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Innate and adaptive immune cells that have been implicated in hypertension pathophysiology. Cells of the innate and adaptive immune system secrete factors including reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ), and cytokines that promote or inhibit hypertension and hypertensive end-organ damage. The role of eosinophils and B cells, which secrete immunoglobulins such as IgG, is still unclear (Created with BioRender.com; Illustration Credit: Ben Smith). IFN-γ indicates interferon γ; IL, interleukin; ILC, innate lymphoid cell; MDSC, myeloid-derived suppressor cell; NLRP3, NOD-like receptor family pyrin domain containing 3; and TNF-α, tumor necrosis factor α. Downloaded from http://ahajournals.org by on April 3, 2021
Source publication
Elevated cardiovascular risk including stroke, heart failure, and heart attack is present even after normalization of blood pressure in patients with hypertension. Underlying immune cell activation is a likely culprit. Although immune cells are important for protection against invading pathogens, their chronic overactivation may lead to tissue dama...
Contexts in source publication
Context 1
... importance of innate immunity in the development of hypertension and its associated end-organ damage has been demonstrated over the last several decades. 75,76 Seminal studies investigated the role of myeloid cells, specifically monocytes, macrophages, and DCs, in antigen presentation and production of proinflammatory cytokines that promote hypertension ( Figure 3). 77-81 Ablation of myelomonocytic cells expressing lysozyme M (LysM iDTR) by low-dose administration of diphtheria toxin completely abrogated the rise of BP in response to a pressor dose of Ang II. ...
Context 2
... cells are classified by their surface markers, cytokine profile, and lineage determining transcription factors, with each subset exhibiting precise functions in health and disease. Major T-cell classes are CD4 + T helper (Th) cells, CD8 + T cytotoxic (Tc) cells, and CD4 − CD8 − T cells, which includes the innate-like gamma delta (γδ) T cells (Figure 3). In response to signals from antigenpresenting cells or other environmental factors including the local cytokine milieu, CD4 + Th cells further differentiate into pro-or anti-inflammatory subtypes including Th1 cells that produce interferon γ (IFN-γ) and respond to intracellular pathogens; Th2 cells that produce IL-4 and IL-5 and are involved in allergic disorders and parasitic infections; Th17 cells that produce IL-17A and IL-21 and are involved in autoimmunity and the response to extracellular pathogens; T follicular helper cells that produce IL-21 and signal to B cells to promote antigen-specific immunoglobulin production; and Tregs that produce IL-10 and suppress immune responses. ...
Citations
... Secondly, in terms of Inflammatory Status, reduced RDW values typically signal decreased systemic inflammation [25]. Chronic inflammation, a major contributor to hypertension, fosters endothelial dysfunction, arterial stiffness, and vascular remodeling [26]. Consequently, diminished inflammation levels correspondingly mitigate the likelihood of hypertension development. ...
The relationship between red cell distribution width (RDW) and hypertension remains a contentious topic, with a lack of large-scale studies focusing on the adults in the United States. This study aimed to investigate the association between RDW and hypertension among US adults from 1999 to 2018. Methods: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. RDW values were obtained from the Laboratory Data’s Complete Blood Count with 5-part Differential—Whole Blood module. Hypertension data were obtained through hypertension questionnaires and blood pressure measurements. Multivariable weighted logistic regression analyses were conducted to assess the association between RDW and hypertension, followed by subgroup and smooth curve analyses. Results: Compared to the non-hypertensive group, the hypertensive group exhibited higher RDW values (13.33±1.38 vs. 12.95±1.27, P <0.001). After adjusting for covariates, weighted multivariable logistic regression analysis revealed a positive correlation between RDW and hypertension prevalence (OR: 1.17, 95% CI 1.13, 1.21, P <0.001). When RDW was included as a categorical variable, participants in the fourth quartile had the highest risk of hypertension (OR: 1.86, 95% CI 1.70, 2.03, P <0.001). Subgroup analysis showed that, except for age, BMI and weak/failing kidneys, gender, race, education level, smoking, alcohol use, congestive heart failure, and stroke did not significantly influence this correlation (all P-values for interaction >0.05).Smooth curve fitting analysis revealed a reverse J-shaped relationship between RDW and hypertension prevalence, with an inflection point at 12.93%. Conclusion: We first explored the relationship between RDW and hypertension among US adults and discovered a reverse J-shaped association, providing further insights into the relationship between blood cell counts and hypertension and offering a new foundation for hypertension prevention and control.
... 70 In hypertensive patients, due to the decreased intestinal barrier function, the inflammation in the body also increases when the concentration of TMAO rises. 71,72 Multiple studies have shown that the level of plasma TMAO is associated with the risk of hypertension and other diseases, and there is a dose-dependent relationship. [73][74][75][76][77] Animal models have demonstrated that specific intestinal microbiota are highly positively correlated with plasma TMA, TMAO levels, and the degree of atherosclerotic lesions, while certain bacterial flora show a negative correlation. ...
Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.
... Reportedly, the immune system can regulate blood pressure and reduce the damage to target organs. Macrophages, T cells, angiotensin II, and cytokines participate in the occurrence and development of hypertension and its complications through immune mechanisms (Madhur et al., 2021). The activation of the inherent and adaptive immune system causes target-organ damage and dysfunction, and evidently, hypertension is related to abnormal immune activation. ...
Background
Smilax glabra Roxb. (named tufuling in Chinese, SGR) has both medicinal and edible value. SGR has obvious pharmacological activity, especially in anti-inflammation and treating immune system diseases. This study investigated differential protein expression and its relationship with immune infiltration in hypertension treated with SGR using proteomics and bioinformatics.
Methods
N-Nitro L-arginine methyl ester (L-NAME) was used to replicate the hypertension model, with SGR administered by gavage for 4 weeks, and the systolic and diastolic blood pressure in each group of rats was measured using the tail-cuff method every 7 days. Furthermore, enzyme-linked immunosorbent assay (ELISA) was used to determine the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) expressions in each group, followed by the detection of protein expression in rat liver samples using the tandem mass tag (TMT) technique. Additionally, hub targets were output using Cytoscape 3.9.1 software, and ALDH2 expression in the liver and serum in each group of rats was detected by ELISA. Moreover, R4.3.0 software was used to evaluate the relationship between acetaldehyde dehydrogenase 2 (ALDH2) and immune cells, and ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) was performed to identify the components of SGR. Furthermore, the association between components of SGR and ALDH2 was analyzed with molecular docking and LigPlot1.4.5 software.
Results
Compared with the model group (L-NAME), SGR at high and medium doses reduced systolic and diastolic blood pressure while reducing TC, TG, and LDL-C levels and increasing HDL-C levels in hypertensive rats (p < 0.05). Moreover, 92 differentially expressed proteins (DEPs) were identified using TMT. These DEPs participated in peroxisome functioning, fatty acid degradation, and other signaling pathways, with ALDH2 being the core target and correlated with various immune cells. In addition, 18 components were determined in SGR, with 8 compounds binding to ALDH2. Molecular docking was performed to confirm that SGR played a role in hypertension based on the combined action of multiple components.
Conclusion
In conclusion, SGR has an antihypertensive effect on L-NAME-induced hypertension, with ALDH2 as its hub target. SGR may regulate neutrophil, regulatory T cell, and other cells’ infiltration by targeting ALDH2, thereby contributing to the treatment of hypertension.
... [40][41][42] While there is exciting ongoing research on the contributions of the immune system to hypertension, most of these studies do not currently consider the bidirectional alliance between the microbiota and the host immune system. [43][44][45][46][47] One group of studies to consider this relationship demonstrates that dietary salt alters the microbiota, including reducing gut lactobacilli. 6,48 In this salt-sensitive model, these shifts in the microbiota were mechanistically linked to elevated host T helper 17 (Th17) cells and hypertension. ...
... [26] It is reported that chronic H pylori infection led to disturbed immune reactions and inflammation, which ultimately contribute to hypertension. [27,28] However, the impact of H pylori infection on hypertension obtained conflicting results. For example, Wan Z et al [29] found the individuals with H pylori infection had a higher prevalence of hypertension(57.5% vs 55.1%, P = .002), ...
Helicobacter pylori (H pylori) infection was common worldwide and previous researches on the correlation between H pylori infection and metabolic abnormality provided inconsistent conclusions. We assessed acute H pylori infection prevalence and the relationship with metabolic abnormality in general Chinese population. Participants attending for the physical examination underwent a carbon-13 urea breath test. For individual, the following data were collected: age, gender, body mass index (BMI), systolic blood pressure, diastolic blood pressure, total protein, albumin, globulin (GLB), total bilirubin, direct bilirubin (DBIL), indirect bilirubin, alanine transaminase, glutamyl transpeptidase, alkaline phosphatase, cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, urea nitrogen, creatinine, uric acid, fasting plasma glucose (FPG), and homocysteine. A total of 29,154 participants were enrolled. The prevalence of acute H pylori infection was 29.79% (8684/29,154). Spearson correlation analysis showed that gender, BMI, ALB, GLB, total bilirubin, DBIL, indirect bilirubin, and FPG were closely related to H pylori infection. Multinomial logistic regressions analysis with stepwise subset selection further identified gender, BMI, ALB, GLB, DBIL, and FPG as independent risk factors for acute H pylori infection. Our results indicated that acute H pylori infection might has a significant impact on metabolic abnormalities, which should be further confirmed.
