Search

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 (1.0 × 10 8 or 1.0 × 10 9 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and SHRs weekly for 4 weeks. Renal cortical tissues isolated from both rat strains were analyzed by trichrome stain and RT-qPCR. AmEVs protect against the development of hypertension in SHRs without a serious adverse reaction. AmEVs increased the expression of vasocontracting Agt and At1ar as well as vasodilating At2r, Mas1 and Nos2 in the kidneys of both strains. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension., (© 2024. The Author(s).)

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. Extracellular vesicles purified from anaerobically cultured Am were characterized by nanoparticle tracking analysis, transmission electron microscopy, and silver stain after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). AmEVs (1.0 × 10 10  log particles/L) or vehicles were added into organ baths to induce vasorelaxation. In addition, AmEVs (1.0 × 10 8 or 1.0 × 10 9 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) weekly for 4 weeks. Peripheral blood mononuclear cells (PBMCs) and splenocytes isolated from both rat strains were analyzed by flow cytometry, RT-qPCR, and western blot. AmEVs affected neither vascular contraction nor endothelial relaxation in thoracic aortas. Moreover, AmEVs protected against the development of hypertension in SHRs without a serious adverse reaction. Additionally, AmEVs increased the population of T regulatory (Treg) cells and tended to reduce proinflammatory cytokines. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension., (© 2024. The Author(s), under exclusive licence to The Japanese Society of 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., Methods and Results: Eight-week-old Dahl salt-sensitive (SS) male rats were divided into two groups and given either tap water (TW) or a 20% fructose solution (HFS) for 4 weeks. Systolic blood pressure was measured using the tail-cuff method. ScRNA-seq analysis was performed on lamina propria cells (LPs) and peripheral blood mononuclear cells (PBMCs) obtained from SS rats subjected to either TW or HFS. The HFS treatment induced hypertension in the SS rats. The analysis revealed 27 clusters in LPs and 28 clusters in PBMCs, allowing for the identification and characterization of various immune cell types within each cluster. Specifically, B cells and follicular helper T (Tfh) cells were prominent in LPs, while B cells and M1 macrophages dominated PBMCs in the HFS group. Moreover, the HFS treatment triggered an increase in the number of B cells in both LPs and PBMCs, accompanied by activation of the interferon pathway., Conclusions: The significant involvement of B cells in intestinal and PBMC responses indicates their pivotal contribution to the development of hypertension. This finding suggests that targeting B cells could be a potential strategy to mitigate high blood pressure in fructose-induced hypertension. Moreover, the simultaneous increase in follicular B cells and Tfh cells in LPs, along with the upregulation of interferon pathway genes in B cells, underscores a potential autoimmune factor contributing to the pathogenesis of fructose-induced hypertension in the intestine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Joo, Kim, Kim, Jang, Tzeng, Lee, Kim and Kim.)

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. Seven-week-old SS and SR rats were fed a chow (CD) or high-salt diet (HSD) for 4 weeks, with weekly measurements of systolic blood pressure. The relaxation response of the aorta rings to the cumulative addition of acetylcholine was measured ex vivo. In these experimental animals, the Th cell polarity (Th17 and T regulatory [Treg]), the expression of Th17- or Treg-related genes, and the enrichment of the transcription factors RORγt and FOXP3 on the target gene promoter regions were determined via flow cytometry, RT-qPCR, and chromatin immunoprecipitation. Hypertonic salt solution induced Th17 and Treg cell differentiation in cultured splenic T cells isolated from SS and SR rats, respectively. HSD induced hypertension, endothelial dysfunction and proinflammatory Th17 cell differentiation only in SS rats. The enrichment of RORγt on the promoter regions of Il17a and Il23r increased their expression only in SS rats. Regardless of HSD, SR rats remained normotensive with Treg polarity, causing high Treg-related gene expressions (Il10, Cd25 and Foxp3). This study demonstrated that Th cell polarity determines salt sensitivity and drives hypertension development. SR rats were protected from HSD-associated hypertension via anti-inflammatory Treg polarity., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

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-sensitive (SS) and Dahl salt-resistant (SR) rats were fed a HFD (60% fat) or a chow diet (CD; 8% fat) for 12 weeks. We measured blood pressure using the tail-cuff method. The paraffin sections of thoracic perivascular adipose tissue (tPVAT) were stained with hematoxylin/eosin and trichrome. The expression of genes in the tPVAT and kidneys were measured by reverse transcription-quantitative polymerase chain reaction. The HFD induced hypertension in SS (p < 0.01) but not SR rats, although it increased body weight gain (p < 0.05) and tPVAT weight (p < 0.01) in both rats. The HFD did not affect the expression of genes related to any of the adipocyte markers in both rats, although SR rats had reduced beige adipocyte marker Tmem26 levels (p < 0.01) and increased anti-inflammatory cytokine adiponectin (p < 0.05) as compared with SS rat. The HFD did not affect the mRNA expression of contractile factors in the tPVAT of SS and SR rats. SR rats are protected against hypertension during diet-induced obesity. This result implies that the genetic trait determining salt sensitivity may also determine fructose and fat sensitivity and that it is associated with the prevention of hypertension.

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. The tail-cuff method was used to measure systolic blood pressure. T cell (Th17 and regulatory T (Treg)) profiling was analyzed by flow cytometry. The expressions of Th17-related interleukin- (IL-) 17A and Treg-related IL-10 were measured by ELISA. Th17 cells isolated from adult SHR were intraperitoneally injected into juvenile recipient SHR and Wistar-Kyoto rats (WKY). SHR exhibited prominent development of hypertension at 15 weeks. The proportion of CD4 + IL-17A + (Th17) cells among Th cells increased whereas the proportion of CD4 + FoxP3 + (Treg) cells decreased in SHR, as compared to WKY. The serum levels of IL-17A increased gradually with aging in SHR, but the serum levels of IL-10 did not. The serum levels of IL-17A and IL-10 seemed to be well related to the proportion of Th17 cells and Treg cells, respectively. Injection of Th17 cells isolated from adult SHR accelerates the development of hypertension in juvenile SHR but not in juvenile WKY though it increased the proportion of Th17 cells in juvenile recipient WKY and SHR. The transfer of Th17 cells from adult SHR accelerates the development of hypertension in juvenile SHR. These results implicate that the hypertension in SHR is ascribed to activation of Th17 cells., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Jee Young Kim et al.)

Objective: To investigate the association between particulate matter (PM2.5) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in hypertensive and non-hypertensive individuals., Methods: Twelve hypertensives and nine non-hypertensives were monitored during a 36-hour period using a repeated-measures panel study design. Personal exposure to PM2.5 was assessed using a real-time continuous monitor. Spot urine samples collected at 12-hour intervals were analyzed for 8-OHdG., Results: Exposure to PM2.5 was associated with a decrease in 8-OHdG in hypertensives compared with an increase in non-hypertensives, after adjusting for age, gender, smoking status, and time of day., Conclusions: The results suggest modification of the association between PM2.5 exposure and urinary 8-OHdG by hypertension status. Antioxidant activity present in antihypertensive medications may play a role or PM2.5 exposure may reduce the capacity to repair DNA damage in hypertensives. These results should be confirmed with further investigation.