Clinical and Experimental Hypertension最新文献

Background: Atherosclerosis (AS) is a complex cardiovascular disorder driven by endothelial cell dysfunction and immune microenvironment dysregulation. We identified novel endothelial-related diagnostic biomarkers through multi-omics integration and machine learning approaches.

Methods: Single‑cell atlas of AS was constructed from scRNA-seq data using the Seurat. Endothelial cell‑specific co‑expression modules and hub genes were identified via high-dimensional WGCNA (hdWGCNA), and key endothelial‑associated differentially expressed genes (DEGs) were obtained by integrating these modules with differential expression analysis. Diagnostic genes were screened using LASSO regression and SVM-RFE using glmnet and caret packages, respectively. Their correlations with immune cell infiltration were assessed by single-sample GSEA (ssGSEA) and the CIBERSORT algorithm. Finally, the binding capacity of the encoded proteins to potential therapeutic agents was evaluated through drug-target prediction using the Enrichr platform and the DSigDB database, followed by molecular docking simulations.

Results: A total of 66 endothelial cell-associated DEGs were identified, from which four core feature genes (ANXA2, DBN1, ZNF385D, and IL6ST) were screened using machine learning approaches. Immune infiltration analysis revealed a global increase in immune cell infiltration (e.g., activated B cells, T cells, and macrophages) in atherosclerotic lesions, with the four genes showing significant correlations with specific immune subsets, while single-cell data further confirmed T cells, macrophages, and B cells as the predominant cellular components in the plaque microenvironment. Molecular docking results demonstrated strong binding capabilities of ANXA2 with thalidomide and IL6ST with resveratrol, with binding energies of -6.7 kcal/mol and -7.4 kcal/mol, respectively.

Conclusion: Our findings provided new insights for the targeted AS therapy.

Background: Hypertension, or high blood pressure, is a long-lasting condition caused by sustained high blood pressure in the arteries. The increase and decrease of blood pressure is greatly affected by both dietary and physiological factors. Hence, hypertension may pose serious risks of developing multiple disorders, such as heart and vascular disorders and diabetes, since it is usually not detected for a long time, and thus, it can even speed up the development of some diseases.

Objective: To examine how hypertension risk is related to the variants of the genes AGTR1 (rs5186) and CYP11B2 (rs1799998).

Methods: The meta-analysis led us to search PubMed, Embase, ScienceDirect, NCBI, and Google Scholar for studies relevant to our objective. Case‒control analyses that identified a correlation between the mentioned SNPs and hypertension and provided sufficient data for OR (odds ratio) calculation were included. The rigor of the methodology was assessed using the Newcastle‒Ottawa Scale (NOS) and Hardy‒Weinberg equilibrium (HWE).

Results: In total, 10 studies on AGTR1 (rs5186) and 12 on CYP11B2 (rs1799998) were considered. The polymorphism was examined for a correlation with hypertension risk under all genetic models (allelic, dominant, recessive, or overdominant), but no association was observed. Moreover, no significant findings were obtained from the analysis of publication bias and sensitivity testing.

Conclusion: The AGTR1 rs5186 and CYP11B2 rs1799998 polymorphisms did not show a statistically significant association with hypertension predisposition. A comprehensive study would be necessary to delineate the complex genetic landscape of hypertension.

Objective: To evaluate the apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) ratio as a biomarker for coronary heart disease (CHD) and its clinical phenotypes, beyond traditional lipid parameters.

Methods: This single-center, case-control study analyzed 7,277 patients undergoing coronary angiography. Multivariable logistic regression assessed the independent association of the ApoB/ApoA-I ratio with CHD, acute myocardial infarction (AMI), multivessel disease (MVD), and percutaneous coronary intervention (PCI). Predictive performance was evaluated via ROC curve analysis, with prespecified subgroup analyses.

