Single-cell RNA sequencing reveals that a high salt diet increases IL6R-JAK1-STAT3 gene signaling pathway activity in intestinal B cells and Tfh cells of salt-sensitive hypertension animal model.

Although the immune system plays a crucial role in hypertension, its underlying mechanisms remain unclear. While extensive research has explored the gut-immune relationship in various diseases, the role of gut immunity in salt-sensitive (SS) hypertension is not well understood. In this study, we aimed to elucidate the role of gut immunity in the development of SS hypertension by analyzing immune cells in the gut and blood using single-cell RNA sequencing (scRNA-seq).

Wip1 inhibitor CCT007093 alleviates immune exhaustion of lymphocytes via p65 NF-κB and YY1 in chronic hepatitis B virus infection in mice.

Introduction: Prolonged viral infections often lead to lymphocyte exhaustion, marked by heightened inhibitory receptor expression like PD-1, compromising host defense mechanisms. The unexplored potential of chemical checkpoint inhibitors in rejuvenating immune responses prompted our investigation.

Methods: We focused on CCT007093, a Wip1 inhibitor, screened for its distinctive capacity to simultaneously decrease PD-1 and FcγRIIB expression in B cells.

Increased lamina propria B cells play roles in fructose-induced hypertension of Dahl salt-sensitive rats.

Aims: Although the immune system participates in the development of hypertension, the proportional contributions of distinct immune cells remain poorly understood. With the development of transcriptomics, we can profile the transcriptomes of individual immune cells and assess the relative contribution of each immune cell to the development of hypertension. So, we tested the hypothesis that increased lamina propria B cells play roles in fructose-induced hypertension of Dahl salt-sensitive (SS) rats.

Differential gene expression in the kidneys of SHR and WKY rats after intravenous administration of Akkermansia muciniphila-derived extracellular vesicles.

Although Akkermansia muciniphila (Am) plays a beneficial role as a probiotic in the treatment of metabolic syndrome, the mechanisms remain elusive. We tested the hypothesis that Am extracellular vesicles (AmEVs) protect against hypertension through modulation of gene expression in the kidneys of spontaneously hypertensive rats (SHRs). Extracellular vesicles purified from anaerobically cultured Am (1.

Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension.

Akkermansia muciniphila (Am) shows a beneficial role as a probiotic in the treatment of metabolic syndrome. However, the mechanism remains to be elucidated. We tested the hypothesis that Am extracellular vesicles (AmEVs) have a protective effect against hypertension.

Single cell transcriptome analyses reveal the roles of B cells in fructose-induced hypertension.

Rationale: While the immune system plays a crucial role in the development of hypertension, the specific contributions of distinct immune cell populations remain incompletely understood. The emergence of single-cell RNA-sequencing (scRNA-seq) technology enables us to analyze the transcriptomes of individual immune cells and to assess the significance of each immune cell type in hypertension development.

Objective: We aimed to investigate the hypothesis that B cells play a crucial role in the development of fructose-induced hypertension.

Hypertonic Salt Solution Enhances Inflammatory Responses in Cultured Splenic T-Cells from Dahl Salt-Sensitive Rats but Not Dahl Salt-Resistant Rats.

This study aimed to delineate the effect of sodium chloride on the induction of inflammatory responses and the development of hypertension in Dahl salt-sensitive (SS) and salt-resistant (SR) rats. Splenocytes were isolated from the spleens of SS and SR rats, and cultured on anti-CD3-coated plates for 5 days. The cultured splenic T-cells were challenged with a hypertonic salt solution (0, 20, or 40 mM) in the absence or presence of IL-6 (0, 20, or 60 ng/mL), TGF-β (0, 5, or 15 ng/mL), or IL-23 (0, 10, or 30 ng/mL), and analyzed via ELISA, flow cytometry, and immunofluorescence.

T helper cell polarity determines salt sensitivity and hypertension development.

High-salt intake is known to induce pathogenic T helper (Th) 17 cells and hypertension, but contrary to what is known, causes hypertension only in salt-sensitive (SS) individuals. Thus, we hypothesized that Th cell polarity determines salt sensitivity and hypertension development. Cultured splenic T cells from Dahl SS and salt-resistant (SR) rats subjected to hypertonic salt solutions were evaluated via ELISA, flow cytometry, immunocytochemistry and RT-qPCR.

Dahl Salt-Resistant Rat Is Protected against Hypertension during Diet-Induced Obesity.

A high-fat diet (HFD) frequently causes obesity-induced hypertension. Because Dahl salt-resistant rats are protected against hypertension after high-salt or high-fructose intake, it is of interest whether this model also protects against hypertension after diet-induced obesity. We tested the hypothesis that Dahl salt-resistant rat protects against hypertension during diet-induced obesity.

Dahl salt-resistant rats are protected against angiotensin II-induced hypertension.

Angiotensin II is a potent endogenous vasoconstrictor that induces oxidative stress in hypertensive rodent models. Dahl salt-resistant (SR) rats are protected against hypertension after high salt or high fructose intake. However, whether these rats are also protected against angiotensin II-mediated hypertension has not been investigated.

Zinc-dependent histone deacetylases: Potential therapeutic targets for arterial hypertension.

The pathogenesis of hypertension caused by various genetic and environmental factors has not been elucidated. Clinical trials have evaluated various anti-hypertensive drugs with different therapeutic mechanisms. Due to the increasing prevalence of hypertension in the aging population and appearance of adverse effects, novel anti-hypertensive drugs need be developed.

