Effects of Elevated Downstream Pressure and the Role of Smooth Muscle Cell Coupling through Connexin45 on Lymphatic Pacemaking.
Effects of Elevated Downstream Pressure and the Role of Smooth Muscle Cell Coupling through Connexin45 on Lymphatic Pacemaking.
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DOI：
10.3390/biom10101424
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发表时间：
2020-10-08
期刊：
影响因子：
5.5
通讯作者：
Davis MJ
中科院分区：
文献类型：
--
作者：
Castorena-Gonzalez JA;Li M;Davis MJ
淋巴管依赖于自发的淋巴肌细胞（LMC）收缩和单向管腔内瓣膜来有效地泵送淋巴液并将其返回到血流中。已知管腔内压力调节血管的收缩功能，压力升高导致收缩频率增加和幅度降低。收缩通常由主导起搏器启动，并在强耦合LMC之间高度夹带。以前，我们发现连接蛋白45是介导LMC-LMC电耦合的主要连接蛋白亚型。来自缺乏平滑肌连接蛋白45的小鼠的淋巴管显示不协调、受损的收缩。在这里，我们利用这个connexin 45缺陷模型，压力肌造影，最近开发的新的分析工具，以评估下游压力升高的淋巴起搏器的数量，位置和频率的影响。我们的研究结果表明，在健康对照组的血管中，下游压力的增加导致新起搏器的招募/发展和收缩频率的增加，同时继续观察到主导起搏器。相比之下，connexin 45缺陷小鼠的血管显示出明显更多的起搏器，但没有一个是占主导地位的;这随着下游压力的升高而恶化。这些结果表明了一种潜在的保护机制，通过这种机制，淋巴管系统适应下游压力的瞬时增加，但在慢性下游压力升高的情况下可能无法持续。
Lymphatic vessels rely on spontaneous lymphatic muscle cell (LMC) contractions and one-way intraluminal valves to efficiently pump lymph and return it into the bloodstream. Intraluminal pressure is known to regulate the contractile function of lymphatics, with pressure elevation leading to increased contraction frequency and decreased amplitude. Contractions are normally initiated by a dominant pacemaker and are highly entrained among strongly coupled LMCs. Previously, we found that connexin45 is the major connexin isoform mediating LMC-LMC electrical coupling. Lymphatics from mice lacking smooth muscle connexin45 display uncoordinated, impaired contractions. Here, we utilized this connexin45-deficient model, pressure myography, and recently developed, novel analytical tools to assess the effects of elevated downstream pressure on the number, location, and frequency of lymphatic pacemakers. Our results show that, in vessels from healthy controls, an increase in downstream pressure resulted in the recruitment/development of new pacemakers and increased contractile frequency while a dominant pacemaker continued to be observed. In contrast, vessels from connexin45-deficient mice displayed significantly more pacemakers, but none were dominant; this worsened with elevated downstream pressure. These results suggest a potential protective mechanism through which the lymphatic vasculature adapts to transient increases in downstream pressure, but which may not be sustained in scenarios with chronic elevated downstream pressure.
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影响因子：
3.4
作者：
Hald, Bjorn Olav;Castorena-Gonzalez, Jorge Augusto;Davis, Michael John
通讯作者：
Davis, Michael John
影响因子：
1.4
作者：
Davis, Michael J.;Zawieja, David C.;Gashev, Anatoliy A.
通讯作者：
Gashev, Anatoliy A.
影响因子：
1.4
作者：
Gasheva, Olga Yu;Trzeciakowski, Jerome P.;Zawieja, David C.
通讯作者：
Zawieja, David C.
影响因子：
--
作者：
OLSZEWSKI, WL;ENGESET, A
通讯作者：
ENGESET, A
DOI：
10.1111/j.1748-1716.1977.tb10364.x
发表时间：
1977-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
ENGESET, A;OLSZEWSKI, W;THEODORSEN, L
通讯作者：
THEODORSEN, L