Onset Of Hypertension Research Articles

Abstract P193: Adoptive transfer of placental CD4+ T Cells from preeclamptic patients with a history of COVID-19 causes hypertension and cognitive dysfunction postpartum in a pregnant rat model of preeclampsia

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with activated CD4+ T cells, impaired cognitive function, and changes in cerebral blood flow (CBF) autoregulation. Previously, PE women have been shown to develop neurovascular and cardiovascular disorders earlier in life than those that had uneventful pregnancy. COVID-19 (CV) during pregnancy is associated with an increase incidence of the PE phenotype and is also associated with chronic neurovascular and cardiovascular consequences. Previously, we showed adoptive transfer of placental CD4+ T cells from PE women into athymic nude pregnant rats causes a PE phenotype, however we don’t know the role of CD4+ T cells to cause long-term neurovascular or cardiovascular consequences in PE in the presence or absence of a history (Hx) of COVID-19 during pregnancy. Therefore, we hypothesize that CD4+ T cells from PE patients with and without a Hx of CV causes hypertension and neurovascular dysfunction compared to CD4+ T cells from normotensive patients. One million placental CD4+ T cells from Normotensive (NT), CV Hx NT, and PE patients with or without a CV Hx were isolated and injected interperitoneally (i.p.) into pregnant nude athymic rats on gestational day (GD) 12. Dams were allowed to deliver and aged 12-weeks after delivery. At 12-weeks postpartum, blood pressure (MAP) was measured; CBF autoregulation was measured by laser Doppler flowmetry. The Barnes maze and the novel object recognition behavioral assays were used to assess cognitive function 12-weeks postpartum. A two-way ANOVA was used for statistical analysis. At 12-weeks postpartum, MAP increased in CV Hx PE (153±6, n=7, p<0.05) and PE (150±5 mmHg, n=5, p<0.05) compared to CV Hx NT (121±6, n=6) and NT (116±6 mmHg, n=6), respectively. Behavioral analysis showed CV Hx PE and PE exhibited impaired memory and learning (P<0.05) compared to either NT group. Our findings indicate that rat recipients of CD4+ T cells from PE patients in the presence or absence of CV Hx have HTN and cognitive dysfunction in the postpartum period compared to recipients of control CD4 + T cells. These data indicate the importance of CD4+ T cells in long-term consequences of PE and COVID infection during pregnancy.

Abstract P343: Cerebral injury and cognitive performances are correlated with immunoinflammatory markers in hypertensive patients

Immunity and inflammation play a pivotal role in hypertension onset and cardiovascular organ damage. This role has been thoroughly characterized for classical hypertension targets as the kidneys, the heart and the vasculature. Many studies have characterized this in the experimental context, however immunoinflammatory challenges links with brain injury in the clinical context of hypertension are still lacking. In this study we will characterize how immunoinflammatory mediators can be predictors of cerebral injury characterized by advanced neuroimaging in hypertensive patients. Hypertensive patients underwent cerebral MRI and by advanced neuroimaging we characterized the microstructural injury by DTI fiber tracking. We administered the Montreal Cognitive Assessment to evaluate cognitive function, measured circulating C-reactive protein (hs-CRP) and counted circulating white blood cells (WBC). We found a large cluster of white matter tracts whose integrity parameters were associated with immunoinflammatory biomarkers (Figure A). In particular, a cluster of tracts of the limbic system and encompassing the corpus callosum show a correlation between their loss of integrity and hs-CRP levels. Another cluster of associative tracts spanning the temporal lobe show association between their loss of integrity and the WBC. Finally, the Frontal Aslant and the Uncinate Fasciculus show association with both immunoinflammatory markers (Figure B). In this study we performed advanced neuroimaging analyses to characterize the interplay between immunoinflammatory risk and cerebral alterations in hypertensives. Furthermore, our previous work identified that white matter damage in the Forceps Minor and Superior Longitudinal Fasciculus was a typical trait of hypertensive patients and associated to loss of cognitive functions. Our data further show the inflammatory risk association with worse cognitive functions, suggesting a clinical relevance in terms of damage evidenced by advanced MRI in hypertensive patients.

