Cargando…

Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ

Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial...

Descripción completa

Detalles Bibliográficos
Autores principales: Vecchione, Carmine, Patrucco, Enrico, Marino, Gennaro, Barberis, Laura, Poulet, Roberta, Aretini, Alessandra, Maffei, Angelo, Gentile, Maria Teresa, Storto, Marianna, Azzolino, Ornella, Brancaccio, Mara, Colussi, Gian Luca, Bettarini, Umberto, Altruda, Fiorella, Silengo, Lorenzo, Tarone, Guido, Wymann, Mathias P., Hirsch, Emilio, Lembo, Giuseppe
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213159/
https://www.ncbi.nlm.nih.gov/pubmed/15824082
http://dx.doi.org/10.1084/jem.20040995
_version_ 1782148837729632256
author Vecchione, Carmine
Patrucco, Enrico
Marino, Gennaro
Barberis, Laura
Poulet, Roberta
Aretini, Alessandra
Maffei, Angelo
Gentile, Maria Teresa
Storto, Marianna
Azzolino, Ornella
Brancaccio, Mara
Colussi, Gian Luca
Bettarini, Umberto
Altruda, Fiorella
Silengo, Lorenzo
Tarone, Guido
Wymann, Mathias P.
Hirsch, Emilio
Lembo, Giuseppe
author_facet Vecchione, Carmine
Patrucco, Enrico
Marino, Gennaro
Barberis, Laura
Poulet, Roberta
Aretini, Alessandra
Maffei, Angelo
Gentile, Maria Teresa
Storto, Marianna
Azzolino, Ornella
Brancaccio, Mara
Colussi, Gian Luca
Bettarini, Umberto
Altruda, Fiorella
Silengo, Lorenzo
Tarone, Guido
Wymann, Mathias P.
Hirsch, Emilio
Lembo, Giuseppe
author_sort Vecchione, Carmine
collection PubMed
description Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)γ are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kγ was found to play a role in angiotensin II–evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kγ was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kγ was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca(2+) channel–mediated extracellular Ca(2+) entry. These data indicate that PI3Kγ is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kγ function might be exploited to improve therapeutic intervention on hypertension.
format Text
id pubmed-2213159
institution National Center for Biotechnology Information
language English
publishDate 2005
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-22131592008-03-11 Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ Vecchione, Carmine Patrucco, Enrico Marino, Gennaro Barberis, Laura Poulet, Roberta Aretini, Alessandra Maffei, Angelo Gentile, Maria Teresa Storto, Marianna Azzolino, Ornella Brancaccio, Mara Colussi, Gian Luca Bettarini, Umberto Altruda, Fiorella Silengo, Lorenzo Tarone, Guido Wymann, Mathias P. Hirsch, Emilio Lembo, Giuseppe J Exp Med Article Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)γ are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kγ was found to play a role in angiotensin II–evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kγ was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kγ was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca(2+) channel–mediated extracellular Ca(2+) entry. These data indicate that PI3Kγ is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kγ function might be exploited to improve therapeutic intervention on hypertension. The Rockefeller University Press 2005-04-18 /pmc/articles/PMC2213159/ /pubmed/15824082 http://dx.doi.org/10.1084/jem.20040995 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Vecchione, Carmine
Patrucco, Enrico
Marino, Gennaro
Barberis, Laura
Poulet, Roberta
Aretini, Alessandra
Maffei, Angelo
Gentile, Maria Teresa
Storto, Marianna
Azzolino, Ornella
Brancaccio, Mara
Colussi, Gian Luca
Bettarini, Umberto
Altruda, Fiorella
Silengo, Lorenzo
Tarone, Guido
Wymann, Mathias P.
Hirsch, Emilio
Lembo, Giuseppe
Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
title Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
title_full Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
title_fullStr Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
title_full_unstemmed Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
title_short Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
title_sort protection from angiotensin ii–mediated vasculotoxic and hypertensive response in mice lacking pi3kγ
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213159/
https://www.ncbi.nlm.nih.gov/pubmed/15824082
http://dx.doi.org/10.1084/jem.20040995
work_keys_str_mv AT vecchionecarmine protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT patruccoenrico protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT marinogennaro protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT barberislaura protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT pouletroberta protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT aretinialessandra protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT maffeiangelo protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT gentilemariateresa protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT stortomarianna protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT azzolinoornella protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT brancacciomara protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT colussigianluca protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT bettariniumberto protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT altrudafiorella protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT silengolorenzo protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT taroneguido protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT wymannmathiasp protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT hirschemilio protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg
AT lembogiuseppe protectionfromangiotensiniimediatedvasculotoxicandhypertensiveresponseinmicelackingpi3kg