Cerebral microvascular endothelial cell tube formation: role of astrocytic epoxyeicosatrienoic acid release
Cerebral microvascular endothelial cell tube formation: role of astrocytic epoxyeicosatrienoic acid release
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DOI：
10.1152/ajpheart.2000.278.4.h1163
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发表时间：
2000-04-01
影响因子：
4.8
通讯作者：
Harder, DR
中科院分区：
文献类型：
--
作者：
Munzenmaier, DH;Harder, DR
脑微血管内皮细胞 (CMVEC) 与星形胶质细胞 (AS) 共培养时形成管。因此，AS 似乎对于介导大脑血管生成很重要。我们假设 AS 通过释放可溶性因子来调节 CMVEC 管的形成。当与 50% 条件 AS 培养基一起孵育 24 小时时，培养的 CMVEC 中的胸苷掺入增加了 305% [对照：每孔每分钟 (cpm) 52,755 +/- 4,838 计数，条件 161,082 +/- 12,099 cpm/孔，n = 8]。因为我们的实验室之前已经表明 AS 可以产生环氧二十碳三烯酸 (EET)，这是已知的有丝分裂原，所以我们研究了 AS 释放的 EET 是否是 CMVEC-AS 共培养物中管形成的原因。将 AS 接种到 Lab-Tek 载玻片上，第二天将 CMVEC 接种到 AS 上，并在使用和不使用 17-十八氰酸 (17-ODYA) 阻断细胞色素 P-450 环氧化酶的情况下再培养 5 天。与对照相比（93.8%），接受 17-ODYA 的共培养物中的管形成受到显着抑制。这些数据表明管的形成需要 AS 释放 EET。
Cerebral microvascular endothelial cells (CMVEC) form tubes when cocultured with astrocytes (AS). Therefore, it appears that AS may be important in mediating angiogenesis in the brain. We hypothesized that AS modulate CMVEC tube formation by releasing a soluble factor. Thymidine incorporation in cultured CMVEC increased 305% when incubated with 50% conditioned AS medium for 24 h [control: 52,755 +/- 4,838 counts per minute (cpm) per well, conditioned 161,082 +/- 12,099 cpm/well, n = 8]. Because our laboratory has previously shown that AS can produce epoxyeicosatrienoic acids (EETs), which are known mitogens, we investigated whether release of EETs by AS is responsible for tube formation in the CMVEC-AS coculture. AS were seeded on Lab-Tek slides, CMVEC were seeded on the AS the next day, and cultures were allowed to progress for another 5 days with and without cytochrome P-450 epoxygenase blockade by 17-octadecynoic acid (17-ODYA). Tube formation in cocultures receiving 17-ODYA was significantly inhibited compared with control (93.8%). These data suggest that tube formation requires the release of EETs by AS.