Abstract P205: Single-nucleus Sequencing Reveals Endothelial Cell-specific Dysregulation in the Kidney in Multiple Models of Hypertension

The kidney plays a crucial role in the onset and progression of hypertension. To investigate the roles of different renal cell types in hypertension, we applied single-nucleus sequencing and spatial transcriptome sequencing to kidney samples from three well-established hypertension models: C57BL/6 mice treated with Ang II, the Dahl salt-sensitive (SS) rat on high-salt diets, and the spontaneously hypertensive rat (SHR), along with their respective controls including Sprague-Dawley (SD) and Wistar Kyoto (WKY) rats. Our dataset comprised 179,637 nuclei from 24 samples across 12 experimental conditions, identifying 17 major cell types including various epithelial cells, endothelial cells, vascular smooth muscle cells, fibroblasts, and immune cells. At baseline, differentially expressed genes between the SS and SD groups were specifically enriched in endothelial cell pathways related to vascular development. This included expression deficiencies in genes involved in angiogenesis in SS rats, such as Arhgap24 and Nox4. Compensatory expression changes in these genes were observed in the SS rats after a high-salt diet and in 26-week-old SHR, but not in their respective controls. These genes were also associated with multiple blood pressure-associated single-nucleotide polymorphisms (SNPs). Furthermore, changes in endothelial cell communication were most prominent upon stimuli, with impaired PTPRM (Protein Tyrosine Phosphatase Receptor Type M) signaling being a robust feature in hypertension models, involving angiogenic endothelial cells in the SS model and proliferating capillary endothelial cells in the SHR model. Our study highlights the critical role of renal endothelial cell angiogenic dysfunction in the pathogenesis of hypertension and suggests a link between specific renal endothelial cell subtype dysregulation and hypertension development.

Abstract P231: Self-administration of Remifentanil Induces Endothelial Dysfunction in Thoracic Aorta and Impaired Cavernosal Reactivity of Wistar Rats

Aims: Recent studies have implicated the use of prescription opioids as a risk factor for cardiovascular diseases (CVD), with associations including myocardial infarction, coronary artery disease and vascular deterioration. Further, opioid-dependent patients show increased vascular aging and arterial stiffness when compared to opioid-naïve controls. Our hypothesis was that rats dependent on remifentanil (a fentanyl analog) after a 12-day operant self-administration (SA) study lead to vascular dysfunction in thoracic aorta. Because erectile dysfunction (ED) is associated with arterial stiffness and is positively correlated with its severity, we hypothesized that opioid SA impaired corpus cavernosum (CC) reactivity as well. Methods: Male Wistar rats (12 weeks-old) were implanted with intravenous catheters and learned to lever press (FR1) for remifentanil (1µg/kg/infusion). A separate group of rats received passive yoked infusions of saline administered in synchrony with remifentanil-treated animals to control volumetric vascular effects. Following administration, animals were euthanized, and aorta and CC collected to evaluate function using both pin and strip myographs. Concentration-response curves to phenylephrine (Phe; 10 -11 -10 -4 M), sodium nitroprusside (SNP) and acetylcholine (Ach or SNP; 10 -10 -10 -4 M) were performed to test contractility and endothelium-independent and -dependent relaxation respectively. Results: Remifentanil-treated rats showed rapidly acquired SA behavior, exhibiting robust and selective drug-paired lever pressing when compared to the non-drug paired lever. In contrast, yoked saline-treated controls rarely exhibited lever pressing. Endothelium-dependent relaxation in the aorta was diminished in the remifentanil group (Rmax: Control: 68.7±2.7 vs. Remi: 47.8±3.7%; p<0.05). There were no observed alterations in endothelium-independent relaxation or vascular contraction. However, CC contraction was slightly shifted to the right in remifentanil treated rats (pEC 50 : Control: 6.04±0.09 vs. Remi: 5.66±0.12; p<0.05). No changes were observed in the CC relaxant response. These findings indicate that 12 days of remifentanil administration results in endothelial dysfunction in large arteries and impaired cavernosal reactivity. Long-term exposure may lead to aortic stiffness exacerbating ED severity and increases in pulse-wave velocity in opioid-dependent patients contributing to the onset of hypertension.

