PMID- 31635131 OWN - NLM STAT- MEDLINE DCOM- 20200227 LR - 20200227 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 20 DP - 2019 Oct 19 TI - Impact of High Salt Diet on Cerebral Vascular Function and Stroke in Tff3(-/-)/C57BL/6N Knockout and WT (C57BL/6N) Control Mice. LID - 10.3390/ijms20205188 [doi] LID - 5188 AB - 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. FAU - Kozina, Natasa AU - Kozina N AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Physiology and Immunology, J. Huttlera 4, HR-31000 Osijek, Croatia. natasa.kozina@mefos.hr. FAU - Mihaljevic, Zrinka AU - Mihaljevic Z AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Physiology and Immunology, J. Huttlera 4, HR-31000 Osijek, Croatia. zrinka.mihaljevic@mefos.hr. FAU - Loncar, Mirela Baus AU - Loncar MB AUID- ORCID: 0000-0002-6940-2302 AD - Ruder Boskovic Institute, Department of Molecular Medicine; Bijenicka 54, HR-10000 Zagreb, Croatia. mbaus@irb.hr. FAU - Mihalj, Martina AU - Mihalj M AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Physiology and Immunology, J. Huttlera 4, HR-31000 Osijek, Croatia. martina.mihalj@mefos.hr. AD - Clinical Hospital Center Osijek, Dept of Dermatology and Venerology, J. Huttlera 4, HR-31000 Osijek, Croatia. martina.mihalj@mefos.hr. FAU - Misir, Mihael AU - Misir M AD - Clinical Hospital Center Osijek, Neurology Clinic, J. Huttlera 4, HR-31000 Osijek, Croatia. mihaelmisir@gmail.com. FAU - Radmilovic, Marina Dobrivojevic AU - Radmilovic MD AD - University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Zagreb, Croatia, Salata 12, HR-10000 Zagreb, Croatia. marina.radmilovic@mef.hr. FAU - Justic, Helena AU - Justic H AD - University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Zagreb, Croatia, Salata 12, HR-10000 Zagreb, Croatia. helena.justic@mef.hr. FAU - Gajovic, Srecko AU - Gajovic S AUID- ORCID: 0000-0001-8668-5239 AD - University of Zagreb, School of Medicine, Croatian Institute for Brain Research, Zagreb, Croatia, Salata 12, HR-10000 Zagreb, Croatia. srecko.gajovic@hiim.hr. FAU - Seselja, Kate AU - Seselja K AD - Ruder Boskovic Institute, Department of Molecular Medicine; Bijenicka 54, HR-10000 Zagreb, Croatia. kseselja@irb.hr. FAU - Bazina, Iva AU - Bazina I AD - Ruder Boskovic Institute, Department of Molecular Medicine; Bijenicka 54, HR-10000 Zagreb, Croatia. ibazina@irb.hr. FAU - Horvatic, Anita AU - Horvatic A AUID- ORCID: 0000-0001-9625-1450 AD - Proteomics laboratory, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55 HR-10000 Zagreb, Croatia. horvatic.ani@gmail.com. FAU - Matic, Anita AU - Matic A AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Physiology and Immunology, J. Huttlera 4, HR-31000 Osijek, Croatia. acosic@mefos.hr. FAU - Bijelic, Nikola AU - Bijelic N AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Histology and Embriology, J. Huttlera 4, HR-31000 Osijek, Croatia. nbijelic@mefos.hr. FAU - Rodak, Edi AU - Rodak E AUID- ORCID: 0000-0001-7814-2031 AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Histology and Embriology, J. Huttlera 4, HR-31000 Osijek, Croatia. erodak@mefos.hr. FAU - Jukic, Ivana AU - Jukic I AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Physiology and Immunology, J. Huttlera 4, HR-31000 Osijek, Croatia. ivana.jukic@mefos.hr. FAU - Drenjancevic, Ines AU - Drenjancevic I AD - Faculty of Medicine Osijek, University Josip Juraj Strossmayer Osijek, Institute and Dept of Physiology and Immunology, J. Huttlera 4, HR-31000 Osijek, Croatia. ines.drenjancevic@mefos.hr LA - eng PT - Journal Article DEP - 20191019 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - 0 (DNA-Binding Proteins) RN - 0 (Elf2 protein, mouse) RN - 0 (Proteome) RN - 0 (Sodium Chloride, Dietary) RN - 0 (Tff3 protein, mouse) RN - 0 (Transcription Factors) RN - 0 (Trefoil Factor-3) RN - 31C4KY9ESH (Nitric Oxide) SB - IM MH - Animals MH - Biomarkers MH - Carotid Arteries/drug effects/metabolism MH - Cerebrovascular Circulation/*drug effects MH - DNA-Binding Proteins/metabolism MH - Diet MH - Disease Models, Animal MH - Endoplasmic Reticulum Stress/drug effects/genetics MH - Endothelium, Vascular/metabolism MH - Immunohistochemistry MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Nitric Oxide/metabolism MH - Proteome MH - Regional Blood Flow MH - Sodium Chloride, Dietary/*pharmacology MH - Stroke/*etiology/*physiopathology MH - Transcription Factors/metabolism MH - Trefoil Factor-3/*deficiency MH - Vasodilation/drug effects PMC - PMC6829871 OTO - NOTNLM OT - Tff3 gene OT - flow-induced dilation OT - high salt diet OT - stroke COIS- The authors declare no conflicts of interest. EDAT- 2019/10/23 06:00 MHDA- 2020/02/28 06:00 PMCR- 2019/10/01 CRDT- 2019/10/23 06:00 PHST- 2019/07/29 00:00 [received] PHST- 2019/09/20 00:00 [revised] PHST- 2019/10/05 00:00 [accepted] PHST- 2019/10/23 06:00 [entrez] PHST- 2019/10/23 06:00 [pubmed] PHST- 2020/02/28 06:00 [medline] PHST- 2019/10/01 00:00 [pmc-release] AID - ijms20205188 [pii] AID - ijms-20-05188 [pii] AID - 10.3390/ijms20205188 [doi] PST - epublish SO - Int J Mol Sci. 2019 Oct 19;20(20):5188. doi: 10.3390/ijms20205188.