HomeArteriosclerosis, Thrombosis, and Vascular BiologyAhead of PrintSMIT1 Expression in Arterial Tissue: A Potential New Trigger of Vascular Dysfunctions and ROS Production in Rats No AccessLetterRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessLetterRequest AccessSMIT1 Expression in Arterial Tissue: A Potential New Trigger of Vascular Dysfunctions and ROS Production in Rats Antoine Grandperrin, Eva Strock, Léna Petit, Sydney Risdon, Doria Boulghobra, Sandrine Gayrard, Cyril Reboul, Guillaume Walther, Sylvain Battault and Gregory Meyer Antoine GrandperrinAntoine Grandperrin UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Eva StrockEva Strock UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Léna PetitLéna Petit https://orcid.org/0000-0003-1315-5821 UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Sydney RisdonSydney Risdon UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Doria BoulghobraDoria Boulghobra UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Sandrine GayrardSandrine Gayrard https://orcid.org/0009-0008-4103-4182 UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Cyril ReboulCyril Reboul https://orcid.org/0000-0001-5181-3827 UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Guillaume WaltherGuillaume Walther https://orcid.org/0000-0001-7604-8973 UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. , Sylvain BattaultSylvain Battault https://orcid.org/0000-0003-2934-2314 UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. and Gregory MeyerGregory Meyer Correspondence to: Gregory Meyer, UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, F-84000 Avignon, France. Email E-mail Address: [email protected] https://orcid.org/0000-0003-3199-1364 UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, France. Originally published14 Mar 2024https://doi.org/10.1161/ATVBAHA.123.320547Arteriosclerosis, Thrombosis, and Vascular Biology. 2024;0FootnotesFor Sources of Funding and Disclosures, see page XXX.*A. Grandperrin and E. Strock contributed equally.Correspondence to: Gregory Meyer, UPR-4278, LaPEC, Laboratory of Cardiovascular Experimental Physiology, Avignon University, F-84000 Avignon, France. Email gregory.meyer@univ-avignon.fr Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2024 American Heart Association, Inc.https://doi.org/10.1161/ATVBAHA.123.320547PMID: 38482695 Originally publishedMarch 14, 2024 Keywordsendotheliumhyperglycemiareactive oxygen speciesrisk factorssodiumPDF download Advertisement SubjectsBasic Science ResearchOxidant StressVascular BiologyVascular Disease

Previous investigations from our group and others revealed that hyperglycemia (HG) impairs vascular endothelial function particularly through an increased oxidative stress. For a long time, little was known about the glucose transport mechanisms responsible for these alterations in the cardiovascular system under HG conditions. However, recent work has shown the involvement of the sodium myo-inositol transporter 1 (SMIT1) of the sodium-glucose co-transporter (SGLT) family in HG-dependent ROS production. However, few studies have focused on the involvement of these transporters in the vascular effects of HG. In this context, we aimed to evaluate the implication of the different SGLT isoforms on the increased oxidative stress and the subsequent vascular dysfunction reported during HG. Firstly, Gene expression of the 7 isoforms of SGLT Transporters was evaluated in vascular tissues by PCR. Then, in order to study the involvement of SGLT/SMIT transporters in HG-related vascular alterations, we incubated (1 hour, 100 mM) aortic rings from Wistar rats with either of the following sugars which each stimulate either one or more isoforms of these transporters (Glucose: GLUTs/SGLTs/SMITs transporters; α-MG: SGLT 1 to 5; Galactose: SGLT 1/2; myo-inositol: SMIT 1/2; L-Fucose: SMIT1). Then, incubated vessels were either mounted in organ chambers to study vascular endothelial function or embedded in OCT in order to measure reactive oxygen species (ROS) production with DHE fluorescence. First, PCR analyses highlighted that SMIT1 appears to be the transporter of the SGLT family whose gene expression is predominant in vascular tissue. As expected from previous studies, vascular exposure to glucose was responsible for an endothelial dysfunction associated with a higher ROS production. Interestingly, endothelial impairments and increased ROS production were not observed when SGLTs were stimulated with either α-MG or galactose. The main result of this work was that myo-inositol exposure was responsible for similar endothelial alteration than glucose and that L-Fucose which transport is highly dependent of SMIT1 was responsible for an exacerbation of those impairments. These results highlight the implication of SMIT1 in the increased oxidative stress and endothelial dysfunctions observed during HG in vascular tissues.

Cette dernière décennie, l’industrie agroalimentaire a largement adapté son offre avec la généralisation de produits contenant des édulcorants pour remplacer les sucres ajoutés ou sucres libres et, ainsi, limiter les apports caloriques tout en maintenant l’appétence aux produits. Cependant, nombre de données observationnelles questionnent l’efficacité et la sécurité de cette stratégie. En effet, les édulcorants semblent présenter des avantages et des inconvénients sur les plans du comportement alimentaire et des conséquences métaboliques. Cette disparité des résultats semble pouvoir s’expliquer par les mécanismes d’action et l’impact spécifique des différentes molécules édulcorantes. En effet, bien que tous les édulcorants ciblent les mêmes récepteurs cellulaires, il faut rappeler que chaque édulcorant peut différer dans sa structure chimique, son profil pharmacocinétique et, plus important encore, dans son activité pharmacologique, et ainsi induire des réponses physiologiques ou pathologiques propres. De manière générale, les méta-analyses indiquent une augmentation du risque de développer un diabète de type 2 lorsque la consommation de ces édulcorants est importante, mais les données expérimentales ne sont pas aussi tranchées. Cet article présente les mécanismes d’action des édulcorants les plus utilisés et les différents effets associés à la consommation d’édulcorants sur le comportement alimentaire et ses conséquences sur la gestion du poids et le contrôle métabolique.

