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The role of wall shear stress on cerebral aneurysm development via P2X4 ion channel, a sensor for shear stress mechanotransduction, in vascular endothelial cells (LB669)
Author(s) -
Fukuda Miyuki,
Fukuda Shunichi,
Ando Joji,
Hasegawa Koji
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb669
Subject(s) - aneurysm , mechanotransduction , shear stress , ion channel , internal elastic lamina , endothelium , medicine , biophysics , cardiology , anatomy , microbiology and biotechnology , materials science , chemistry , biology , surgery , artery , composite material , receptor
[Objective] Our study using an animal model of experimentally induced cerebral aneurysms suggests that perception of an excessive increase in wall shear stress (WSS) by endothelial cells initiates the arterial wall degeneration caused by expression of various enzymes, leading to aneurysm development. Our computational fluid dynamics analysis also demonstrated that the magnitude of WSS is enhanced at the site where human aneurysms develop. In this study, we examine the role of WSS on cerebral aneurysm formation, using a shear sensor, P2X4 purinoceptor deficient mice (P2X4 KO). [Methods] P2X4 KO (n = 19) and wild types (n = 21) were used for aneurysm‐inducing surgery as described before. Aneurysm as defined here refers to an outward bulging detected by light microscopy (more than 10 um). Damage to internal elastic lamina as early aneurysm changes was classified into 3 grades according to microscopic pathological changes. [Result] The grade of damage in P2X4 KO group was significantly lower than that in wild type group (p = 0.027). Moreover, the incidence of induced aneurysm formation in P2X4 KO group was significantly below that in wild type group (p = 0.018). [Conclusion] The data suggest that blockage of a shear‐sensor, P2X4 ion channels, causes the suppression of WSS mechanotransduction, leading to aneurysm formation.