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Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3−/−/C57BL/6N Knockout and WT (C57BL/6N) Control Mice

Kozina, Nataša; Mihaljević, Zrinka; Baus Lončar, Mirela; Mihalj, Martina; Mišir, Mihael; Radmilović, Marina; Justić, Helena; Gajović, Srećko; Šešelja, Kate; Bazina, Iva; Horvatić, Anita; Matić, Anita; Bijelić, Nikola; Rođak, Edi; Jukić, Ivana; Drenjančević, Ines (2019) Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3−/−/C57BL/6N Knockout and WT (C57BL/6N) Control Mice. International Journal of Molecular Sciences, 20 (20). ISSN 1661-6596

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Abstract

High salt (HS) dietary intake leads to impaired vascular endothelium-dependent responses to various physiological stimuli, some of which are mediated by arachidonic acid (AA) metabolites. Transgenic Tff3−/− gene knockout mice (Tff3−/−/C57BL/6N) have changes in lipid metabolism which may affect vascular function and outcomes of stroke. We aimed to study the effects of one week of HS diet (4% NaCl) on vascular function and stroke induced by transient occlusion of middle cerebral artery in Tff3−/− and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in Tff3−/−-HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in Tff3−/− mice on both diets and WT-HS mice. HS intake and Tff3 gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of Tff3 gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins’ expression and Tff3 depletion, but HS diet did not increase the stroke volume, which is related to proteome modification and upregulation of genes involved mainly in cellular antioxidative defense. In conclusion, Tff3 depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.

Item Type: Article
Uncontrolled Keywords: Tff3 gene ; flow-induced dilation ; high salt diet ; stroke
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
poremećena vazorelaksacija i endotelno-leukocitna interakcija (ELI) u razvoju aterosklerotskih lezija-V-ELI AtheroInes DrenjančevićIP-2014-09-6380HRZZ
Depositing User: Mirela Baus Lončar
Date Deposited: 06 Dec 2019 16:10
Last Modified: 06 Dec 2019 16:12
URI: http://fulir.irb.hr/id/eprint/5240
DOI: 10.3390/ijms20205188

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