Program

PO1-2-46

Endothelial cell reduces gap junction intercellular communication and increases cellular stiffness upon inflammation

[Speaker] Takayuki Okamoto:1
[Co-author] Eiji Kawamoto:2,3, Haruki Usuda:1, Motomu Shimaoka:2, Koichiro Wada:1
1:Shimane University Faculty of Medicine, Japan, 2:Mie University Graduate School of Medicine, Japan, 3:Mie University Hospital, Japan

Arterial stiffening has been observed during atherosclerosis and is a cholesterol-independent risk factor for cardiovascular events. Arterial stiffness is determined by the composition of matrix components in the vascular wall. In addition to the reconstitution of matrix components, the increased stiffness of vascular smooth muscle cells has also been associated with aging-related arterial stiffening, whereas the alteration and contribution of endothelial cellular stiffness have only been assumed from several in vitro and in vivo findings. Endothelial cellular stiffness has been shown to be affected by the substrate stiffness, shear stress, and other factors; however, the impact of vascular inflammation on endothelial cell stiffness remains poorly understood.
To study endothelial cell stiffness, we have measured the force curve of live human umbilical vein endothelial cells (HUVECs) by using atomic force microscopy. We have shown that stimulation of HUVECs with tumor necrosis factor-alpha increased the endothelial cellular stiffness. The increase in stiffness was transient, thereby peaking at 4 h after stimulation and returning to the baseline stiffness after 24 h. Next we have observed that upon the formation of a confluent monolayer, HUVEC decreased its stiffness. This result led us to investigate how cell-cell interactions would contribute to endothelial cellular stiffness. Then we have shown that a gap junction inhibitor facilitates endothelial cell stiffening.
Abnormal expression and dysfunction of endothelial gap junction have been associated with the onset of cardiovascular diseases. Supported by our previous report that endothelial gap junction is suppressed after inflammatory stimulation, the present results suggest that endothelial cell increases the cellular stiffness in response to inflammatory stimuli through impairment of gap junction. Our study provides a new insight into the potential pathogenic role of endothelial cellular stiffness driven by vascular inflammation.
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