Results: The ApoB/ApoA-I ratio was the strongest independent lipid predictor of CHD (adjusted OR 4.49, 95% CI 1.98-10.19). It significantly predicted severe clinical phenotypes: AMI (OR 1.94, 95% CI 1.44-2.62), MVD (OR 1.67, 95% CI 1.24-2.26), and PCI requirement (OR 1.95, 95% CI 1.43-2.66). The ratio showed significant discriminatory power for all endpoints (AUCs 0.569-0.608). Subgroup analyses revealed markedly stronger associations in males, older adults (≥60 years), and hypertensive patients, but substantially attenuated predictive value in diabetic patients.

Conclusion: The ApoB/ApoA-I ratio is a superior biomarker for CHD risk stratification, particularly for identifying severe disease manifestations and guiding revascularization decisions in specific patient subgroups. Its integration into clinical practice could enable more precise cardiovascular risk management.

Objective: This study examined differences in aldosterone responsiveness to adrenocorticotropic hormone (ACTH) between the unilateral aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) subtypes of primary aldosteronism (PA) and the impacts on vascular function and treatment outcomes.

Methods: This retrospective study enrolled 97 patients with PA (63 with APA and 34 with IHA) who underwent adrenal venous sampling (AVS) with ACTH stimulation. During AVS, baseline and ACTH-stimulated plasma aldosterone concentration (PAC) and cortisol levels were also assessed. Vascular function was assessed by measuring flow-mediated dilation (FMD). APA tissues were analyzed for KCNJ5 mutations.

Results: Among 97 patients with PA, those with APA showed higher baseline and ACTH-stimulated plasma aldosterone concentration levels, which correlated inversely with FMD. In patients with IHA, the logarithmic difference between PAC measurements before and after ACTH stimulation correlated positively with the blood pressure-normalization effect after mineralocorticoid receptor antagonist (MRA) therapy, with a cutoff value of 2.140 for predicting treatment response.

Conclusion: These findings suggest that ACTH-stimulated aldosterone may offer a useful marker for personalized management of PA, particularly in assessing vascular health and guiding MRA treatment.

Objective: To explore the mechanism by which glycyrrhetinic acid (GA) alleviates chronic heart failure (CHF), focusing on NR3C1-mediated regulation of Nrf2 and oxidative stress.

Methods: A CHF rat model was established via transverse aortic constriction and treated with GA or NR3C1 knockdown. Cardiac function, hypertrophy, fibrosis, and oxidative stress markers were evaluated. In vitro, H9c2 cells were treated with isoproterenol to mimic CHF and subjected to GA, Nrf2 inhibitor, or NR3C1 modulation. Gene/protein expression, ROS, GSH, MDA, and mitochondrial membrane potential were assessed. Regulatory interactions between NR3C1 and Nrf2 were examined using luciferase, ChIP-qPCR, and CHX assays.

Results: GA alleviated myocardial hypertrophy and fibrosis in CHF rat models. GA also suppressed oxidative stress in CHF cell models. GA upregulated Nrf2 and its downstream target HO-1 at the protein level. NR3C1 was identified as a key upstream regulator of Nrf2, promoting its protein stability. NR3C1 knockdown decreased Nrf2 and HO-1 protein expression, disrupted mitochondrial membrane potential, and weakened the protective effects of GA against oxidative stress and cardiac dysfunction both in vitro and in vivo.

Conclusion: GA alleviates CHF by enhancing NR3C1-mediated stabilization of Nrf2 and reducing oxidative stress.

Background: Abnormal circadian blood pressure variation, particularly a non-dipper pattern, is associated with increased cardiovascular risk. Naples Prognostic Score (NPS) is a laboratory-based score that reflects the immune-inflammatory and nutritional status. Nevertheless, data regarding the relationship between NPS, circadian blood pressure patterns, and arterial stiffness in patients with newly diagnosed hypertension are limited. This study aimed to evaluate the relationship between blood pressure dipping status, the NPS, and arterial stiffness assessed by pulse wave velocity (PWV).

