Endothelial cells modulate smooth muscle cell morphology by inhibition of transforming growth factor-beta(1) activation

被引:22
作者
Nackman, GB [1 ]
Bech, FR [1 ]
Fillinger, MF [1 ]
Wagner, RJ [1 ]
Cronenwett, JL [1 ]
机构
[1] DARTMOUTH HITCHCOCK MED CTR,VASC SURG SECT,LEBANON,NH 03756
关键词
D O I
10.1016/S0039-6060(96)80318-7
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. We have previously demonstrated in a coculture model that endothelial cells (ECs) exert regulatory control over smooth muscle cell (SMC) morphology. This study was preformed to test the hypothesis that ECs inhibit transforming growth factor-beta(2) (TGF-beta(1)) activation through the release of plasminogen activator inhibitor (PAI-1). Methods. Bovine SMCs were cultured on a thin, semipermeable membrane, either alone or opposite ECs in coculture (SMC/EC). Conditioned media and cell lysates at 1, 5, and 21 days were assayed for TGF-beta(1) and PAI-1 by enzyme-linked immunoabsorbent assay. Cell proliferation rates, protein, and DNA content were measured and compared with SMC morphology. Results. Activation of TGF-beta(1) was significantly decreased (1.2% versus 18.9% active TGF-beta(1), p < 0.05) and PAI-1 was increased (659 pg/ml versus 343 pg/ml, p < 0.05) in SMC/EC medium on day 1, compared with the medium of SMC alone. Significantly higher levels of PAI-1 were measured in cell lysates of cocultured ECs (128 pg/mu g DNA) than in cocultured SMCs (5.8 pg/mu g DNA, p < 0.05). SMC/EC coculture prevented the SMC hill-and-valley growth morphology seen in SMCs cultured alone. Conclusion. In a model designed to study SMC/EC interactions, it was seen that ECs can alter growth characteristics of SMCs by producing PAI-1, which interferes with the plasminogen pathway of TGF-beta(1) activation. This suggests that reduced EC PAI-1 production could play a role in alternation of SMC phenotype in vivo.
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页码:418 / 426
页数:9
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