Differential Endothelial Gap Junction Expression in Venous Vessels Exposed to Different Hemodynamics

Chang, Chi-Jen; Wu, Lung‐Sheng; Hsu, Lung‐An; Chang, Gwo‐Jyh; Chen, Chin-Fen; Yeh, Hung‐I; Ko, Yousang

doi:10.1369/jhc.2010.956425

Cited by 12 publications

(11 citation statements)

References 29 publications

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“…In capillaries, the primary exchange vessels within the body, Cx37 and Cx43 are typically present between ECs. Finally, Cx43 and Cx37 have been identified in ECs of (non-valved) veins (19). Interestingly, ECs on venous valves show a particular Cx expression pattern with Cx43 at upstream sides, Cx37 at downstream sides and Cx47 being restricted to a specific subset of cells composing the valves (20,21).…”

Section: Figurementioning

confidence: 99%

Endothelial connexins in vascular function

2019

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Gap junctions are essential for intercellular crosstalk in blood and lymphatic vasculature. These clusters of intercellular channels ensure direct communication among endothelial cells and between endothelial and smooth muscle cells, and the synchronization of their behavior along the vascular tree. Gap junction channels are formed by connexins; six connexins form a connexon or hemichannel and the docking of two connexons result in a full gap junction channel allowing for the exchange of ions and small metabolites between neighboring cells. Recent evidence indicates that the intracellular domains of connexins may also function as an interaction platform (interactome) for other proteins, thereby regulating their function. Interestingly, fragments of Cx proteins generated by alternative internal translation were recently described, although their functions in the vascular wall remain to be uncovered. Variations in connexin expression are observed along different types of blood and lymphatic vessels; the most commonly found endothelial connexins are Cx37, Cx40, Cx43 and Cx47. Physiological studies on connexin-knockout mice demonstrated the essential roles of these channel-forming proteins in the coordination of vasomotor activity, endothelial permeability and inflammation, angiogenesis and in the maintenance of fluid balance in the body.

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Section: Figurementioning

confidence: 99%

Endothelial connexins in vascular function

2019

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“…Although a few studies have documented connexin (Cx) proteins in veins that lack valves (Chang et al, 2010; Inai and Shibata, 2009; Shiojiri et al, 2006), the expression and function of Cxs in venous valves has not yet been examined. Comprising a family of 21 members in humans, Cxs assemble into gap junction intercellular channels that allow for the direct diffusional transfer of small molecules, including active signaling agents, between adjacent cells (Goodenough and Paul, 2009).…”

Section: Introductionmentioning

confidence: 99%

Absence of venous valves in mice lacking Connexin37

Munger

Kanady

Simon

2013

Developmental Biology

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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.

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“…The influence of flow on endothelial Cx expression both in vivo and in vitro has been most intensively investigated for Cx43 (8,14,24,28), whereas fewer data have been published concerning Cx40 (6,18,25). The latter show agreement about endothelial Cx40 expression being induced by shear stress in repeatedly divided EC cultures.…”

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confidence: 99%

Regulation of endothelial connexin40 expression by shear stress

Vorderwülbecke

Maroski

Fiedorowicz

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Endothelial connexin (Cx)40 plays an important role in signal propagation along blood vessel walls, modulating vessel diameter and thereby blood flow. Blood flow, in turn, has been shown to alter endothelial Cx40 expression. However, the timing and shear stress dependence of this relationship have remained unclear, as have the signal transduction pathways involved and the functional implications. Therefore, the aim of this study was to quantify the effects of shear stress on endothelial Cx40 expression, to analyze the role of phosphoinositide 3-kinase (PI3K)/Akt signaling involved, and to assess the possible functional consequences for the adaptation of microvascular networks. First-passage human umbilical vein endothelial cells were exposed to defined shear stress conditions and analyzed for Cx40 using real-time RT-PCR and immunoblot analysis. Shear stress caused long-term induction of Cx40 protein expression, with two short-term mRNA peaks at 4 and 16 h, indicating the dynamic nature of the adaptation process. Maximum shear stress-dependent induction was observed at shear levels between 6 and 10 dyn/cm(2). Simulation of this pattern of shear-dependent Cx expression in a vascular adaptation model of a microvascular network led to an improved fit for the simulated results to experimental measurements. Cx40 expression was greatly reduced by inhibiting PI3K or Akt, with PI3K activity being required for basal Cx40 expression and Akt activity taking part in its shear stress-dependent induction.

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Differential Endothelial Gap Junction Expression in Venous Vessels Exposed to Different Hemodynamics

Cited by 12 publications

References 29 publications

Endothelial connexins in vascular function

Endothelial connexins in vascular function

Absence of venous valves in mice lacking Connexin37

Regulation of endothelial connexin40 expression by shear stress

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