Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation

Publication Date:
2018-10-02
Publisher:
Rockefeller University Press
Print ISSN:
0022-1007
Electronic ISSN:
1540-9538
Topics:
Medicine
Keywords:
Cardiovascular Biology
Published by:
http://www.rupress.org/
_version_ 1836399060602322946
autor Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
beschreibung The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-B activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y 2 receptor, and G q /G 11 -mediated signaling. However, only disturbed flow leads to Piezo1- and G q /G 11 -mediated integrin activation resulting in focal adhesion kinase-dependent NF-B activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα q /Gα 11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
citation_standardnr 6339710
datenlieferant ipn_articles
feed_id 96
feed_publisher Rockefeller University Press
feed_publisher_url http://www.rupress.org/
insertion_date 2018-10-02
journaleissn 1540-9538
journalissn 0022-1007
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher Rockefeller University Press
quelle Journal of Experimental Medicine
relation http://jem.rupress.org/cgi/content/short/215/10/2655?rss=1
schlagwort Cardiovascular Biology
search_space articles
shingle_author_1 Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
shingle_author_2 Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
shingle_author_3 Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
shingle_author_4 Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
shingle_catch_all_1 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
Cardiovascular Biology
The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-B activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y 2 receptor, and G q /G 11 -mediated signaling. However, only disturbed flow leads to Piezo1- and G q /G 11 -mediated integrin activation resulting in focal adhesion kinase-dependent NF-B activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα q /Gα 11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_catch_all_2 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
Cardiovascular Biology
The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-B activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y 2 receptor, and G q /G 11 -mediated signaling. However, only disturbed flow leads to Piezo1- and G q /G 11 -mediated integrin activation resulting in focal adhesion kinase-dependent NF-B activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα q /Gα 11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_catch_all_3 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
Cardiovascular Biology
The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-B activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y 2 receptor, and G q /G 11 -mediated signaling. However, only disturbed flow leads to Piezo1- and G q /G 11 -mediated integrin activation resulting in focal adhesion kinase-dependent NF-B activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα q /Gα 11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_catch_all_4 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
Cardiovascular Biology
The vascular endothelium is constantly exposed to mechanical forces, including fluid shear stress exerted by the flowing blood. Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-B activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y 2 receptor, and G q /G 11 -mediated signaling. However, only disturbed flow leads to Piezo1- and G q /G 11 -mediated integrin activation resulting in focal adhesion kinase-dependent NF-B activation. Mice with induced endothelium-specific deficiency of Piezo1 or Gα q /Gα 11 show reduced integrin activation, inflammatory signaling, and progression of atherosclerosis in atheroprone areas. Our data identify critical steps in endothelial mechanotransduction, which distinguish flow pattern-dependent activation of atheroprotective and atherogenic endothelial signaling and suggest novel therapeutic strategies to treat inflammatory vascular disorders such as atherosclerosis.
Albarran-Juarez, J., Iring, A., Wang, S., Joseph, S., Grimm, M., Strilic, B., Wettschureck, N., Althoff, T. F., Offermanns, S.
Rockefeller University Press
0022-1007
00221007
1540-9538
15409538
shingle_title_1 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
shingle_title_2 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
shingle_title_3 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
shingle_title_4 Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
timestamp 2025-06-30T23:36:58.748Z
titel Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
titel_suche Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation
topic WW-YZ
uid ipn_articles_6339710