P229 INFLUENCE OF ASTHMA ON BLOOD PRESSURE OF CHILDREN AND ADOLESCENTS: THE ASMAVIX PROJECT

Background and Objectives: Asthma is a prevalent disease in children and the chronic inflammatory may affect blood vessel stiffness and blood pressure (BP). Systolic BP increases progressively along the childhood tending to reach stable values at the beginning of adulthood. Higher BP levels in infancy predispose to hypertension development hypertension in adulthood. Our aim was to investigate the influence of asthma on the age-dependent BP increase in children and adolescents. Methods Asthmatic (Asth, n = 166), 7-15 years (67% boys) attending to Public Health Units of Vitória (an industrialized city of the coastal plain of southeastern Brazil) were included. Non-asthmatic children (N-Asth, n =50; 33% boys) living in the neighborhood of Asth were used as controls. Clinic and laboratory exams were performed in an outpatient clinic at the University Hospital. BP was measured with an oscillometric device (Onrom HBP 1100) and large artery stiffness was estimated by carotid-to-femoral pulse wave velocity (cf-PWV; Complior SP-2). The 90th percentile of systolic or diastolic BP was used to identify high BP considering gender, age, and height. Age-dependent BP increase was determined by linear regression with and without adjustment for covariates (gender and body mass index). Statistical significance was set at p<0.05. Results Asth and N-Asth groups were similar (p>0.05) considering age (11.7 ± 2.3 vs 11.1 ± 2.1 years), body mass index (20.2 ± 4.2 vs 20.3 ± 5.7 kg/m2), systolic (102 ± 11 vs 104 ± 10 mmHg) and diastolic (62 ± 7 vs 63 ±8 mmHg) BP. However, cf-PWV was higher in Asth (48.9 ± 9.0 vs 44.0 ± 9.1 cm/s; p<0.01). The crude age-dependent systolic BP increase was 34% higher in the Asth group (1.74 mmHg/year; 95%CL 1.06;2.43 vs 1.37 mmHg/year; 95% CL 0.02;2.72). This difference remained similar after adjusting for gender and body mass index (1.47 mmHg/year; 95%CL 0.80; 2.14 vs 1.10; -0.47;2.67). The percentage of children with elevated BP was higher in the Asth group (10.2% vs 4.0%). Conclusion: The higher stiffness of large arteries seems to accelerate the systolic BP increase along childhood and adolescence and may predispose to an earlier onset of hypertension in adulthood. Acknowledgment: This study was supported with grants from ArcelorMittal, CNPq and Fapes.

Cardiovascular Risk in Rheumatoid Arthritis: Considerations on Assessment and Management.

In the context of holistic therapeutic practices, the cardiovascular risk of patients with rheumatoid arthritis (RA) needs to be addressed as a major factor of compromised disease prognosis and increased mortality. The elevated prevalence of cardiovascular disease (CVD) by more than twofold in RA has been attributed, inter alia, to chronic inflammation exacerbating arterial stiffness, increased onset of hypertension, dyslipidaemia and diabetes mellitus, sedentary lifestyle, and antirheumatic drug complications. CVD risk in RA can be currently assessed by practitioners through accessible adapted calculators, but it remains problematic as their diagnostic accuracy is not superior to calculators designed for the general population. Implementation of guideline-oriented personalised interventions remains the cornerstone for cardiovascular risk management in RA. Remarkably, there is lack of a consortium that brings together different health care providers engaged in the care of patients with RA (e.g., rheumatologists, cardiologists, general practitioners, etc), to guide cardiovascular risk assessment and management. This narrative review aims at providing an overview of current CVD risk assessment and management options, highlighting their pivotal role in the comprehensive treatment of RA patients.

Abstract P105: Comparative Effectiveness between Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors on Mortality: a Nationwide, Population-based, Prospective Cohort Study in China

Background: Contemporary evidence comparing the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) versus angiotensin II receptor blockers (ARBs) on long-term outcomes in patients with hypertension is sparse and inconsistent. The aim is to compare the effectiveness of ACEI monotherapy versus ARB monotherapy on all-cause death and cardiovascular death. Methods: Based on a nationwide, population-based prospective cohort project, which covered 318 study sites from 2014 to 2021 in China. Detailed information was collected by questionnaire, physical measurement, and blood test. Participants aged 35-75 years with hypertension and taking ACEI or ARB monotherapy once daily, and with good medication adherence at baseline were included. Information on mortality was followed up until 31 December 2021. Stabilized inverse probability treatment weighting (IPTW) was applied to compare the effectiveness. Results: 68 771 (49326 ARB, 19445 ACEI) participants were finally included, with a mean age of 59.9±8.3 years and 40.2% being female. During a median follow-up time of 44 months, 785 cardiovascular deaths and 1657 deaths were recorded. Compared with ACEI monotherapy, ARB monotherapy was associated with a quarter relative risk reduction of cardiovascular death (IPTW rates: 0.95 % Vs 1.43%, HR =0.73 [ 95%CI , 0.62-0.87]) and one-fifth relative risk reduction of all-cause death (IPTW rates: 2.13% Vs 2.84%, HR =0.80 [ 95%CI , 0.71-0.89]). These differences remained consistent after further adjusting for blood pressure and with differences more pronounced in patients with controlled and newly onset hypertension. Sensitive analysis and subgroup analysis yielded consistent results. Conclusions: Attention should be paid that ARB can be preferred to ACEI in patients with hypertension in terms of long-term health outcomes. Funding: This work was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Science (2021-I2M-1-011), and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4, NCRCSZ-2023-016). Keywords: Hypertension, Angiotensin receptor blocker, Angiotensin-converting enzyme inhibitor, Mortality, Comparative effectiveness

