Absence of venous valves in mice lacking Connexin37.
Absence of venous valves in mice lacking Connexin37.
复制标题
DOI：
10.1016/j.ydbio.2012.10.032
复制
发表时间：
2013-01-15
影响因子：
2.7
通讯作者：
Simon, Alexander M.
中科院分区：
文献类型：
--
作者：
Munger, Stephanie J.;Kanady, John D.;Simon, Alexander M.
静脉瓣膜在血液循环中起着至关重要的作用，促进血液从浅静脉和深静脉向心脏的单向运动。通过防止逆行流动，静脉瓣使毛细血管和小静脉免受压力升高的损害，特别是在骨骼肌收缩期间。在病理上，瓣膜功能不全或瓣膜缺失是慢性静脉功能不全和静脉曲张等静脉疾病的常见特征。这些疾病的根本原因尚不清楚，但先天性静脉瓣发育不全或不发育可能在某些情况下起作用。尽管在心脏和淋巴瓣膜形态发生的研究中取得了进展，但控制静脉瓣膜发育和维持的分子机制仍然知之甚少。在这里，我们表明，在小鼠的带瓣静脉，三个间隙连接蛋白（连接蛋白，Cxs），Cx37，Cx43和Cx47，是专门在一个高度极化的方式表达的阀门，与Cx43的上游侧的瓣叶和Cx37的下游侧。令人惊讶的是，Cx43的表达强烈诱导的非瓣膜静脉内皮浅静脉后，上覆的皮肤受伤。此外，我们发现，在Cx37缺陷的小鼠，静脉瓣膜是完全缺席。因此，Cx37是一种参与细胞间通讯的蛋白质，是迄今为止发现的对静脉瓣的发育或维持至关重要的少数蛋白质之一。由于Cx对于淋巴管中瓣膜的发育也是必要的，因此我们的结果支持了控制静脉和淋巴管中瓣膜发育的共同分子途径的概念。
Venous valves play a crucial role in blood circulation, promoting the one-way movement of blood from superficial and deep veins towards the heart. By preventing retrograde flow, venous valves spare capillaries and venules from being subjected to damaging elevations in pressure, especially during skeletal muscle contraction. Pathologically, valvular incompetence or absence of valves are common features of venous disorders such as chronic venous insufficiency and varicose veins. The underlying causes of these conditions are not well understood, but congenital venous valve aplasia or agenesis may play a role in some cases. Despite progress in the study of cardiac and lymphatic valve morphogenesis, the molecular mechanisms controlling the development and maintenance of venous valves remain poorly understood. Here, we show that in valved veins of the mouse, three gap junction proteins (Connexins, Cxs), Cx37, Cx43, and Cx47, are expressed exclusively in the valves in a highly polarized fashion, with Cx43 on the upstream side of the valve leaflet and Cx37 on the downstream side. Surprisingly, Cx43 expression is strongly induced in the non-valve venous endothelium in superficial veins following wounding of the overlying skin. Moreover, we show that in Cx37-deficient mice, venous valves are entirely absent. Thus, Cx37, a protein involved in cell-cell communication, is one of only a few proteins identified so far as critical for the development or maintenance of venous valves. Because Cxs are necessary for the development of valves in lymphatic vessels as well, our results support the notion of common molecular pathways controlling valve development in veins and lymphatic vessels.
登录
查看更多内容
影响因子：
11.8
作者：
Bazigou, Eleni;Xie, Sherry;Chen, Chun;Weston, Anne;Miura, Naoyuki;Sorokin, Lydia;Adams, Ralf;Muro, Andres F.;Sheppard, Dean;Makinen, Taija
通讯作者：
Makinen, Taija
DOI：
10.1186/1478-811x-7-4
发表时间：
2009-03-12
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Dbouk HA;Mroue RM;El-Sabban ME;Talhouk RS
通讯作者：
Talhouk RS
影响因子：
15.9
作者：
Bazigou, Eleni;Lyons, Oliver T. A.;Makinen, Taija
通讯作者：
Makinen, Taija
DOI：
10.1152/ajpheart.00683.2011
发表时间：
2011-11-01
影响因子：
4.8
作者：
Fang, Jennifer S.;Angelov, Stoyan N.;Burt, Janis M.
通讯作者：
Burt, Janis M.
影响因子：
--
作者：
Kampmeier, OF;Birch, CLF
通讯作者：
Birch, CLF