Inhibition of HDACs (Histone Deacetylases) Ameliorates High-Fat Diet-Induced Hypertension Through Restoration of the MsrA (Methionine Sulfoxide Reductase A)/Hydrogen Sulfide Axis.

[Figure: see text].

Maternal high-fructose intake during pregnancy and lactation induces metabolic syndrome in adult offspring.

Background/objectives: Nutritional status and food intake during pregnancy and lactation can affect fetal programming. In the current metabolic syndrome epidemic, high-fructose diets have been strongly implicated. This study investigated the effect of maternal high-fructose intake during pregnancy and lactation on the development of metabolic syndrome in adult offspring.

Transfer of Th17 from Adult Spontaneous Hypertensive Rats Accelerates Development of Hypertension in Juvenile Spontaneous Hypertensive Rats.

Hypertension develops in the recipient rats that are transferred with the activated T helper (Th) 17 cells of the donor rats exposed to high-fructose or high-salt intake. This result suggests that a pathologic Th17 cell plays a role in the development and maintenance of hypertension. Here, we tested the hypothesis that the transfer of Th17 cells from adult spontaneous hypertensive rats (SHR) accelerates the development of hypertension in juvenile SHR.

Ovariectomy, but not orchiectomy, exacerbates metabolic syndrome after maternal high-fructose intake in adult offspring.

High fructose diet is associated with the global metabolic syndrome (MtS) pandemic. MtS develops in early life, depending on prenatal and postnatal nutritional status. We hypothesized that ovariectomy increases the chances of developing MtS in adult offspring following high fructose intake by the mother.

Histone Deacetylase Inhibition Attenuates Aortic Remodeling in Rats under Pressure Overload.

The use of histone deacetylase (HDAC) inhibitor is a novel therapeutic strategy for cardiovascular disease. Studies have shown that many HDAC inhibitors have the ability to reduce the aortic remodeling in various animal models. We hypothesized that the HDAC inhibitor, MGCD0103 (MGCD), attenuates aortic remodeling in rats under pressure overload-induced by transverse aortic constriction (TAC).

Activation of the renin-angiotensin system in high fructose-induced metabolic syndrome.

High fructose intake induces hyperglycemia and hypertension. However, the mechanism by which fructose induces metabolic syndrome is largely unknown. We hypothesized that high fructose intake induces activation of the renin-angiotensin system (RAS), resulting in hypertension and metabolic syndrome.

Maternal high-fructose intake induces hypertension through activating histone codes on the (pro)renin receptor promoter.

High-fructose intake induces hypertension via the renal expression of (pro)renin receptor (PRR) that stimulates the expression of sodium/hydrogen exchanger 3, Na/K/2Cl cotransporter 2, and genes of the intrarenal renin-angiotensin system. We hypothesize that maternal high-fructose intake induces hypertension in subsequent generation offspring through activating histone codes on the PRR promoter. Mice dams were offered 20% fructose solution during pregnancy and lactation, while the subsequent 1st to 4th generation offspring were raised without fructose.

Acute Exposure to Fructose Impairs Endothelium-Dependent Relaxation via Oxidative Stress in Isolated Rat Aortic Rings.

Introduction: Although both glucose and fructose are hexoses, their catabolism is quite different: the catabolism of fructose is initiated by ketohexokinase and is not regulated by negative feedback, which results in oxidative stress.

Objective: We hypothesized that fructose impairs endothelium-dependent relaxation via oxidative stress in rat aortic rings.

Methods: Sprague-Dawley rats were offered 20% fructose solution or tap water for 2 weeks, after which vascular reactivity was measured in isolated aortic rings.

Activated pathogenic Th17 lymphocytes induce hypertension following high-fructose intake in Dahl salt-sensitive but not Dahl salt-resistant rats.

High-salt intake and high-fructose intake are risk factors for hypertension via oxidative stress and inflammation. T helper (Th)17 lymphocytes play an important role in the development of hypertension. Here, we tested the hypothesis that activation of pathogenic Th17 lymphocytes induces hypertension after high-fructose intake in Dahl salt-sensitive (SS) but not Dahl salt-resistant (SR) rats.

Maternal High-Fructose Intake Induces Multigenerational Activation of the Renin-Angiotensin-Aldosterone System.

Although maternal high-fructose intake induces cardiometabolic syndrome in adult offspring, whether it induces hypertension in successive multiple generations has not yet been studied. We hypothesized that maternal high-fructose intake induces multigenerational activation of the renin-angiotensin-aldosterone system. Pregnant mice were offered 20% fructose in drinking water, of which subsequent first to fourth generation offspring were raised without being offered fructose.

Mineralocorticoid receptor blockade attenuates disrupted glutathione-dependent antioxidant defense and elevated endoglin in the hearts of pregnant rats exposed to testosterone.

Elevated testosterone during late pregnancy has been linked to cardiac dysfunction and poor pregnancy outcomes. The role of mineralocorticoid receptor (MR) in testosterone-induced cardiac dysfunction has not been fully elucidated. The study was therefore designed to investigate the role of MR on gestational excess androgen-induced cardiac disrupted glutathione-dependent antioxidant system and elevated endoglin (Eng) linking it with pregnancy outcomes.