... Furthermore, despite effective blood pressure management, patients with hypertension still face cardiovascular risks. This underscores the persistence of residual cardiovascular risk, which may be associated with immune cell activation and chronic inflammation 12 . ...
Hypertension is a disease closely related to inflammation, and the systemic immunity-inflammation index (SII) is a new and easily detectable inflammatory marker. We aimed to investigate the association between SII and hypertension risk in a adult population in the US. We utilized data from the National Health and Nutrition Examination Survey spanning from 1999 to 2018, incorporating comprehensive information from adults reporting hypertension. This included details on blood pressure monitoring, complete blood cell counts, and standard biochemical results. The SII was computed as the platelet count multiplied by the neutrophil count divided by the lymphocyte count. We employed a weighted multivariate logistic regression model to examine the correlation between SII and hypertension. Subgroup analyses were conducted to explore potential influencing factors. Furthermore, smooth curve fitting and two-piecewise logistic regression analysis were employed to describe non-linear relationships and identify inflection points. This population-based study involved 44,070 adults aged 20–85 years. Following Ln-transformation of the SII, multivariable logistic regression revealed that, in a fully adjusted model, participants in the highest quartile of Ln(SII) had a 12% increased risk of hypertension compared to those in the lowest quartile, which was statistically significant (OR:1.12; 95% CI 1.01, 1.24; P < 0.001), with a P for trend = 0.019. Subgroup analysis indicated no significant interactions between Ln(SII) and specific subgroups except for the body mass index subgroup (all P for interaction > 0.05). Additionally, the association between Ln(SII) and hypertension displayed a U-shaped curve, with an inflection point at 5.89 (1000 cells/μl). Based on this research result, we found a U-shaped correlation between elevated SII levels and hypertension risk in American adults, with a inflection point of 5.89 (1000 cells)/μl). To validate these findings, larger scale prospective surveys are needed to support the results of this study and investigate potential mechanisms.
... Previous data from both animal and human studies have demonstrated the critical role of T cells in hypertension. 23,24 The activated T cells infiltrate tissues and produce cytokines leading to hypertension. 25 The infiltration of peripheral T cells into the central nervous system is one of the important mechanisms underlying neuroinflammation involved in the development of hypertension. ...
Objectives: The up-regulation of proinflammatory cytokines in the hypothalamic paraventricular nucleus (PVN) is well demonstrated to be involved in the development of neurogenic hypertension, including stress-induced hypertension (SIH). IL-17A has been found to be increased in the PVN of several hypertensive animal models and has been shown to play a key role in the development of hypertension. Although IL-36γ was found to be expressed in spinal neurons, its role in hypertension remains elusive. Here, we investigated the co-expression of IL-17 receptor A (IL-17RA) and IL-36γ in the PVN cells of SIH rats. Methods: The electric foot shock combined with buzzer noise stressors were used to make hypertensive rat model. The immunochemical staining or immunofluorescence staining was used to reveal cells as requested. The Western blot was used to detect the related protein levels. Results and Conclusion: In the PVN of the SIH rats, the number of CD3⁺CD4⁺ T cells was significantly increased by the immunochemical staining. Additionally, the protein levels of RORγt and IL-17A were significantly upregulated by Western blot, confirming the infiltration of CD4⁺ T cells and differentiation into Th17 cells in the PVN of SIH rats. Immunofluorescence staining revealed abundant expression of IL-17RA in PVN neurons, with relatively less expression in astrocytes or microglia. Furthermore, IL-36γ positive cells and protein expression of IL-36R were significantly increased. Notably, this study demonstrates for the first time that most IL-36γ cells were strongly colocalized with IL-17RA positive cells in the PVN of SIH rats, and the colocalized cells were significantly higher in SIH rats. This suggests that IL-17A secreted by infiltrated Th17 cells may stimulate PVN neurons to produce IL-36γ via IL-17RA, indicating that the combination of IL-17 and IL-36γ might produce strong pro-inflammatory effects in the PVN of SIH rats.
... The process of inflammation plays a crucial role in eliminating harmful factors and repairing tissue damage. However, if inflammation persists, it can potentially lead to the development of various chronic diseases, including hypertension [7]. In studies focused on CVDs, inflammatory markers such as C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-alpha (TNF-α) are linked to poor prognosis in people with hypertension by impairing endothelial function and promoting atherosclerosis [8,9]. ...
Background and objective
Hypertension affects over a billion people worldwide and is often associated with poor prognoses. The neutrophil-to-lymphocyte ratio (NLR) has become a significant marker, showing a connection to adverse outcomes in cardiovascular diseases (CVDs). The objective of this study is to examine the relationship between the NLR and outcomes in patients with hypertension.
