MULTIPLE PHENOTYPICALLY DISTINCT SMOOTH-MUSCLE CELL-POPULATIONS EXIST IN THE ADULT AND DEVELOPING BOVINE PULMONARY ARTERIAL MEDIA IN-VIVO
MULTIPLE PHENOTYPICALLY DISTINCT SMOOTH-MUSCLE CELL-POPULATIONS EXIST IN THE ADULT AND DEVELOPING BOVINE PULMONARY ARTERIAL MEDIA IN-VIVO
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DOI：
10.1161/01.res.75.4.669
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发表时间：
1994-10-01
影响因子：
20.1
通讯作者：
STENMARK, KR
中科院分区：
文献类型：
--
作者：
FRID, MG;MOISEEVA, EP;STENMARK, KR
不同的SMC功能可能需要不同的细胞表型。由于主肺动脉具有不同的功能，我们推测它可能含有不同的SMC群体。如果这一假设得到证实，我们希望确定不同群体的发育起源。用特异性抗体分析了胎儿(妊娠60~270天)、新生动物和成年动物主肺动脉中平滑肌收缩和细胞骨架蛋白(Lu-SM-actin、SM myosin、calponin、desmin和Meta-vinculin)的表达。我们证明了在肺动脉壁的结构和细胞成分中存在复杂的、特定部位的异质性。我们发现，基于免疫化学特征、细胞形态和弹性板层排列模式，至少四种细胞/SMC表型在成熟的动脉中膜中同时表达。此外，我们能够评估在发育过程中四个已鉴定的细胞群体中的每一个的表型变化。我们发现，每个细胞都有一定的发育阶段，从而显示出其平滑肌群的特性。然而，每个细胞群体都沿着不同的发育途径前进，这表明存在着多个不同的细胞谱系。在这项研究中描述的一种新的抗Metavinculin抗体在所分析的所有发育阶段可靠地将一个SMC群体与其他SMC群体区分开来。我们的结论是，肺动脉中膜确实是由具有独特谱系的多个表型不同的细胞/SMC群体组成。我们推测，这些不同的细胞群可能在动脉中膜内发挥不同的功能，也可能以独特的方式对病理生理刺激做出反应。
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 (Lu-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 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.