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

• Published in: International journal of molecular sciences 2019-10, Vol.20 (20), p.5188
• Main Authors: Kozina, Nataša, Mihaljević, Zrinka, Lončar, Mirela Baus, Mihalj, Martina, Mišir, Mihael, Radmilović, Marina Dobrivojević, Justić, Helena, Gajović, Srećko, Šešelja, Kate, Bazina, Iva, Horvatić, Anita, Matić, Anita, Bijelić, Nikola, Rođak, Edi, Jukić, Ivana, Drenjančević, Ines
• Format: Article
• Language: English
• Subjects: Acetylcholine; Animals; Arachidonic acid; Biomarkers; Carotid arteries; Carotid Arteries - drug effects; Carotid Arteries - metabolism; Cerebral blood flow; Cerebrovascular Circulation - drug effects; Cytokines; Depletion; Diet; Dietary intake; Dilation; Disease Models, Animal; DNA-Binding Proteins - metabolism; Endoplasmic Reticulum Stress - drug effects; Endoplasmic Reticulum Stress - genetics; Endothelium; Endothelium, Vascular - metabolism; Enzymes; flow-induced dilation; Genes; Heat shock proteins; high salt diet; Immune response; Immunohistochemistry; Inflammation; Innate immunity; Ischemia; Keratin; Lipid metabolism; Lipids; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric oxide; Nitric Oxide - metabolism; Nutrient deficiency; Occlusion; Oxidative stress; Physiology; Polypeptides; Protein expression; Proteome; Proteomes; Regional Blood Flow; Rodents; Salt; Sodium chloride; Sodium Chloride, Dietary - pharmacology; Stroke; Stroke - etiology; Stroke - physiopathology; Stroke volume; Structural proteins; tff3 gene; Transcription Factors - metabolism; Transgenic mice; Trefoil Factor-3 - deficiency; Tumor necrosis factor-TNF; Vasodilation - drug effects; Veins & arteries
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20205188

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 gene knockout mice ( 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 and wild type (WT/C57BL/6N) mice. Flow-induced dilation (FID) of carotid artery was reduced in WT-HS mice, but not affected in HS mice. Nitric oxide (NO) mediated FID. NO production was decreased with HS diet. On the contrary, acetylcholine-induced dilation was significantly decreased in mice on both diets and WT-HS mice. HS intake and gene depletion affected the structural components of the vessels. Proteomic analysis revealed a significant effect of gene deficiency on HS diet-induced changes in neuronal structural proteins and acute innate immune response proteins' expression and 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, depletion seems to partially impair vascular function and worsen the outcomes of stroke, which is moderately affected by HS diet.