Methods
The study included hypertensive individuals who were surveyed in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. Mortality status was determined using the data from National Death Index (NDI). To investigate the dose-response relationship, restricted cubic spline (RCS) models were used. This study employed adjusted cox proportional hazards regression models to compute hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) for all-cause and cardiovascular mortality. The predictive accuracy of the NLR for survival outcomes was assessed utilizing time-dependent receiver operating characteristic (ROC) curve analysis.
Results
A total of 13,724 participants were included in the final analysis, including 7073 males and 6651 females. The cohort was stratified into higher (>2.0) and lower (≤2.0) NLR groups according to the median value. Over a median follow-up of 64 months, there were 1619 all-cause deaths and 522 cardiovascular deaths among participants. The RCS analysis indicated a non-linear relationship between NLR and the risk of mortality. The adjusted model showed that the group with a higher NLR had a significantly higher risk of all-cause (HR 1.47, 95% CI 1.22–1.77) and cardiovascular mortality (HR 2.08, 95% CI 1.52–2.86). ROC analysis showed that the area under the curves (AUCs) of 0.692, 0.662, 0.644, and 0.625 for predicting all-cause mortality, and 0.712, 0.692, 0.687, and 0.660 for cardiovascular mortality at 1, 3, 5, and 10 years.
Conclusion
Elevated NLR is associated with increased risk of cardiovascular and all-cause mortality, and NLR may independently predict outcomes in individuals with hypertension.
... IL-6 can also modulate the expression of genes involved in lipid metabolism, insulin sensitivity, and glucose homeostasis (Xu et al. 2018;Kurauti et al. 2017;Shi et al. 2019;Balakrishnan and Thurmond 2022). Therefore, IL-6 may have both beneficial and detrimental effects on blood pressure and hypertension, depending on the context and duration of its action (Xu et al. 2018;Madhur et al. 2021). ...
To examine whether circulating interleukin-6 (IL-6) levels (CirIL6) have a causal effect on blood pressure using Mendelian randomization (MR) methods. We used data from genome-wide association studies (GWAS) of European ancestry to obtain genetic instruments for circulating IL-6 levels and blood pressure measurements. We applied several robust MR methods to estimate the causal effects and to test for heterogeneity and pleiotropy. We found that circulating IL-6 had a significant positive causal effect on systolic blood pressure (SBP) and pulmonary arterial hypertension (PAH), but not on diastolic blood pressure (DBP) or hypertension. We found that as CirIL6 genetically increased, SBP increased using Inverse Variance Weighted (IVW) method (for ukb-b-20175, β = 0.082 with SE = 0.032, P = 0.011; for ukb-a-360, β = 0.075 with SE = 0.031, P = 0.014) and weighted median (WM) method (for ukb-b-20175, β = 0.061 with SE = 0.022, P = 0.006; for ukb-a-360, β = 0.065 with SE = 0.027, P = 0.014). Moreover, CirIL6 may be associated with an increased risk of PAH using WM method (odds ratio (OR) = 15.503, 95% CI, 1.025–234.525, P = 0.048), but not with IVW method. Our study provides novel evidence that circulating IL-6 has a causal role in the development of SBP and PAH, but not DBP or hypertension. These findings suggest that IL-6 may be a potential therapeutic target for preventing or treating cardiovascular diseases and metabolic disorders. However, more studies are needed to confirm the causal effects of IL-6 on blood pressure and to elucidate the underlying mechanisms and pathways.
... Extensive research has shown that both human and animal studies provide evidence supporting the notion that autoimmunity, inflammation and metabolic may contribute to the development of hypertension [4][5][6]. White blood cells and their various subpopulations, as well as platelets, are indispensable constituents of the systemic inflammatory state. Notably, recent studies have highlighted several markers of systemic inflammation in peripheral blood cells, including the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), which are associated with both cardiovascular and non-cardiovascular disorders such as heart failure, sacroiliitis, diabetic nephropathy [7][8][9][10][11][12][13]. ...
Background
We conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and hypertension prevalence. Our aim is to identify potential biomarkers for early detection of hypertension.
Methods
A cross-sectional study with 119664 individuals from the National Health and Nutrition Examination Survey was performed. We investigated the associations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and the prevalence of hypertension.
Results
The prevalence rates of hypertension gradually increased with increasing logSII, logSIRI, and logAISI quartiles. In continuous analyses, each unit increase in logSII, logSIRI, and logAISI was associated with a 20.3%, 20.1%, and 23.7% increased risk of hypertension. Compared to those in the lowest quartiles, the hypertension risks for subjects in the highest logSII, logSIRI, and logAISI quartiles were 1.114-fold,1.143-fold, and 1.186-fold. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and hypertension prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 9%, 16%, and 11% increase in hypertension prevalence.
Conclusion
Our cross-sectional study reveals significant positive correlations between SII, SIRI, and AISI with the prevalence of hypertension.
