Frid M G, Moiseeva E P, Stenmark K R
Developmental Lung Biology Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Circ Res. 1994 Oct;75(4):669-81. doi: 10.1161/01.res.75.4.669.
Different smooth muscle cell (SMC) functions may require different cell phenotypes. Because the main pulmonary artery performs diverse functions, we hypothesized that it would contain heterogeneous SMC populations. If the hypothesis were confirmed, we wished to determine the developmental origin of the different populations. Using specific antibodies, we analyzed the expression of smooth muscle (SM) contractile and cytoskeletal proteins (alpha-SM-actin, SM myosin, calponin, desmin, and meta-vinculin) in the main pulmonary artery of fetal (60 to 270 days of gestation), neonatal, and adult animals. We demonstrated the existence of a complex, site-specific heterogeneity in the structure and cellular composition of the pulmonary arterial wall. We found that at least four cell/SMC phenotypes, based on immunobiochemical characteristics, cell morphology, and elastic lamellae arrangement pattern, were simultaneously expressed within the mature arterial media. Further, we were able to assess phenotypic alterations in each of the four identified cell populations during development. We found that each cell population within the arterial media expressed alpha-SM-actin at least at certain stages of development, thus demonstrating its smooth muscle identity. However, each cell population progressed along different developmental pathways, suggesting the existence of multiple and distinct cell lineages. A novel anti-metavinculin antibody described in this study reliably distinguished one SMC population from the others during all the developmental stages analyzed. We conclude that the pulmonary arterial media is indeed composed of multiple phenotypically distinct cell/SMC populations with unique lineages. We speculate that these distinct cell populations may serve different functions within the arterial media and may also respond in unique ways to pathophysiological stimuli.
不同的平滑肌细胞（SMC）功能可能需要不同的细胞表型。由于主肺动脉执行多种功能，我们推测它会包含异质性的SMC群体。如果该假设得到证实，我们希望确定不同群体的发育起源。我们使用特异性抗体，分析了胎儿（妊娠60至270天）、新生儿和成年动物主肺动脉中平滑肌（SM）收缩蛋白和细胞骨架蛋白（α-SM-肌动蛋白、SM肌球蛋白、钙调蛋白、结蛋白和间位纽蛋白）的表达。我们证明了肺动脉壁的结构和细胞组成中存在复杂的、位点特异性的异质性。我们发现，基于免疫生化特征、细胞形态和弹性板排列模式，在成熟动脉中膜内同时表达至少四种细胞/SMC表型。此外，我们能够评估在发育过程中四个已鉴定细胞群体中每个群体的表型变化。我们发现动脉中膜内的每个细胞群体至少在发育的某些阶段表达α-SM-肌动蛋白，从而证明其平滑肌特性。然而，每个细胞群体沿着不同的发育途径发展，这表明存在多个不同的细胞谱系。本研究中描述的一种新型抗间位纽蛋白抗体在所有分析的发育阶段都能可靠地将一个SMC群体与其他群体区分开来。我们得出结论，肺动脉中膜确实由多个具有独特谱系的表型不同的细胞/SMC群体组成。我们推测这些不同的细胞群体可能在动脉中膜内发挥不同的功能，并且也可能以独特的方式对病理生理刺激作出反应。
