Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties.
Phosphodiesterase inhibitor modulation of brain microvascular endothelial cell barrier properties.
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DOI：
10.1016/j.jns.2012.06.005
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发表时间：
2012-09-15
影响因子：
4.4
通讯作者：
Fisher, Mark J.
中科院分区：
文献类型：
--
作者：
Liu, Shuo;Yu, Chuanhui;Yang, Fan;Paganini-Hill, Annlia;Fisher, Mark J.
Brain microvascular disorders, including cerebral microscopic hemorrhage, have high prevalence but few treatment options. To develop new strategies for these disorders, we analyzed effects of several phosphodiesterase (PDE) inhibitors on human brain microvascular endothelial cells (HBEC). We modified barrier properties and response to histamine of HBEC using cilostazol (PDE-3 inhibitor), rolipram (PDE-4 inhibitor), and dipyridamole (non-specific PDE inhibitor). Cilostazol and dipyridamole altered distribution of endothelial F-actin. Cilostazol increased expression of tight junction protein claudin-5 by 118 % compared to control (p<.001). Permeability to albumin was decreased by cilostazol (21% vs control, p<.05), and permeability to dextran (70Kd) was decreased by both cilostazol (37% vs control, p<.001) and dipyridamole (44% vs control, p<.0001). Cilostazol increased trans-endothelial electrical resistance (TEER) after 12 hours by 111% compared to control (p<.0001). Protein kinase A (PKA) inhibitors H89 and KT5720 attenuated the TEER increase by cilostazol. Transient increased permeability in response to histamine was significantly mitigated by cilostazol, but not other PDE inhibitors. These findings demonstrate distinctive effects of cilostazol and other PDE inhibitors on HBEC, including enhanced barrier characteristics and mitigation of response to histamine. PKA-mediated effects of cilostazol were prominent in this model. These in vitro findings are consistent with therapeutic potential of PDE inhibitors in human brain microvascular disorders.
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DOI：
10.1074/jbc.m110.203604
发表时间：
2011-04-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Blackman BE;Horner K;Heidmann J;Wang D;Richter W;Rich TC;Conti M
通讯作者：
Conti M
影响因子：
5.3
作者：
Fukuhara, S;Sakurai, A;Mochizuki, N
通讯作者：
Mochizuki, N
影响因子：
2.1
作者：
Ishiguro, Mitsunori;Suzuki, Yukiya;Hara, Hideaki
通讯作者：
Hara, Hideaki
影响因子：
5
作者：
Birk, S;Edvinsson, L;Kruuse, C
通讯作者：
Kruuse, C
影响因子：
3.9
作者：
Cooper, DMF
通讯作者：
Cooper, DMF