P043 PREACH IMPLEMENTATION PROJECT A SOCIO-ECOLOGICAL FRAMEWORK FOR HYPERTENSION IN PAKISTAN

Background: Worldwide hypertension prevalence is projected to reach 1.56 billion by 2025, affecting 29% of the global population according to the WHO1. It contributes to 7.5 million deaths, 3.7% of total disability-adjusted life years (DALYs) and is responsible for causing stroke in 54% of hypertensives2,3. Pakistan has a prevalence of 43% hypertension with merely 12.5% of controlled hypertensives4,5. There is a pressing need for a national level intervention through uniform clinical approaches for optimum hypertension prevention, treatment and control6, 7. Through PREACH project, we prioritize primary care physicians as first-line responders and are training them on standardized hypertension guidelines to alleviate the burden from tertiary care hospitals. To detect new onset hypertension the project also incorporates early surveillance and community level screenings. Objectives: • To build capacity of practitioners on standardized guidelines endorsed by health ministry, PCS (Pakistan Cardiac Society) & PHL (Pakistan Hypertension League) • To raise community awareness, to screen and develop self-referral pathways to specialty care • To develop a robust national hypertension registry • To include hypertension in essential primary healthcare packages Methodology: Hypertension guidelines are developed. Accredited national certified workforce of more than 14,000 general practitioners (GPs) will be built through guidelines trainings via train the trainer model. Impact assessment studies will be done to assess training effectiveness and implementation at clinics. Community mobilization and awareness campaigns will be run to identify and direct self-referral pathway to an accredited GP. Development of national hypertension registry as a centralized system for data collection to report actual disease burden. Ministry of health will be advocated to prioritize hypertension management via multi-sectoral collaboration i.e. medical societies, academic, non-profit and private-sector for incorporations into annual development programs. Results \Conclusion: We aim to create an impact in the lives of 4.3 million beneficiaries (anti-hypertensive naïve hypertensive patients of Pakistan) by increasing self-referral of hypertensive cases to specialists through PREACH implementation project at all healthcare service delivery levels.

Plasma exchange-sensitive syncytial glomerulopathy in a kidney transplant patient.

Microvascular inflammation (MVI), defined as the presence of glomerulitis and/or peritubular capillaritis, is the key histological lesion of anti-HLA donor-specific antibodies (DSA)-related antibody mediated rejection, but recently other possible mechanisms of MVI have emerged. However, except for peritubular capillary C4d deposition that is more frequently observed in the presence of anti-HLA-DSA, histological features are similar regardless of MVI origin. Therefore, accurately describing patterns of MVI may help differentiate etiologies and drive therapeutic choices. We describe the case of a kidney transplant recipient (primary nephropathy: autosomal dominant polycystic kidney disease) who underwent kidney biopsy for worsening renal function and new onset hypertension. Histologic findings showed severe microvascular inflammation with intense glomerulitis and presence of intracapillary multinucleated cells, positive on immunostaining for endothelial marker ETS-related gene (ERG). Focal intense peritubular capillaritis and early glomerular basement membrane reduplication, C4d negative, were observed, consistent with early chronic active ABMR. HLA-DSA were absent, but high level of anti-angiotensin II type-1 receptor (AT1R) antibodies (Ab) were detected (78 U/L, normal levels < 10 U/L). Two subsequent biopsies showed intense microvascular inflammation with diffuse peritubular capillaritis, and multinucleated, ERG-positive, endothelial cells were still seen in glomerular capillary loops. The patient was started on angiotensin receptor blockers (ARBs) and plasma exchange (PEX) sessions obtaining normalization of blood pressure and AT1R Ab and proteinuria reduction, but, after subsequent liver transplant, rituximab therapy failed to maintain remission and the patient remained PEX-dependent.

A novel mouse model recapitulates the effects of rs2254524 variant in the lanosterol synthase gene on salt sensitivity and organ damage.

