Clinical and Experimental Hypertension最新文献

This study investigated the impact of maternal high-fat diet on vascular function and endothelial homeostasis in offspring. We found that offspring exposed to maternal high-fat diet exhibited elevated blood pressure, impaired abdominal aortic vascular function, and endothelial homeostasis imbalance. These changes were accompanied by increased levels of reactive oxygen species (ROS) and upregulation of pro-inflammatory cytokines (including IL-1β, TNF-α, IL-6, and IL-10). Treatment with NLRP3 or IL-1β inhibitors prevented the deterioration in vascular function, reduced endothelial NO production, and inflammation induced by maternal high-fat diet exposure compared to the control group. The findings suggest that during pregnancy, mitigating the vascular impairments in offspring induced by maternal high-fat diet can be achieved by inhibiting the NLRP3/IL-1β pathway.

Objectives: Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension.

Methods: A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network.

Results: During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model.

Conclusions: The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

Objective: To investigate the mechanism by which cinnamaldehyde (CA) alleviates pulmonary arterial hypertension (PAH) through the TLR4/NF-kB/HIF-1a pathway.

Methods: PAH was induced in rats via SU5416 injection and hypoxia. Hemodynamics (RVMP, RVSP, mPAP) were measured. Histological changes were assessed by HE staining, and protein expressions of α-SMA, Col I, TLR4, p-p65, p65, and HIF-1a were detected by western blot. In vitro, hypoxia-induced HPAECs were treated with CA and TLR4 activator RS09TFA. Cell function was assessed by CCK-8, colony formation, and scratch assays, with VE-Cadherin and α-SMA expression analyzed by western blot.

Results: PAH rats showed increased RVMP, RVSP, mPAP, and pulmonary artery thickening. CA significantly alleviated lung damage and reduced α-SMA and Col I expression. TLR4/NF-kB/HIF-1a activation with RS09TFA inhibited CA's effects. In vitro, CA mitigated hypoxia-induced HPAEC dysfunction, restoring VE-Cadherin and α-SMA expression, while RS09TFA blocked these effects.

Conclusion: CA alleviates PAH by inhibiting the TLR4/NF-kB/HIF-1a pathway and suppressing vascular remodeling, suggesting its potential as a therapeutic agent for PAH.

Objective: Contributing factors for the development of heart failure (HF) involve both apolipoprotein B (ApoB) and coronary microvascular dysfunction (CMD). Although ApoB has been linked to diverse cardiovascular risks, its association with CMD remains unclear.

Methods: A total of 145 patients undergoing cardiac single-photon emission computed tomography (SPECT) scan was enrolled into this retrospective study. Based on ApoB serum level, all subjects were classified into three groups (Group 1-3). Myocardial flow reserve (MFR) was calculated using myocardial blood flow (MBF) tested in different contexts.

Results: ApoB serum level was positively correlated to rest MBF but inversely associated with stress MBF and MFR. Following adjustment for covariates, a significant relationship was observed between increased ApoB and decreased MFR. The predictive value of ApoB was test by Receiver Operating Characteristic Curve (ROC) analysis, showing an area under curve (AUC) of 0.87.

Conclusion: The findings indicated that a higher level of ApoB correlated with the severity of CMD.

Pulmonary arterial hypertension (PAH) is one of the most severe complications of systemic lupus erythematosus (SLE) with high mortality and limited treatment options, primarily due to its unclear pathogenesis. This study aims to investigate the role of intermittent hypoxia (IH) in exacerbating pulmonary arterial remodeling in SLE-PAH using MRL/lpr lupus-prone mouse. In this study, twelve female MRL/lpr mice and six female BALB/c mice were exposed to hypoxia for 2 hours daily over 28 days in a hypoxic chamber (FiO₂, 12%). Among them, six MRL/lpr mice received treatment with LW6, a HIF-1α inhibitor. Moreover, six MRL/lpr mice were exposed to normoxia (FiO2, 21%) and served as controls. As a result, IH MRL/lpr mice developed significant PAH, with right ventricular systolic pressure (RVSP) measuring 32.95 ± 2.08 mmHg, significantly higher than the 26.63 ± 2.72 mmHg observed in normoxic MRL/lpr mice (p < .001). Additionally, the right ventricular hypertrophy index (RVHI) and medial wall thickness (MWT) of pulmonary artery markedly elevated in IH MRL/lpr mice. The protein expression level of HIF-1a and P-NFκB were significantly upregulated in the lungs of these mice. However, treatment with LW6 during hypoxia reduced RVSP and alleviated pulmonary arterial remodeling in MRL/lpr mice. Notably, BALB/c mice subjected to 2 hours of daily hypoxia did not exhibit pulmonary arterial remodeling. This study establishes a reproducible SLE-PAH model, demonstrates the critical role of hypoxia in disease progression, and identifies HIF-1α as a potential therapeutic target for managing SLE-PAH.

Background: Hyperuricemia and hypertension are prevalent chronic diseases that often co-occur. While numerous observational studies suggest an association between serum uric acid (SUA) levels and hypertension, the causal nature of this relationship remains unresolved due to confounding and reverse causation. This study systematically investigates the causal association between SUA levels and hypertension risk using Mendelian randomization (MR) methodologies.

Methods: We utilized single nucleotide polymorphisms (SNPs) identified in large-scale genome-wide association studies (GWAS) of European populations as genetic instruments for SUA levels. MR, a genetic epidemiology technique, uses genetic variations as proxies to mimic a randomized controlled trial and minimizing biases from confounding and reverse causation. Systolic and diastolic blood pressure (SBP and DBP) were the primary outcomes of interest. A two-sample MR analysis was conducted to assess the causal relationships, complemented by sensitivity analyses (weighted median, weighted mode, MR-Egger) to ensure result robustness. Findings are expressed as odds ratios (ORs) with 95% confidence intervals (Cis) per one standard deviation (SD) increase in SUA levels.

