DENSITY-DEPENDENT ENDOTHELIAL-CELL PRODUCTION OF AN INHIBITOR OF SMOOTH-MUSCLE CELL-GROWTH
DENSITY-DEPENDENT ENDOTHELIAL-CELL PRODUCTION OF AN INHIBITOR OF SMOOTH-MUSCLE CELL-GROWTH
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DOI：
10.1002/jcb.240530104
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发表时间：
1993-09-01
影响因子：
4
通讯作者：
DAMORE, PA
中科院分区：
文献类型：
--
作者：
DODGE, AB;LU, XQ;DAMORE, PA
胚胎数据和超微结构分析表明，原始内皮细胞信号未分化的间充质细胞迁移到形成的血管，随后调节壁细胞的生长和行为。血管成熟后，趋化和有丝分裂信号明显减弱，分化的平滑肌细胞通常保持静止。这种动态平衡似乎在导致以动脉粥样硬化等平滑肌细胞增生为特征的病理的情况下被破坏。通过以不同密度培养内皮细胞，我们试图重建血管发育的不同阶段。稀疏内皮细胞条件培养液刺激血管平滑肌细胞，而密集内皮细胞培养条件培养液则是抑制作用。稀疏血管内皮细胞在融合后内皮细胞培养上清液中培养3天后，可引起剂量依赖性和可逆性的平滑肌细胞抑制。此外，在内皮细胞衍生的抑制物存在的情况下，平滑肌细胞对成纤维细胞生长因子和血小板衍生生长因子等有丝分裂原产生抵抗力。这种抑制活性不是由于具有良好特征的平滑肌细胞生长抑制物、转化生长因子-β型、前列腺素I2或硫酸乙酰肝素蛋白多糖所致。抑制条件介质的部分表征表明，活性分子小于1,000 dA，对煮沸以及对蛋白酶K和肝素酶消化都是稳定的。这些发现支持内皮细胞和平滑肌细胞之间存在细胞间通讯的概念，并为一种新的内皮细胞来源的平滑肌细胞生长抑制物提供证据。(C)1993年Wiley-Liss，Inc.
Embryonic data and ultrastructural analyses suggest that the primitive endothelium signals undifferentiated mesenchymal cells to migrate to the forming blood vessel and subsequently regulates mural cell growth and behavior. Upon maturation of the blood vessel, chemotactic and mitogenic signals are apparently diminished and differentiated smooth muscle cells normally remain quiescent. This homeostasis is seemingly upset in conditions which lead to pathologies characterized by smooth muscle cell hyperplasia such as atherosclerosis. By culturing endothelial cells at different densities, we attempted to re-create the various stages of vascular development. Whereas media conditioned by sparse endothelial cells stimulate smooth muscle cells, media conditioned by dense endothelial cell cultures are inhibitory. Culture of sparse smooth muscle cells in media conditioned for 3 days by postconfluent endothelial cell cultures leads to dose-dependent and reversible smooth muscle cell inhibition. Furthermore, in the presence of the endothelial cell-derived inhibitor, smooth muscle cells are rendered refractory to mitogens such as fibroblast growth factor and platelet-derived growth factor. The inhibitory activity is not attributable to the well-characterized inhibitors of smooth muscle cell growth, transforming growth factor type-beta, prostaglandin I2, or heparan sulfate proteoglycan. Partial characterization of the inhibitory conditioned media suggests that the active molecule is smaller than 1,000 da, and stable to boiling as well as proteinase K and heparinase digestion. These findings support the concept that there is intercellular communication between endothelial cells and smooth muscle cells and provide evidence for a novel endothelial cell-derived smooth muscle cell growth inhibitor. (C) 1993 Wiley-Liss, Inc.