The blood pressure (BP) response to salt intake (salt sensitivity) shows great variability among individuals and is more frequent in hypertensive patients. Elevated levels of the steroid hormone Endogenous Ouabain (EO) are associated with hypertension (HT) and salt sensitivity. The lanosterol synthase gene ( LSS ) plays a key role in the biosynthesis of steroids and its rs2254524 variant (Val642Leu) is linked to salt sensitivity in humans. This study aims to investigate the pathophysiological significance of the Lss missense variation in a new knock-in mouse model of salt-sensitive HT onset. We generated a mouse model carrying the murine homolog (Val643Leu) of the human LSS variant. C57BL/6N LssV643L/V643L mice were fed different NaCl diets (low-salt, LSD; normal-salt, NSD; high-salt, HSD) and were characterized at functional, histological, and molecular levels. At baseline, mutant mice showed an enlarged kidney compared to the wild-type (WT) counterpart, but the Lss V643L variant did not affect EO biosynthesis nor systolic BP at 3 and 12 months. In HSD, we observed an increased systolic BP only in 12-month-old LssV643L/V643L mice, compared to NSD. Moreover, only the HSD LssV643L/V643L mice showed cardiac hypertrophy and a higher incidence of cardiac fibrosis compared to WT at 12 months. Finally, the Lss mRNA level was differentially regulated by HSD in the adrenal gland, liver, and heart of LssV643L/V643L mice compared to WT. The novel Lss mouse model resembles the salt-sensitive HT phenotype observed in hypertensive patients and provides a good model of salt-sensitive HT and HT-mediated organ damage.

Puerarin Alleviates Blood Pressure via Inhibition of ROS/TLR4/NLRP3 Inflammasome Signaling Pathway in the Hypothalamic Paraventricular Nucleus of Salt-Induced Prehypertensive Rats.

Puerarin is an isoflavone compound isolated from the roots of a leguminous plant, the wild kudzu. Various functional activities of this compound in multiple diseases have been reported. However, the effect and mechanism of puerarin in improving blood pressure remain non-elucidated. The current study was designed to assess the preventive effects of puerarin on the onset and progression of hypertension and to verify the hypothesis that puerarin alleviates blood pressure by inhibiting the ROS/TLR4/NLRP3 inflammasome signaling pathway in the hypothalamic paraventricular nucleus (PVN) of salt-induced prehypertensive rats. Male Dahl salt-sensitive rats were fed low NaCl salt (3% in drinking water) for the control (NS) group or 8% (HS) to induce prehypertension. Each batch was divided into two group and treated by bilateral PVN microinjection with either artificial cerebrospinal fluid or puerarin through a micro-osmotic pump for 6 weeks. The mean arterial pressure (MAP) was recorded, and samples were collected and analyzed. We concluded that puerarin significantly prevented the elevation of blood pressure and effectively alleviated the increase in heart rate caused by high salt. Norepinephrine (NE) in the plasma of salt-induced prehypertensive rats also decreased upon puerarin chronic infusion. Additionally, analysis of the PVN sample revealed that puerarin pretreatment decreased the positive cells and gene level of TLR4 (Toll-like receptor 4), NLRP3, Caspase-1 p10, NOX2, MyD88, NOX4, and proinflammatory cytokines in the PVN. Puerarin pretreatment also decreased NF-κBp65 activity, inhibited oxidative stress, and alleviated inflammatory responses in the PVN. We conclude that puerarin alleviated blood pressure via inhibition of the ROS/TLR4/NLRP3 inflammasome signaling pathway in the PVN, suggesting the therapeutic potential of puerarin in the prevention of hypertension.

Coarctation of aorta presenting as systemic hypertension in a young adult: A case report

A 33-year-old male who was under investigation for young onset hypertension for nine years had weak lower limb pulse and radio femoral delay on examination. Transthoracic echocardiogram revealed a bicuspid aortic valve, and a CT aortogram detected coarctation of the aorta at the junction of the aortic arch and descending thoracic aorta.Coarctation of the aorta is a rare secondary cause of hypertension in young. Symptoms of presentation may vary depending on the site and severity of coarctation. But the commonest presentation is hypertension in the upper extremity of the body. It could be associated with structural heart disease; the commonest is the bicuspid aortic valve. Treatment options for coarctation of the aorta include balloon angioplasty and surgical repair. Lifelong follow-up is needed in both treatment modalities, even after successful correction.

Unique intestinal microflora and metabolic profile in different stages of hypertension reveal potential biomarkers for early diagnosis and prognosis.

