Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/355317
Type: Artigo
Title: Immune activation caused by vascular oxidation promotes fibrosis and hypertension
Author: Wu, Jing
Saleh, Mohamed A.
Kirabo, Annet
Itani, Hana A.
Montaniel, Kim Ramil C.
Xiao, Liang
Chen, Wei
Mernaugh, Raymond L.
Cai, Hua
Bernstein, Kenneth E.
Goronzy, Joerg J.
Weyand, Cornelia M.
Curci, John A.
Barbaro, Natalia R.
Moreno, Heitor
Davies, Sean S.
Roberts, L. Jackson
Madhur, Meena S.
Harrison, David G.
Abstract: Vascular oxidative injury accompanies many common conditions associated with hypertension. In the present study, we employed mouse models with excessive vascular production of ROS (tg(sm/p22phox) mice, which overexpress the NADPH oxidase subunit p22(phox) smooth muscle, and mice with vascular-specific deletion of extracellular SOD) and have shown that these animals develop vascular collagen deposition, aortic stiffening, renal dysfunction, and hypertension with age. T cells from tg(5m/p22phox) mice produced high levels of IL-17A and IFN-gamma. Crossing tg(sm/p22phox) mice with lymphocyte-deficient Rag1(-/-) mice eliminated vascular inflammation, aortic stiffening, renal dysfunction, and hypertension; however, adoptive transfer of T cells restored these processes. Isoketal-protein adducts, which are immunogenic, were increased in aortas, DCs, and macrophages of tg(sm/P22Phox) mice. Autologous pulsing with tg(sm/p22phox) aortic homogenates promoted DCs of tg(sm/p22phox) mice to stimulate T cell proliferation and production of IFN-gamma, IL-17A, and TNF-alpha. Treatment with the superoxide scavenger tempol or the isoketal scavenger 2-hydroxybenzylamine (2-HOBA) normalized blood pressure; prevented vascular inflammation, aortic stiffening, and hypertension; and prevented DC and T cell activation. Moreover, in human aortas, the aortic content of isoketal adducts correlated with fibrosis and inflammation severity. Together, these results define a pathway linking vascular oxidant stress to immune activation and aortic stiffening and provide insight into the systemic inflammation encountered in common vascular diseases
Subject: Artrite reumatóide
Hipertensão
Rigidez vascular
Disfunção endotelial
Country: Estados Unidos
Editor: American Society for Clinical Investigation
Rights: Aberto
Identifier DOI: 10.1172/JCI80761
10.1172/JCI87425
Address: https://www.jci.org/articles/view/80761
https://www.jci.org/articles/view/87425
Date Issue: 2016
Appears in Collections:FCM - Artigos e Outros Documentos

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