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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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yakoub-et-al-2024-transient-high-salt-intake-promotes-t-cell-mediated-hypertensive-vascular-injury.pdf Restricted Access | Published version | 7.86 MB | Adobe PDF | View/Open Request a copy |
xx.pdf | Peer-reviewed author version | 3.92 MB | Adobe PDF | View/Open |
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