α-smooth-muscle actin and microvascular precursor smooth-muscle cells in pulmonary hypertension

α-smooth-muscle actin and microvascular precursor smooth-muscle cells in pulmonary hypertension
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DOI:
10.1165/ajrcmb.20.4.3357
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发表时间:
1999-04-01
影响因子:
6.4
通讯作者:
Steudel, W
Steudel, W
中科院分区:
医学1区
文献类型:
--
作者:
Jones, R;Jacobson, M;Steudel, W

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对于肺动脉高压(PH)中成人肺微血管平滑肌细胞发育的分子基础知之甚少。利用定量和免疫金电子显微镜技术,我们报告了表达α-平滑肌肌动蛋白的微血管前体平滑肌细胞(PSMCs)的发育α-SMA是平滑肌细胞分化的第一个标志物,在高氧PH大鼠中。具有α SMA细胞的(肺泡壁)血管的增加先于(P-chi 2 < 0.02,第4天)近端(肺泡管)血管的增加(P-chi 2 < < 0.02,第14天)。具有表达α SMA的细胞的最小血管(直径< 50 μ m)随时间增加最多(P-chi 2 < 0.001)。免疫阳性的PSMCs在正常肺中很少,而在高氧中常见。在高氧早期(第4天),在中间细胞中检测到用α SMA修饰的发育良好的细丝阵列。随后在募集至血管壁的成纤维细胞中检测到类似的细丝网络(第7天至第14天)。到第28天,来源于成纤维细胞的细胞在血管壁中形成了几层,并在中心域或网格中表达了致密的α SMA细丝阵列。因此,中间细胞是高氧肺动脉高压中微血管早期表达α SMA的细胞的来源,而在晚期-微血管强烈新生肌化的时间-细胞的成纤维细胞的来源。
Little is known of the molecular basis of smooth-muscle cell development in the microvessels of the adult lung in pulmonary hypertension (PH). Using quantitative and immunogold electron microscopy techniques we report the development of microvascular precursor smooth-muscle cells (PSMCs) expressing alpha-smooth-muscle actin (alpha SMA), a first marker of smooth-muscle cell differentiation, in rats with hyperoxic PH. Increase in the frequency of distal (alveolar wall) vessels with alpha SMA cells preceded (P-chi 2 < 0.02, Day 4) the increase in proximal (alveolar duct) vessels (P-chi 2 < < 0.02, Day 14). The smallest vessel with cells expressing alpha SMA (< 50 mu m in diameter) increased most with time (P-chi 2 < 0.001). Immunopositive PSMCs were rare in normal lung and frequent in hyperoxia, Well-developed filament arrays decorated with alpha SMA were detected in intermediate cells early in hyperoxia (Day 4). Similar filament networks were detected later in fibroblasts recruited to vessel walls (Days 7 to 14). By Day 28, cells derived from fibroblasts formed several layers in the vessel wall and expressed dense alpha SMA filament arrays, in either a central domain or mesh. Thus, intermediate cells are the source of cells expressing alpha SMA early in the microvessels in hyperoxic pulmonary hypertension and fibroblasts of cells in the late stage-the time of intense neomuscularization of the microvessels.