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

Nataša Kozina,Mirela Baus Lončar,Anita Horvatić,Helena Justić,Anita Matić,Ivana Jukić,Srećko Gajović,Martina Mihalj,Iva Bazina,Zrinka Mihaljević,Ines Drenjančević,Mihael Mišir,Marina Radmilović,Kate Šešelja,Nikola Bijelić,Edi Rođak

doi:10.3390/ijms20205188

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.

Highlights

High salt (HS) dietary intake modifies the vascular reactivity to different physiological stimuli in different vascular beds [1,2,3,4], including cerebral circulation, affecting the magnitude of responses, as well as the mechanisms underlying vascular reactivity, even in normotensive animals and humans [5,6]
3 3oof f2265 the functional effects of dietary/genetic alterations, we examined the effect of HS intake on the caenraelbyrsailsionffacracrtovtiodlutimsseuein, rTesffp3e−/c−taivneimly.alIsncaodmdpitaiorned, ttooetvhaeliuraWteTthceonfutrnocltigornoaulpe.ffects of dietary/genetic alterations, we examined the effect of HS intake on the cerebral infarct volume in Tff3−/−/ C57BL/6N (Tff3)−/− animals
There is a significant effect of the HS diet on the structure of WT mice aortas, suggesting a protective effect of Tff3−/− depletion on vasculature; (c) carotid artery proteome analysis demonstrated a very complex interaction of gene depletion and diet, involving networks of structural, smooth muscle-related, and structural neuronal proteins, and innate immunity and inflammatory. (d) Interestingly, stroke was similar in both groups of animals on HS diet, suggesting that HS diet did not aggravate the effects of ischemia in both experimental groups

Summary

Introduction

High salt (HS) dietary intake modifies the vascular reactivity to different physiological stimuli in different vascular beds [1,2,3,4], including cerebral circulation, affecting the magnitude of responses, as well as the mechanisms underlying vascular reactivity, even in normotensive animals and humans [5,6]. FID represents an important physiological regulator of tissue perfusion, including cerebral circulation [8,9,10]. Many biological processes involving the interaction of neurons, glia, vascular cells and matrix components, increased oxidative stress, and inflammation have an important role in tissue injury and repair and are involved in the pathogenesis and consequences of stroke [12]. The carotid artery represents a good model for studying all complex processes involved in development and outcomes of stroke

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