Gap junction-mediated regulation of endothelial cellular stiffness

Abstract

Endothelial monolayers have shown the ability to signal each other through gap junctions. Gap junction-mediated cell-cell interactions have been implicated in the modulation of endothelial cell functions during vascular inflammation. Inflammatory mediators alter the mechanical properties of endothelial cells, although the exact role of gap junctions in this process remains unclear. Here, we sought to study the role of gap junctions in the regulation of endothelial stiffness, an important physical feature that is associated with many vascular pathologies. The endothelial cellular stiffness of living endothelial cells was determined by using atomic force microscopy. We found that tumor necrosis factor-α transiently increased endothelial cellular stiffness, which is regulated by cytoskeletal rearrangement and cell-cell interactions. We explored the role of gap junctions in endothelial cellular stiffening by utilizing gap junction blockers, carbenoxolone, inhibitory anti-connexin 32 antibody or anti-connexin 43 antibody. Blockade of gap junctions induced the cellular stiffening associated with focal adhesion formation and cytoskeletal rearrangement, and prolonged tumor necrosis factor-α-induced endothelial cellular stiffening. These results suggest that gap junction-mediated cell-cell interactions play an important role in the regulation of endothelial cellular stiffness.

Connexin43 Hemichannel Targeting With TAT-Gap19 Alleviates Radiation-Induced Endothelial Cell Damage

“…Cx43 also has atherogenic properties as decreasing Cx43 expression reduces the formation of atherosclerotic lesions in vivo (Kwak et al, 2003;Wong et al, 2003;Wang et al, 2013b) while in vivo Cx43 upregulation increased the expression of cell adhesion proteins such as VCAM-1, thereby enhancing monocyte-endothelial adhesion, a key event in initiating atherosclerosis (Yuan et al, 2015). Furthermore, Cx43 has been implicated in endothelial cellular stiffness that is associated with cardiovascular disease and atherosclerosis (Okamoto et al, 2017).…”

The Functional Implication for Endothelial Gap Junction and Cellular Mechanics in Vascular Angiogenesis

“…Thus, interplay between endothelial Cxs and Rho family has implicated in the regulation of cellular stiffness. We have found that proinflammatory stimulation increased endothelial cellular stiffness associating with impaired GJ function, cytoskeletal remodeling, and focal adhesion formation [98].…”

“…Moreover, blockade of GJs induces the cellular stiffening associated with focal adhesion formation and cytoskeletal rearrangement, and prolonges TNF-α-induced endothelial cellular stiffening [98].…”

Gene expression profiles of glucose toxicity‐exposed islet microvascular endothelial cells

“…In addition, β1‐integrin‐matrix interactions modulated microvascular endothelial cell tight junction and permeability which was important for maintaining the hydrostatic pressure in the normal range . Furthermore, gap junction‐mediated cell‐cell interaction had been implicated in the modulation of endothelial cell functions . Therefore, microvascular endothelial cell function‐related mRNAs may be involved in the glucose toxicity‐induced impairment.…”

“…29 Furthermore, gap junction-mediated cell-cell interaction had been implicated in the modulation of endothelial cell functions. 30 Therefore, microvascular endothelial cell function-related mRNAs may be involved in the glucose toxicity-induced impairment.…”