Artificial sweeteners (AS) are well known to activate two categories of receptors; sweet taste receptor with high affinity and bitter taste receptors with low affinity. Interestingly, recent data from our and other groups suggested that these two receptors families are expressed throughout the arterial tree. Therefore, it could be interesting to explore if AS may have an impact on vascular function, and to decipher the role of these taste receptors. The aims of this ongoing work is to investigate whether AS, like sucralose and acesulfame potassium (AceK) (1) exhibit vasomotor effect and (2) in that case determine the underlying mechanisms. Biomolecular and functional investigations have been performed on isolated rodent aortas, human dermal micro-arteries and omental arteries. Ex vivo vasomotor function was assessed using isometric tension measurements in organ bath systems. We first confirmed that both endothelial and smooth muscle cells from rodent and human arteries express the transcripts encoding for TAS1R2 and TAS1R3; the heterodimer receptor known to be responsible for the sweet taste. Our ex vivo data showed that only high concentrations (about 10 mM) of AceK and sucralose induce vasomotor responses. While AceK exhibited a vasoconstrictive effect, sucralose induced vasorelaxation. Both responses were found to be independent of the endothelium. Pharmacological inhibition (gurmarin and lactisol) and the use of a TAS1R3 KO mice model demonstrated that AS vasomotor effects do not rely on the sweet taste receptors. In contrast, inhibition of TAS2Rs abolished all responses suggesting that bitter taste receptors are more likely responsible for the AS-induced vascular effects. Additionally, our last observations show that the vasoconstrictive effect of AceK is mediated by RhoA/ROCK pathway. These evidences support the idea that AS can alter vasomotor signaling in the smooth muscle cells. These acute effects are probably mediated by the bitter taste receptor family. Their activation at the vascular level as well as the underlying pathways remains poorly understood, and the physiopathological consequences need to be further investigated.

The excess consumption of added sugar is consistently found to be associated with weight gain, and a higher risk of type 2 diabetes mellitus, coronary heart disease, and stroke. In an effort to reduce the risk of cardiometabolic disease, sugar is frequently replaced by low- and null-calorie sweeteners (LCSs). Alarmingly, though, emerging evidence indicates that the consumption of LCSs is associated with an increase in cardiovascular mortality risk that is amplified in those who are overweight or obese. Sucralose, a null-caloric high-intensity sweetener, is the most commonly used LCS worldwide, which is regularly consumed by healthy individuals and patients with metabolic disease. To explore a potential causal role for sucralose in increased cardiovascular risk, this present review summarizes the preclinical and clinical data from current research detailing the effects of sucralose on systems controlling food intake, glucose homeostasis, and gut microbiota.

SCOPE:A main risk factor of atherosclerosis is a Western diet (WD) rich in n-6 polyunsaturated fatty acids (PUFAs) sensitive to oxidation. Their oxidation can be initiated by heme iron of red meat leading to the formation of 4-hydroxy-2-nonenal (4-HNE), a cytotoxic aldehyde. An increased 4-HNE production is implicated in endothelial dysfunction and atherosclerosis. By contrast, a diet rich in proanthocyanidins reduces oxidative stress and arterial diseases. This study evaluates the effects of a WD on vascular integrity in ApolipoproteinE (ApoE-/- ) mice and the protective capacity of apple extract and puree rich in antioxidant proanthocyanidins.METHODS AND RESULTS:ApoE-/- mice are fed during 12 weeks with a WD with or without n-6 PUFAs. Moreover, two WD + n-6 PUFAs groups are supplemented with apple puree or phenolic extract. An increase in digestive 4-HNE production associated with a rise in plasmatic 4-HNE and oxidized LDL concentrations is reported. Oxidizable n-6 PUFAs consumption is associated with a worsened endothelial dysfunction and atherosclerosis. Interestingly, supplementations with apple polyphenol extract or puree prevented these impairments while reducing oxidative stress.CONCLUSION:n-6 lipid oxidation during digestion may be a key factor of vascular impairments. Nevertheless, an antioxidant strategy can limit 4-HNE formation during digestion and thus durably protect vascular function.

Background and aims: Prospective epidemiological studies highlighted recently the link between artificial sweeteners (AS) consumption and the risk of developing cardiometabolic diseases. However, underlying mechanisms remain unknown. Thus, the aim of this preliminary study was to characterize, in a healthy rat population, the effect of chronic AS consumption on body composition and vascular function, an early marker for cardiovascular disease. Methods and results: Healthy Wistar rats followed a 10-week standard diet including the consumption of water sweetened or not with a sucralose/acesulfame potassium solution at different concentrations: for moderate consumption at 1 and 2 mg.kg(-1).day(-1), respectively or high intake at 15 and 15 mg.kg(-1).day(-1) for both molecules (acceptable daily intake). Body fat composition has been evaluated and ex vivo aortic vasomotor function has been investigated with a pharmacological approach. Conclusion: Both groups of AS-treated rats showed a significant increase in subcutaneous and perirenal adipose tissue mass storage, without changes in total body mass. However, rats that have consumed AS at Acceptable Daily Intake (ADI) concentration revealed a significant vascular endothelial dysfunction compared to other groups. These results are interesting because they will help to better explain the observed increase in cardiometabolic risk. (C) 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.