Introduction. Hypertension is the most prevalent chronic disease and a major risk factor for cardiovascular and cerebrovascular diseases.Gap statement. However, there has been no substantial breakthrough in aetiology, new drug targets, and drug development of hypertension in recent 50 years.Research aim. Therefore, this study was to screen unique intestinal microbiome and serum metabolic biomarkers which can early diagnose and track the prognosis of hypertension patients in different periods, and analyse its underlying mechanisms and functions.Methods. Four groups of stool and serum samples, including healthy controls (HCs), prehypertension (PHT), hypertension (HT), and hypertension-related complications (HTC), were collected. Microbial diversity assessed using 16S rRNA sequencing. The metabolites in serum samples were detected through LC-MS/MS analysis.Results. The composition of gut microbiota in patients exhibited dissimilarities compared to that in healthy subjects, which was distinguished by Prevotella, Slackia, Enterococcus, Bifidobacterium, and Lactobacillales may be potential markers for tracking the progression of hypertension, and Bifidobacterium, Butyricimonas, Adlercreutzia, Faecalibacterium, Lactobacillus, Ruminococcus, Clostridium, and Acidaminococcus demonstrated diagnostic value. Meanwhile, tracking the dynamic changes of deoxycholic acid, 4-oxododecanedioic acid, and l-arginine can serve as biomarkers for early diagnosis, and investigation into the mechanism by which the intestinal microbiome influences the onset and progression of hypertension. In terms of pathogenesis, the findings revealed that Bifidobacterium may caused the changes of AST, indirect bilirubin, ALT, triglyceride and uric acid by affecting metabolites cis-7-hexadecenoic acid methyl ester and N1-acetylspermidine. Additionally, Coprococcus may cause changes in albumin through the influence of androsterone enanthate.Conclusions. These findings highlight that the unique intestinal microbiome and serum metabolic profile in different periods of hypertension will provide valuable insight for timely diagnosis and prognosis tracking in hypertension patients with promising clinical applications.

Genome-Wide Methylation Analysis Reveals a KCNK3-Prominent Causal Cascade on Hypertension.

Despite advances in understanding hypertension's genetic structure, how noncoding genetic variants influence it remains unclear. Studying their interaction with DNA methylation is crucial to deciphering this complex disease's genetic mechanisms. We investigated the genetic and epigenetic interplay in hypertension using whole-genome bisulfite sequencing. Methylation profiling in 918 males revealed allele-specific methylation and methylation quantitative trait loci. We engineered rs1275988T/C mutant mice using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9), bred them for homozygosity, and subjected them to a high-salt diet. Telemetry captured their cardiovascular metrics. Protein-DNA interactions were elucidated using DNA pull-downs, mass spectrometry, and Western blots. A wire myograph assessed vascular function, and analysis of the Kcnk3 gene methylation highlighted the mutation's role in hypertension. We discovered that DNA methylation-associated genetic effects, especially in non-cytosine-phosphate-guanine (non-CpG) island and noncoding distal regulatory regions, significantly contribute to hypertension predisposition. We identified distinct methylation quantitative trait locus patterns in the hypertensive population and observed that the onset of hypertension is influenced by the transmission of genetic effects through the demethylation process. By evidence-driven prioritization and in vivo experiments, we unearthed rs1275988 in a cell type-specific enhancer as a notable hypertension causal variant, intensifying hypertension through the modulation of local DNA methylation and consequential alterations in Kcnk3 gene expression and vascular remodeling. When exposed to a high-salt diet, mice with the rs1275988C/C genotype exhibited exacerbated hypertension and significant vascular remodeling, underscored by increased aortic wall thickness. The C allele of rs1275988 was associated with elevated DNA methylation levels, driving down the expression of the Kcnk3 gene by attenuating Nr2f2 (nuclear receptor subfamily 2 group F member 2) binding at the enhancer locus. Our research reveals new insights into the complex interplay between genetic variations and DNA methylation in hypertension. We underscore hypomethylation's potential in hypertension onset and identify rs1275988 as a causal variant in vascular remodeling. This work advances our understanding of hypertension's molecular mechanisms and encourages personalized health care strategies.

Primary Hypertension in Children and Adolescents

The incidence of primary hypertension is on the rise in the pediatric population, with an approximate prevalence ranging from 3% to 5%. The most significant risk factors for the onset and development of primary hypertension are well-known, and some of them are preventable, including increased salt consumption and obesity. Connected with metabolic risk factors, elevated blood pressure in childhood is carried into adulthood. Primary hypertension is associated with attenuated vascular responses to various physiological stimuli in both peripheral microcirculation and systemic macrocirculation in adults and children. Endothelial dysfunction is one of the most important features of arterial hypertension, together with an increased level of oxidative stress – both determinants significantly contribute to all the pathophysiological changes observed in hypertension. Systemic arterial hypertension has emerged as a prevalent cardiovascular risk factor associated with substantial morbidity and mortality. Hence, the timely identification of individuals with elevated blood pressure and early-life blood pressure management could serve as a crucial strategy to mitigate the risk of cardiovascular disease and mortality in adulthood.

