Clinical and Experimental Hypertension最新文献

{"title":"Integrated multi-omics analyses identify an RAS-SLC11A2-associated molecular framework linking iron metabolism with PCOS-related cardiometabolic risk.","authors":"Sihan Zhang, Yu Xu, Tingting Cao, Kun Wang, Lina Jia, Jianning Li","doi":"10.1080/10641963.2026.2711737","DOIUrl":"https://doi.org/10.1080/10641963.2026.2711737","url":null,"abstract":"<p><strong>Introduction: </strong>PCOS is a common endocrine disorder with elevated cardiometabolic risk, yet the role of the renin-angiotensin system (RAS)-iron metabolism axis in this comorbidity remains unclear. We explored its underlying mechanisms and evaluated the therapeutic potential of gentiopicroside.</p><p><strong>Methods: </strong>Integrated multi-omics analyses combining transcriptomics, single-cell RNA sequencing, Mendelian randomization, machine learning, molecular docking, and <i>in vitro</i> functional assays were performed to identify shared molecular pathways and therapeutic targets across PCOS, hypertension, NAFLD, and T2DM.</p><p><strong>Results: </strong>SLC11A2 was consistently dysregulated in PCOS transcriptomic datasets, and associated with iron metabolism, inflammatory response and oxidative stress pathways. Genetic analyses validated RAS-related regulation in hypertension susceptibility and revealed shared genetic architecture between PCOS and cardiometabolic traits. Network and single-cell analyses characterized SLC11A2-associated molecular patterns in disease-relevant cell types; machine learning identified disease-classifying molecular signatures. Gentiopicroside alleviated inflammatory and oxidative stress phenotypes, including reduced IL-6 expression and reactive oxygen species accumulation.</p><p><strong>Conclusion: </strong>This study defines an RAS-SLC11A2 molecular framework linking iron metabolism dysregulation to PCOS-related cardiometabolic risk, elucidating the mechanisms connecting ovarian dysfunction, inflammation, oxidative stress and hypertension, and supports gentiopicroside as a promising therapeutic candidate.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2711737"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the safety and effectiveness of catheter-based renal denervation with the symplicity spyral system in patients with resistant hypertension: A single-center experience.","authors":"Regayip Zehir, Cem Doğan, Anıl Avcı, Gökhan Alıcı, Cemalettin Yılmaz, Emrah Bayam, Elnur Alizade, Münevver Sarı, Ahmet Karaduman, Büşra Güvendi Şengör, Mustafa Ferhat Keten, Azmican Kaya, Doğan Şen, Muhammet Mücahit Tiryaki, Mehmet Kaan Kırali","doi":"10.1080/10641963.2026.2617997","DOIUrl":"10.1080/10641963.2026.2617997","url":null,"abstract":"<p><strong>Background: </strong>Renal denervation (RDN) has emerged as a potential therapeutic option for resistant hypertension (HT), which remains a major clinical challenge due to poor blood pressure (BP) control despite optimized pharmacotherapy. This study aimed to assess the safety and effectiveness of catheter-based RDN in resistant hypertension patients, based on our center's experience.</p><p><strong>Methods: </strong>This retrospective, single-center study included 120 patients with resistant HT who were eligible for RDN and underwent the procedure using the Symplicity Spyral system between January 2023 and December 2024. Office systolic and diastolic BP were assessed at baseline and 6 months after RDN. The primary endpoint was the reduction in BP, while secondary endpoints included changes in the number of antihypertensive medications.</p><p><strong>Results: </strong>At 6 months, office systolic BP decreased significantly from 156 ± 7.7 mmHg to 143 ± 3.7 mmHg, while diastolic BP declined from 93.5 ± 5.5 mmHg to 90 ± 3.9 mmHg (both <i>p</i> < 0.001). Median per-patient reductions were 13 mmHg systolic and 3.5 mmHg diastolic. The mean number of antihypertensive medications decreased from 4.88 ± 0.9 to 4.47 ± 1.1 (<i>p</i> < 0.001). Minor adverse events included acute kidney injury in two patients (1.7%) and femoral artery injury in one patient (0.8%).</p><p><strong>Conclusion: </strong>Catheter-based RDN using the Symplicity Spyral system was safe and effective in reducing BP and medication burden in patients with resistant HT. These results support RDN as a potential therapeutic option in appropriately selected patients.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2617997"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adiponectin improves the aortic dissection by inhibiting inflammatory cell infiltration and macrophage pyroptosis.","authors":"Keng Zhong, Libo Zhao, Chengliang Cai, Jianhui Peng, Shangyi Yu, Jiajun Pan, Xuechao Zhang, Yanren Lu, Qing Xue, Guanxin Zhang","doi":"10.1080/10641963.2026.2657354","DOIUrl":"https://doi.org/10.1080/10641963.2026.2657354","url":null,"abstract":"<p><strong>Objective: </strong>Aortic dissection (AD) is a fatal cardiovascular emergency that is predominantly induced by long-term uncontrolled hypertension.</p><p><strong>Materials and methods: </strong>The mouse AD model was established by combining β-aminopropionitrile with angiotensin II. The incidence rate, rupture rate, and survival status of the mice were evaluated. The structural damage of the aorta was observed using tissue staining technology, the extracellular matrix status, and macrophage pyroptosis were evaluated by immunofluorescence staining, the infiltration of inflammatory cells was detected by immunohistochemistry, the expression of pyroptosis-related molecules, and inflammatory factors was analyzed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Cell proliferation was detected by EdU staining, and cell apoptosis was detected by flow cytometry.