| 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 |
| Contributors: |
Kleimann, Patricia/0009-0009-8917-4229; Rahman; Masudur/0009-0006-9429-6405; Hoffe, Jasmina/0009-0005-6433-9219; Yakoub; Mina/0009-0002-3405-2864; 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 |
| Publisher Information: |
LIPPINCOTT WILLIAMS & WILKINS |
| Publication Year: |
2024 |
| Collection: |
Document Server@UHasselt (Universiteit Hasselt) |
| Subject Terms: |
aortic aneurysm; hypertension; memory T cells; salt; vascular diseases |
| Description: |
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. ; This work was supported by the German Research Foundation (CRC 1116 to U. Flögel; CRC 259 to U. Flögel; CRC1470 A06 to D.N. Müller; FL303/6- 1/2 to U. Flögel; INST 208/764-1 FUGG to U. Flögel; TE1209/1-1/2 to S. Temme; IRTG1902 to J. Stegbauer, STE2042/2-1 to J. ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
info:eu-repo/grantAgreement/EC/H2020/Project ID, 640116; https://hdl.handle.net/1942/44855; 2429; 12; 2415; 81; WOS:001359306700017 |
| DOI: |
10.1161/HYPERTENSIONAHA.124.23115 |
| Availability: |
https://hdl.handle.net/1942/44855; https://doi.org/10.1161/HYPERTENSIONAHA.124.23115 |
| Accession Number: |
edsbas.7818AA2C |
| Database: |
BASE |