Anthocyanins as natural bioactives with anti-hypertensive and atherosclerotic potential: Health benefits and recent advances

BackgroundHypertension is a highly prevalent chronic metabolic illness affecting individuals of all age groups. Furthermore, it is a significant risk factor for the development of atherosclerosis (AS), as a correlation between hypertension and AS has been observed. However, the effective treatments for either of these disorders appear to be uncommon. MethodsA systematic search of articles published in PubMed, Web of Science, ScienceDirect, Scopus, and Google Scholar databases over the last decade was performed using the following keywords: hypertension, AS, anthocyanins, antioxidants, gut microbes, health benefits, and bioactivity. ResultsThe available research indicates that anthocyanin consumption can achieve antioxidant effects by inducing the activation of intracellular nuclear factor erythroid 2-related factor (Nrf2) and the expression of antioxidant genes. Moreover, previous reports showed that anthocyanins can enhance the human body's ability to fight against inflammation and cancer through the inhibition of inflammatory factors and the regulation of related signaling pathways. They can also protect the blood vessels and nervous system by regulating the production and function of endothelial nitric oxide synthase (eNOS). Gut microorganisms play an important role in various chronic diseases. Our research has also investigated the role of anthocyanins in the metabolism of the gut microbiota, leading to significant breakthroughs. This study not only presents a unique strategy for reducing the risk of cardiovascular diseases (CVDs) without the need for medicine but also provides insights into the development and utilization of intestinal probiotic dietary supplements. ConclusionIn this review, different in vitro and in vivo studies have shown that anthocyanins slow down the onset and progression of hypertension and AS through different mechanisms. In addition, gut microbial metabolites also play a crucial role in diseases through the gut-liver axis.

Depressive symptoms as risk factors for the onset of home hypertension: a prospective cohort study

Depression is comorbid with somatic diseases; however, the relationship between depressive symptoms and hypertension (HT), a risk factor for cardiovascular events, remains unclear. Home blood pressure (BP) is more reproducible and accurately predictive of cardiovascular diseases than office BP. Therefore, we focused on home BP and investigated whether depressive symptoms contributed to the future onset of home HT. This prospective cohort study used data from the Tohoku Medical Megabank Community-Cohort Study (conducted in the Miyagi Prefecture, Japan) and included participants with home normotension (systolic blood pressure (SBP) < 135 mmHg and diastolic blood pressure (DBP) < 85 mmHg). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale-Japanese version at the baseline survey. In the secondary survey, approximately 4 years later, the onset of home HT was evaluated (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg) and was compared in participants with and without depressive symptoms. Of the 3 082 (mean age: 54.2 years; females: 80.9%) participants, 729 (23.7%) had depressive symptoms at the baseline survey. During the 3.5-year follow-up, 124 (17.0%) and 388 (16.5%) participants with and without depressive symptoms, respectively, developed home HT. Multivariable adjusted odds ratios were 1.37 (95% confidence interval (CI): 1.02–1.84), 1.18 (95% CI: 0.86–1.61), and 1.66 (95% CI: 1.17–2.36) for home, morning, and evening HT, respectively. This relationship was consistent in the subgroup analyses according to age, sex, BP pattern, and drinking habit. Depressive symptoms increased the risk of new-onset home HT, particularly evening HT, among individuals with home normotension.This prospective cohort study revealed that depressive symptoms are risk factors for new-onset home hypertension, particularly evening hypertension among individuals with home normotension. Assessing home blood pressure in individuals with depressive symptoms is important for the prevention of hypertension and concomitant cardiovascular diseases.

Antihypertensive Potential of Pistacia lentiscus var. Chia: Molecular Insights and Therapeutic Implications.