Results: Our MR analysis identified a significant causal effect of SUA levels on hypertension risk. Specifically, genetically predicted SUA levels were positively associated with SBP (β = 0.136 [0.035-0.238], p < .05) and DBP (β = 0.108 [0.007-0.209], p < .05).Conversely, reverse MR analysis revealed no significant causal effect of SBP (b = 0.058 [ - 9.52E-05-0.116],p = .0504] or DBP (β = 0.016 [ - 0.028-0.059], p > .05] on SUA levels, confirming the unidirectional nature of this association.

Conclusion: This study provides compelling evidence from MR supporting a unidirectional causal link between SUA levels and increased hypertension risk. Unlike prior observational studies, our genetic approach effectively mitigates confounding and reverse causation, offering novel insights into the etiology of hypertension. These findings highlight the clinical importance of managing SUA levels to mitigate hypertension risk. Further research, including randomized controlled trials, is needed to confirm these findings and explore potential therapeutic interventions targeting SUA.

Purpose: Obstructive Sleep Apnea Syndrome (OSAS) is a heterogeneous syndrome and shows different phenotypic, clinical and physiopathological features. The aim of this study was to examine the relationships between OSAS phenotypes and comorbidities and anthropometric measurements and to identify OSAS phenotypes that should be referred for early diagnosis and treatment.

Materials and methods: We retrospectively reviewed 600 patients who underwent polysomnography (PSG) in our sleep center. Seven phenotypes were defined as Simple Snoring (SS)-Control, Mild, Moderate and Severe OSAS, Rem Dependent OSAS (RDO), Position Dependent OSAS (PDO) and Rem+Position dependent OSAS (R+PDO). Demographic data, anthropometric measurements and comorbid diseases of the patients were obtained retrospectively from their files. OSAS phenotypes were compared with comorbidities and anthropometric measurements.

Results: Severe OSAS was the most common phenotype. Oxygen desaturation index (ODI) and anthropometric measurements showed significant differences between phenotypes (p < .001). Hypertension (HT) (43.7%) and ischemic heart disease (CHD) (14.2%) were the most common comorbidities and were most commonly associated with severe OSAS. In logistic regression analysis, neck circumference (NC) and body mass index (BMI) were the anthropometric measures that predicted OSAS phenotypes. NC and BMI predicted severe OSAS, NC predicted PDO and R+PDO, and BMI predicted RDO.

Conclusion: This study revealed that OSAS phenotypes exhibit different clinical and anthropometric characteristics and differ in comorbidity risks. HT was found to be higher in severe OSAS, moderate OSAS and R+PDO, and CHD was higher in severe OSAS and RDO. Our study emphasized the importance of phenotypic characteristics as well as AHI in the management of comorbidities in OSAS.

Objective: Based on Mendelian randomization (MR) methods, this study aims to explore causal associations of uric acid (UA) levels with aortic aneurysms (AAs).

Methods: In this MR study, data on UA levels and gout were extracted from genome-wide association study (GWAS) meta-analysis conducted by UK Biobank (UKB) for European population and the Biobank Japan Project (BBJ) for Asian population. Summary statistics of AAs were obtained from different databases. Inverse variance weighted (IVW), weighted-mode, weighted median, MR-Egger, and MR-PRESSO methods were used to examine the potential causal association of UA with AAs.

Results: The IVW estimates indicated that elevated UA level was associated with higher AAA risk among the European population (OR = 1.315, 95%CI: 1.024-1.689). In the Asian population, the UA level was positively linked to the odds of AA (OR = 1.393, 95%CI: 1.061-1.829). In addition, sensitivity analyses through MR leave-one-out and single SNP effect methods showed that these results were relatively robust.

Conclusions: UA may be a potential risk factor for AAs, indicating that clinicians should focus on serum UA levels among populations with high-risk of AAs. Studies to reveal the true relationship between them and clarify the underlying mechanism are still needed in the future.

Aging-related diseases, which are associated with the senescence of endothelial progenitor cells (EPCs), are consistently accompanied by elevated levels of circulating trimethylamine-N-oxide (TMAO), a marker predictive of poor prognosis. Lycopene (Lyc) deficiency has been demonstrated to be linked to these age-related diseases. The AMPK/SIRT1 pathway plays a pivotal role in cellular senescence. In this study, we hypothesize that lycopene could mitigate TMAO-induced EPCs senescence, with involvement of the AMPK/SIRT1 pathway. EPCs were subjected to treatment with TMAO, Lyc, small interfering RNA targeting AMP-activated protein kinase (siAMPK), or sirtin-1 (siSIRT1). The biological functions of EPCs were evaluated through, CCK-8, transwell and tube formation assays, while their senescence was assessed via SA-β-gal activity assay and Western blotting. ROS generation was measured using dichlorodihydrofluorescein diacetate staining. TMAO-induced suppression of EPCs' functionality was alleviated by Lyc, but this effect was reversed by siAMPK and siSIRT1. TMAO increased SA-β-gal-positive cell number and ROS production, while reducing the expression of AMPK and SIRT1. These effects were attenuated by Lyc. However, the protective effects were diminished by siAMPK and siSIRT1. In conclusion, Lyc ameliorates TMAO-induced EPCs senescence through the AMPK/SIRT1 pathway.