Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/44855
Title: Transient High Salt Intake Promotes T-Cell-Mediated Hypertensive Vascular Injury
Authors: Yakoub, Mina
Rahman, Masudur
Kleimann, Patricia
Hoffe, Jasmina
Feige, Milena
Bouvain, Pascal
Alter, Christina
Kluczny, Jennifer Isabel
Reidel, Sophia
Nederlof, Rianne
Hering, Lydia
Argov, Doron
Arifaj, Denada
Kantauskaite, Marta
Meister, Jaroslawna
KLEINEWIETFELD, Markus 
Rump, Lars Christian
Jantsch, Jonathan
Floegel, Ulrich
Mueller, Dominik N.
Temme, Sebastian
Stegbauer, Johannes
Issue Date: 2024
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Source: Hypertension, 81 (12) , p. 2415 -2429
Abstract: BACKGROUND:Dietary high salt (HS) intake has a strong impact on cardiovascular diseases. Here, we investigated the link between HS-aggravated immune responses and the development of hypertensive vascular disease.METHODS:ApolipoproteinE-deficient mice were transiently treated with HS (1% NaCl) via drinking water for 2 weeks, followed by a washout period, and subsequent Ang II (angiotensin II) infusion (1000 ng/kg per min for 10 days) to induce abdominal aortic aneurysms/dissections and inflammation.RESULTS:While transient HS intake alone triggered nonpathologic infiltration of activated T cells into the aorta, subsequent Ang II infusion increased mortality and the incidence of abdominal aortic aneurysms/dissections and atherosclerosis compared with hypertensive control mice. There were no differences in blood pressure between both groups. In transient HS-treated hypertensive mice, the aortic injury was associated with increased inflammation, accumulation of neutrophils, monocytes, CD69+CD4+ T cells, as well as CD4+ and CD8+ memory T cells. Mechanistically, transient HS intake increased expression levels of aortic ROR gamma t as well as splenic CD4+TH17 and CD8+TC1 T cells in Ang II-treated mice. Isolated aortas of untreated mice were incubated with supernatants of TH17, TH1, or TC1 cells polarized in vitro under HS or normal conditions which revealed that secreted factors of HS-differentiated TH17 and TC1 cells, but not TH1 cells accelerated endothelial dysfunction.CONCLUSIONS:Our data suggest that transient HS intake induces a subclinical T-cell-mediated aortic immune response, which is enhanced by Ang II. We propose a 2-hit model, in which HS acts as a predisposing factor to enhance hypertension-induced TH17 and TC1 polarization and aortic disease.
Notes: Stegbauer, J (corresponding author), Heinrich Heine Univ, Univ Hosp, Fac Med, Dept Nephrol, Univ Str 1, D-40225 Dusseldorf, Germany.
johannes.stegbauer@med.uni-duesseldorf.de
Keywords: aortic aneurysm;hypertension;memory T cells;salt;vascular diseases
Document URI: http://hdl.handle.net/1942/44855
ISSN: 0194-911X
e-ISSN: 1524-4563
DOI: 10.1161/HYPERTENSIONAHA.124.23115
ISI #: WOS:001359306700017
Rights: 2024 American Heart Association, Inc
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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