Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/241731
Type: Artigo de periódico
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
II; 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: Ii-induced Hypertension
Arterial Stiffness
Aortic Stiffness
Angiotensin-ii
Rheumatoid-arthritis
T-cells
Antioxidant Supplements
Endothelial Dysfunction
Hydrogen-peroxide
Inflammation
Country: ANN ARBOR
Editor: AMER SOC CLINICAL INVESTIGATION INC
Citation: Immune Activation Caused By Vascular Oxidation Promotes Fibrosis And Hypertension. Amer Soc Clinical Investigation Inc, v. 126, p. 50-67 JAN-2016.
Rights: aberto
Identifier DOI: 10.1172/JCI80761
Address: https://www.jci.org/articles/view/80761
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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