Transient high salt intake promotes T-cell-mediated hypertensive vascular injury

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Item Type:	Article
Title:	Transient high salt intake promotes T-cell-mediated hypertensive vascular injury
Creators Name:	Yakoub, M., Rahman, M., Kleimann, P., Hoffe, J., Feige, M., Bouvain, P., Alter, C., Kluczny, J.I., Reidel, S., Nederlof, R., Hering, L., Argov, D., Arifaj, D., Kantauskaite, M., Meister, J., Kleinewietfeld, M., Rump, L.C., Jantsch, J., Flögel, U., Müller, D.N., Temme, S. and Stegbauer, J.
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 RORγt as well as splenic CD4(+)T(H)17 and CD8(+)T(C)1 T cells in Ang II-treated mice. Isolated aortas of untreated mice were incubated with supernatants of T(H)17, T(H)1, or T(C)1 cells polarized in vitro under HS or normal conditions which revealed that secreted factors of HS-differentiated T(H)17 and T(C)1 cells, but not T(H)1 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 T(H)17 and TC(1) polarization and aortic disease.
Keywords:	Aortic Aneurysm, Effector Memory Cells, Hypertension, Salt, Vascular Inflammation, Animals, Mice
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	81
Number:	12
Page Range:	2415-2429
Date:	December 2024
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.124.23115
PubMed:	View item in PubMed

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