Effect of probucol on smooth muscle cell proliferation and dedifferentiation after vascular injury in rabbits: Possible role of PDGF
Effect of probucol on smooth muscle cell proliferation and dedifferentiation after vascular injury in rabbits: Possible role of PDGF
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DOI：
10.1023/a:1007761631674
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发表时间：
1998-07-01
影响因子：
3.4
通讯作者：
Yamaguchi, H
中科院分区：
文献类型：
--
作者：
Miyauchi, K;Aikawa, M;Yamaguchi, H
我们之前曾报道过普罗布考降低再狭窄率的临床研究。这种效应的机制尚不清楚。再狭窄的特征是血管内皮细胞(SMC)增殖引起的新生内膜增生，增加了血小板衍生生长因子(PDGF)-A和SMemb的表达。SMemb是一种主要在胚胎平滑肌中表达的非肌型肌球蛋白重链，可作为去分化SMC的分子标志物。本研究旨在分析普罗布考对兔球囊损伤后新生内膜增殖及PDGF-A和SMemb表达水平的影响。普罗布考从颈动脉球囊损伤前2周至致死时(球囊损伤后2周或4周)口服1.3g/d。用计算机形态计量学程序测定血管内膜面积。计数α-肌动蛋白阳性细胞和增殖细胞核抗原标记细胞，定量检测SMC增殖情况。用核糖核酸酶保护法分析PDGF-A和SMemb基因的表达。用免疫组织化学方法检测SMemb的表达。普罗布考使内膜面积减少70%，内膜内SMC和增殖细胞核抗原标记细胞数减少。未处理组球囊损伤后PDGF-AmRNA表达显著增加，而普罗布考治疗后PDGF-AmRNA表达明显抑制。损伤动脉中SMemb的表达在mRNA和蛋白水平均显著升高。但普罗布考不能抑制SMemb的表达。普罗布考能有效抑制SMC增殖，其机制可能与抑制PDGF的表达有关。
We previously reported a clinical study in which probucol reduced the restenosis rate. The mechanism of this effect is unclear. Restenosis is characterized by neointimal hyperplasia caused by proliferation of smooth muscle cells (SMCs), which increases the expression of Platelet-derived growth factor (PDGF)-A and SMemb. SMemb, a non-muscle-type myosin heavy chain most predominantly expressed in embryonic smooth muscle, can be used as a good molecular marker for dedifferentiated SMC. The aim of this study was to analyze the effect of probucol on neointimal proliferation and the level of expression of PDGF-A and SMemb after balloon injury in rabbits. Probucol was given orally 1.3 g/d from 2 weeks prior to carotid balloon injury to the time of killing (2 or 4 weeks after balloon injury). Intimal area was determined histologically using a computerized morphometry program. For quantification of SMC proliferation, alpha-actin-positive cells and proliferating cell nuclear antigen (PCNA)-labeled cells were counted. The expression of PDGF-A and SMemb mRNA was analyzed by the RNase protection assay. SMemb expression was also examined by immunohistochemistry. Probucol remarkably decreased intimal area by 70% and the number of SMC and PCNA-labeled cells in the intima. The expression of PDGF-A mRNA was significantly increased after balloon injury in untreated rabbits, whereas it was markedly suppressed with probucol treatment. The expression of SMemb was significantly increased in injured arteries at mRNA and protein levels. However, probucol did not suppress SMemb expression. Probucol is effective in preventing SMC proliferation, which is possibly due to a decrease in the expression of PDGF.