Background: Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from Pistacia lentiscus var. Chia, shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects. However, its anti-hypertensive effects and vascular, circulatory, and renal-related dysfunction, have not been thoroughly investigated. Herein, we aimed to explore the antihypertensive potential of CMG, focusing on vascular and renal endothelium, in vivo. Methods: Two models of hypertension in male rats, induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-high-salt administration, were utilized. CMG was administered at 220 mg/kg daily for four weeks after hypertension onset and blood pressure was measured non-invasively. Whole blood RNA sequencing, metabolomics, real-time PCR, and Western blot analyses of kidney and aorta tissues were additionally performed. Results: CMG significantly lowered systolic, diastolic, and mean blood pressure in both models. RNA sequencing revealed that CMG modulated immunity in the Angiotensin II model and metabolism in the DOCA-HS model. CMG downregulated genes related to oxidative stress and endothelial dysfunction and upregulated endothelial markers such as Vegfa. Metabolomic analysis indicated improved endothelial homeostasis via lysophosphatidylinositol upregulation. Conclusions: CMG emerges as a potent natural antihypertensive therapy, demonstrating beneficial effects on blood pressure and renal endothelial function.

The downregulation of NSUN5 may contribute to preeclampsia†.

Preeclampsia (PE) is a complication of pregnancy characterized by the new onset of hypertension after 20weeks of gestation. The incidence of PE is steadily rising, posing a significant threat to the lives of both the pregnant woman and the fetus. Most studies on PE pathogenesis currently focus on the placenta, but maternal decidualization forms the foundation for placental growth and development. Recent studies have shown that impaired decidualization is also a cause of PE. Decidualization is a process where endometrial stromal cells gradually transform into secretory decidual cells during early pregnancy. While NSUN5 encodes a member of a conserved family of proteins, its role in pregnancy remains unknown. In this study, we conducted experiments and observed a significant downregulation of NSUN5 expression in severe PE decidual tissues compared to those of normal pregnant women. When inducing decidualization in vitro, we found an increase in NSUN5 expression. However, when we used siRNA to knockdown NSUN5 expression, the process of decidualization was prevented. Moreover, we observed a decrease in ATP content during both cell decidualization and after knockdown of NSUN5. Finally, through immunoprecipitation combined with mass spectrometry, we discovered that the protein ATP5B interacts with NSUN5. Furthermore, after knocking down ATP5B using siRNA, we observed impaired decidualization. Moreover, transfection with siRNA to suppress NSUN5 resulted in a decrease in ATP5B expression. These significant findings provide strong evidence that NSUN5 plays a crucial role in decidualization and is closely associated with the development of PE through its interaction with ATP5B.

Peripheral Blood miRNA Expression in Patients with Essential Hypertension in the Han Chinese Population in Hefei, China.

Primary hypertension is a significant risk factor for cardiovascular diseases. However, the pathogenesis of primary hypertension involves multiple biological processes, including the nervous system, circulatory system, endocrine system, and more. Despite extensive research, there is no clear understanding of the regulatory mechanism underlying its pathogenesis. In recent years, miRNAs have gained attention as a regulatory factor capable of modulating the expression of related molecules through gene silencing. Therefore, exploring differentially expressed miRNAs in patients with essential hypertension (EH) may offer a novel approach for future diagnosis and treatment of EH. This study included a total of twenty Han Chinese population samples from Hefei, China. The samples consisted of 10 healthy individuals and 10 patients with EH. Statistical analysis was conducted to analyze the general information of the two-sample groups. High-throughput sequencing and base identification were performed to obtain the original sequencing sequences. These sequences were then annotated using various databases including Rfam, cDNA sequences, species repetitive sequences library, and miRBase database. The number of miRNA species contained in the samples was measured. Next, TPM values were calculated to determine the expression level of each miRNA. The bioinformatics of the differentiated miRNAs were analyzed using the OECloud tool, and RPM values were calculated. Furthermore, the reliability of the expression was analyzed by calculating the area under the Roc curve using the OECloud tools. Statistical analysis revealed no significant differences between the two samples in terms of age distribution, gender composition, smoking history, and alcohol consumption history (P > 0.05). However, there was a notable presence of family genetic history and high BMI in the EH population (P < 0.05). The sequencing results identified a total of 245 miRNAs, out of which 16 miRNAs exhibited differential expression. Among the highly expressed miRNAs were let-7d-5p, miR-101-3p, miR-122-5p, miR-122b-3p, miR-192-5p, and miR-6722-3p. On the other hand, the lowly expressed miRNAs included miR-103a-3p, miR-16-5p, miR-181a-2-3p, miR-200a-3p, miR-200b-3p, miR-200c-3p, miR-221-3p, miR-30d-5p, miR-342-5p, and miR-543. This study initially identified 16 miRNAs that are aberrantly expressed and function in various processes associated with the onset and progression of essential hypertension. These miRNAs have the potential to be targeted for future diagnosis and treatment of EH. However, further samples are required to provide additional support for this study.