Communication Is Key: Mechanisms of Intercellular Signaling in Vasodilation.
Communication Is Key: Mechanisms of Intercellular Signaling in Vasodilation.
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DOI：
10.1097/fjc.0000000000000463
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发表时间：
2017-05
影响因子：
3
通讯作者：
Gutterman DD
中科院分区：
文献类型：
--
作者：
Freed JK;Gutterman DD
30年前，罗伯特·F·福尔奇戈特得出结论，一氧化氮--一种传统上被认为是燃油废气中有毒成分的化合物--实际上是从内皮细胞释放出来的，并以旁分泌的方式诱导潜在的血管平滑肌松弛，导致血管扩张。这一发现为更彻底地了解血管细胞间和细胞内通讯铺平了道路，这种通讯支持调节区域灌流的过程，以匹配局部组织的氧气需求。血管调节不仅受血管内皮细胞释放多种血管活性物质如一氧化氮、花生四烯酸代谢产物和活性氧的控制，还受血管壁上的物理作用力和缝隙连接的电子紧张性传导的控制。虽然内皮细胞是血管活性物质的重要来源，但旁分泌介质也可以从血管周围脂肪、心肌和动脉外膜细胞等周围实质中释放出来，发挥局部或远程的血管舒缩作用。这篇综述的重点将突出细胞间通讯有助于血管扩张机制的各种方式。将回顾旁分泌信号和实质影响，以及通过缝隙连接、连接蛋白和肌内皮反馈的区域血管通讯。还将讨论更新的通信模式，如水泡和microRNA信号。
Thirty years ago Robert F. Furchgott concluded that nitric oxide, a compound traditionally known to be a toxic component of fuel exhaust, is in fact released from the endothelium, and in a paracrine fashion, induces relaxation of underlying vascular smooth muscle resulting in vasodilation. This discovery has helped pave the way for a more thorough understanding of vascular inter- and intracellular communication that supports the process of regulating regional perfusion to match local tissue oxygen demand. Vasoregulation is not only controlled by endothelial release of a diverse class of vasoactive compounds such as nitric oxide, arachidonic acid metabolites, and reactive oxygen species, but also via physical forces on the vascular wall and through electrotonic conduction through gap junctions. Although the endothelium is a critical source of vasoactive compounds, paracrine mediators can also be released from surrounding parenchyma such as perivascular fat, myocardium, and cells in the arterial adventitia to exert either local or remote vasomotor effects. The focus of this review will highlight the various means by which intercellular communication contributes to mechanisms of vasodilation. Paracrine signaling and parenchymal influences will be reviewed as well as regional vessel communication via gap junctions, connexons, and myoendothelial feedback. More recent modes of communication such as vesicular and microRNA signaling will also be discussed.