Tonic regulation of vascular permeability.
Tonic regulation of vascular permeability.
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DOI：
10.1111/apha.12076
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Adamson RH
中科院分区：
文献类型：
--
作者：
Curry FR;Adamson RH
我们的主要主题是内皮屏障的分层结构需要由S1P和细胞内cAMP调节的信号通路的持续激活。这些途径调节粘连连接、紧密连接链的连续性，以及糖萼组分的合成和降解的平衡。我们评估了最近的证据，即基线通透性是通过涉及小GTP酶Rap1和rac1的机制的持续活动来维持的。在基础状态下，当小GTP酶的活性因低S1P供应或递送而降低时，屏障就会受到损害。在炎性刺激下，通透性增加可以部分理解为信号减少RAP1和RAC1激活的作用。假设正常和炎症状态下的微血管通透性和选择性都受到持续活跃的机制的调节，因此，当炎症刺激时S1P或细胞内cAMP升高时，它们可以缓冲炎症介质引起的变化，并维持正常的屏障稳定性。当内皮细胞暴露在炎症条件下，随后暴露于升高的S1P或细胞内cAMP时，同样的过程通过首先重建黏附连接，然后调节紧密连接和糖基化来恢复功能屏障。在更极端的炎症条件下，通过RhoA依赖的收缩机制上调RhoA依赖的收缩机制和持续丢失允许炎症细胞进入内皮细胞的表面糖基化来促进更多炎症内皮细胞表型的表达。
Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium.
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影响因子：
4
作者：
Bode, Constantin;Sensken, Sven-Christian;Graeler, Markus H.
通讯作者：
Graeler, Markus H.
影响因子：
5.5
作者：
Colegio, OR;Van Itallie, C;Anderson, JM
通讯作者：
Anderson, JM
影响因子：
5.5
作者：
CLOUGH, G;MICHEL, CC;PHILLIPS, ME
通讯作者：
PHILLIPS, ME
DOI：
10.1152/ajpheart.00937.2007
发表时间：
2008-03-01
影响因子：
4.8
作者：
Adamson, R. H.;Ly, J. C.;Curry, F. E.
通讯作者：
Curry, F. E.
影响因子：
3.8
作者：
Chase, S. D.;Magnani, J. L.;Simon, S. I.
通讯作者：
Simon, S. I.