Methods: This retrospective study included 297 newly diagnosed, untreated hypertensive patients who underwent 24-hour ambulatory blood pressure monitoring. Patients were classified as dipper (n = 145) or non-dipper (n = 152) according to nocturnal blood pressure decline. Laboratory parameters were recorded, NPS was calculated, and PWV was measured using a validated oscillometric device. Multivariate logistic regression analysis was performed to identify factors independently associated with non-dipper hypertension.

Results: Non-dipper patients had significantly higher median NPS values compared with dippers [2 (0-4) vs. 1 (0-4), p < 0.001] and a higher prevalence of high NPS (score 3-4: 42.8% vs. 13.8%, p < 0.001). Median PWV was also significantly higher in the non-dipper group [7.70m/s (4.70-12.90) vs. 7.00m/s (4.40-11.20), p = 0.005]. After adjustment for clinically relevant covariates, both NPS (OR 1.71, 95% CI 1.19-2.47; p = 0.004) and PWV (OR 1.37, 95% CI 1.12-1.68; p = 0.002) were independently associated with non-dipper hypertension.

Conclusion: In patients with newly diagnosed hypertension, a non-dipper blood pressure pattern is independently associated with higher systemic inflammatory burden and increased arterial stiffness. The NPS may serve as a simple and clinically applicable marker for early cardiovascular risk stratification in this population.

Background: This study aimed to evaluate the safety and efficacy of a time-restricted eating (TRE) intervention to reduce blood pressure (BP) in children and adolescents.

Methods: We conducted a 12-month, three-arm cluster-randomized controlled trial in two schools, with classes as the unit of randomization (91 classes). Children and adolescents with elevated BP were allocated to TREa (12-hour eating window with the last meal before 8:00 PM), TREb (12-hour eating window without a fixed last mealtime), or control (no time restriction). A total of 192 participants were enrolled and analyzed under an intention-to-treat framework (64 per group). Follow-up completion (retention) rates were 65.1% (125/192) at 6 months and 59.4% (114/192) at 12 months, corresponding to loss-to-follow-up rates of 34.9% (67/192) and 40.6% (78/192), respectively. Analyses used mixed-effects models accounting for clustering, with multiple imputations as a sensitivity analysis for missing data.

Results: After 12 months of intervention, both the TREa and TREb groups showed significant reductions in BP, with TREa demonstrating the most significant changes. Systolic blood pressure (SBP) decreased significantly in the TREa (-7.03 mmHg, 95%CI, -10.77 to -3.29 mmHg; P < 0.001) and TREb groups (-5.29 mmHg, 95%CI, -9.44 to -1.14 mmHg; P = 0.013). Diastolic blood pressure (DBP) changes in the TREa group were -4.09 mmHg (-6.80 to -1.38 mmHg; P < 0.001), with significantly different compared to the control group (P = 0.006).

Conclusions: A 12-hour eating window, particularly with the last meal completed before 8 PM, may be associated with lower BP over 12 months in children and adolescents with elevated BP; interpretation should consider the cluster design and attrition.

Trial registration: ChiCTR2400090073 (retrospectively registered on 23 September 2024).

Background: Using reliable, simple, and cost-effective tools to identify pre-hypertension (pre-HTN) early is crucial for reducing the risk of cardiovascular disease (CVD). This systematic review and meta-analysis aimed to assess the association between the risk of pre-HTN and non-insulin-based indices.

Methods: A comprehensive literature search was conducted across electronic databases, including PubMed, Web of Science, and Scopus, until January 2025. Cross-sectional studies investigating the relationship between pre-HTN and IR indices were included. Two investigators independently performed study screening, data extraction, and quality assessment. A random-effects model was used to pool effect sizes, with odds ratios (ORs) as the primary measure of effect.

