的作用;阻断Ca~(2+)内流也能抑制细胞增殖;说明Ca~(2+)-CaM可刺激血管平滑肌细胞增殖,可能通过触发DNA合成所致。

Involvement of Ca~(2+) and calmodulin in the proliferation fo aortic smooth muscle cells

The effect of Ca2+ on the initiation of proliferation of aortic smooth muscle cells (ASMC) is described. In the presence of 10% fetal calf serum, Ca2+stimula ted the growth of cells from human em bryoes and rabbits, their maximal stimulatory concentrations being observed at 506 and 325 μMCa2+,whereas the concomitent increases of the cell growth were 73±31 % and 62±20%, respectively, as compared with low Ca2+ control (29 μM Ca2+). During the 12 h G, period, there was a transient surge of cal modulin (CaM) which doubled the level of soluble CaM at 9 h just before the initiation of DMA synthesis. CaM ourge and the initiation of DNA synthesis were prevented by reducing the . concentration of Ca2+ to 29 μM or by adding 14 μM trifluoperazine. Verapamil also significantly inhibited the cell proliferation depending on the doses.These findings suggest that Ca2+stimulates the cell proliferation, presumably through forming Ca2+-CaM complex, which may stimulate CaM synthesis and eventually lead to DNA synthesis. As proliferation of vascular smooth muscle cells is decisive for the stendsing artery lumen in the course of atherosclerosis and hypertension, Ca2+and CaM may be involved in the pathogenesis of these- diseases.