Results: Overall, 15 studies met the inclusion criteria for this systematic review, and 14 were included in the meta-analysis. All were cross-sectional or employed a cross-sectional approach. The results of the random effects model showed that IR indices, including the fasting triglyceride and glucose index-to-body mass index (TyG-BMI), fasting triglyceride and glucose index-to-waist circumference (TyG-WC), triglyceride-to-high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (METS-IR), and fasting triglyceride and glucose index (TyG), increased the odds of pre-HTN significantly (P < 0.05). The diagnostic odds ratios (DORs) were 2.67 (95% CI: 2.39-2.97) for TyG and 3.45 (95% CI: 2.73-4.35) for TyG-BMI.

Conclusions: This meta-analysis reveals that non-insulin-based IR indices are associated with a higher risk of pre-HTN. However, given the cross-sectional design of all included studies, a causal relationship cannot be inferred. As cost-effective and user-friendly tools, they could aid in the early detection and prevention of HTN, but further prospective and longitudinal research is needed to confirm these findings and establish causality.

Hypertensive disorders of pregnancy (HDP) are common and clinically consequential, affecting ~5%-10% of pregnancies and contributing substantially to maternal and perinatal morbidity and mortality. This review summarizes key concepts that inform bedside decision-making, including contemporary classification, major pathophysiologic pathways (placental dysfunction, endothelial injury, and systemic inflammation), and diagnostic criteria to support timely recognition and risk stratification. Clinically, early identification of preeclampsia and prompt management of severe hypertension and acute complications are central to reducing preventable harm. We highlight evidence-based treatment strategies, focusing on blood pressure control, monitoring for maternal-fetal deterioration, and coordinated multidisciplinary care. Beyond pregnancy, women with prior HDP face elevated long-term cardiovascular risk; therefore, structured postpartum follow-up, cardiovascular risk assessment, and preventive interventions are essential. By integrating current guidelines with recent evidence, this article provides practical recommendations to improve short-term maternal-fetal outcomes and long-term cardiovascular health.

Background: Pulmonary arterial hypertension (PAH) is a lethal vascular disorder characterized by irreversible remodeling of the pulmonary arteries, but the systematic role of the integrated stress response (ISR)-related genes (ISR-RGs) in its pathogenesis remains unexplored.

Objective: This study aimed to identify and validate ISR-associated potential biomarkers for PAH using integrative bioinformatics, single-cell transcriptomics, and experimental approaches.

Methods: We analyzed bulk RNA-seq datasets (GSE38267, GSE131793) and a single-cell RNA sequencing (scRNA-seq) dataset (GSE210248) from PAH patients and controls. A total of 529 ISR-RGs were integrated. Differential expression analysis, machine learning, and functional enrichment analyses were employed to identify potential biomarkers. A diagnostic nomogram was constructed and validated. Immune infiltration, regulatory networks, drug-gene interactions, and molecular docking were further investigated. Key cellular mechanisms were elucidated via scRNA-seq, and biomarker expression was validated using Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) and Enzyme-linked immunosorbent assay (ELISA) in clinical whole blood samples.

Results: We identified four ISR-related diagnostic biomarkers: ABCC4, ATM, SERPINH1, and ZBTB40. These genes showed consistent dysregulation in PAH across multiple datasets and were integrated into a nomogram with good predictive performance (hosmer-lemeshow (HL) test P = 0.432). Gene set enrichment analysis (GSEA) revealed their involvement in translation, neutrophil degranulation, and glucocorticoid pathways. The scRNA-seq highlighted their cell-type-specific expression in T cells and monocytes. Molecular docking identified CAMONSERTIB as a potent ATM-targeting drug (binding energy: -10.2 kcal/mol), and its therapeutic effects on pulmonary arterial hypertension were validated through both animal and cellular models. RT-qPCR and Elisa confirmed upregulation of ABCC4 and downregulation of ATM, SERPINH1 and ZBTB40 in PAH patients.

Conclusions: This study identified four novel ISR-related biomarkers for PAH and elucidated their roles in immune infiltration and cellular remodeling. The findings provided new insights into PAH pathogenesis and offered potential tools for diagnosis and targeted therapy.