</p><p><strong>Results: </strong>In the aortic tissues of AD model mice, the expression of APN, and the content of APN in the serum were significantly decreased. APN intervention can alleviate the thickening of the aortic media, rupture of elastic fibers, and degradation of the extracellular matrix. APN inhibits the proliferation, apoptosis, and phenotypic transformation of vascular smooth muscle cells (VSMCs). At the same time, it can inhibit the infiltration of neutrophils and macrophages and the inflammatory response. Underlying mechanism, it was found that APN inhibited NLRP3-mediated pyroptosis by reducing the release of inflammatory factors; this effect was dependent on the phosphorylation activation of AMPKα and APN receptor.</p><p><strong>Conclusion: </strong>APN plays a protective role in AD. Its underlying mechanism is related to the activation of the AMPK pathway, which in turn inhibits macrophage pyroptosis and vascular inflammation. This study offers a new perspective for the pathological mechanism of AD.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2657354"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMPK-dependent maturation of hiPSC-derived cardiomyocytes induced by human cardiac fibroblast exosomes.","authors":"Kele Qin, Xiuneng Li, Xun Wu, Xiaohui Xie, Kun Xiang, Huatao Zhou, Jinfu Yang, Chengming Fan","doi":"10.1080/10641963.2026.2631601","DOIUrl":"10.1080/10641963.2026.2631601","url":null,"abstract":"<p><strong>Background: </strong>Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a promising therapy for ischemic cardiomyopathy, which is often secondary to hypertension but remain functionally immature. We investigated whether exosomes from human cardiac fibroblasts (hc-FB-EXOs) promote hiPSC-CMs maturation and improve their reparative efficacy after myocardial infarction (MI).</p><p><strong>Methods: </strong>hc-FB-EXOs were isolated from cultured fibroblasts. hiPSC-CMs were treated with hc-FB-EXOs or vehicle and assessed for morphology, sarcomeric organization, metabolism, and electrophysiology. RNA sequencing and Western blotting were used to explore mechanisms. In a mouse MI model, left ventricular function, infarct size, wall thickness, and graft density were evaluated after intramyocardial injection of hiPSC-CMs with or without hc-FB-EXOs.</p><p><strong>Results: </strong>hc-FB-EXOs induced adult-like features in hiPSC-CMs, including increased cell size and sarcomere length, fetal-to-adult isoform switching of myosin and troponin, enhanced mitochondrial respiration, and a shift toward fatty acid-based oxidative metabolism. Electrophysiological maturation was evidenced by a higher peak sodium current density, faster upstroke velocity, and more mature action potential and field potential profiles. Transcriptomic and biochemical analyses identified activation of AMP-activated protein kinase (AMPK) signaling, with the modulation of downstream regulators of fatty acid oxidation. <i>In vivo</i>, co-delivery of hc-FB-EXOs with hiPSC-CMs improved the left ventricular ejection fraction, reduced the infarct size, and increased the graft density compared with those of hiPSC-CMs alone.</p><p><strong>Conclusion: </strong>hc-FB-EXOs promote the maturation of hiPSC-CMs via AMPK-mediated metabolic reprogramming and enhance their therapeutic benefit after MI. Cardiac fibroblast-derived exosomes may serve as a practical adjunct to optimize hiPSC-CMs-based therapy for ischemic cardiomyopathy.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2631601"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory mechanisms and targeted drugs in heart failure.","authors":"Huize Han, Jianan Xu, Zhilin Zhou, Congbo Zhong, Hongyu Li, Aidong Liu, Junfeng Cui","doi":"10.1080/10641963.2025.2608225","DOIUrl":"https://doi.org/10.1080/10641963.2025.2608225","url":null,"abstract":"<p><p>Heart failure (HF) is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. Globally, the morbidity and mortality of HF are still on the rise, especially in elderly individuals, and the low 5-year survival rate of HF is a major social and health management problem. The pathogenesis of heart failure involves genetic factors and persistent cardiac inflammation. Genetic factors typically increase a patient's susceptibility to specific diseases. Notably, persistent cardiac inflammation is also a significant contributor to heart failure. Whether it is spontaneous aseptic inflammation of the heart or inflammation caused by infection, both can lead to excessive activation of the immune system, thereby triggering adverse cardiac remodeling. This review focuses on describing the inflammatory/immune activation mechanisms involved in heart failure and explores targeted drugs for inflammatory/immune activation. Additionally, we focused on the NLRP3 inflammasome (a cellular signaling protein complex), whose excessive activation produces large number of inflammatory factors, including IL-1β and IL-18, ultimately leading to persistent inflammation and excessive immune activation in the myocardium, which in turn triggers myocardial cell death and adverse remodeling. We have revealed the pathogenic role of NLRP3 in heart failure, providing a theoretical basis for further research into heart failure.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2608225"},"PeriodicalIF":3.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arachidonic acid intake promotes hypertension and target-organ fibrosis through CYP4A-mediated 20-HETE overproduction: Integrated evidence from human and animal studies.","authors":"Zhongzheng Zhou, Qinghua Fang, Xingyu Li, Chaohong Li, Jing Huang","doi":"10.1080/10641963.2025.2611130","DOIUrl":"10.1080/10641963.2025.2611130","url":null,"abstract":"<p><p>The unregulated use of highly purified arachidonic acid (AA) supplements among Chinese fitness enthusiasts raises concerns about cardiovascular safety. To evaluate these risks, we integrated population-based, genetic, and experimental evidence. Cross-sectional analysis of NHANES data demonstrated a higher risk of hypertension in individuals within the highest AA intake quartile (OR = 1.262, 95% CI: 1.109-1.438, <i>P</i> < 0.001). Two-sample Mendelian randomization confirmed causal effects of AA metabolites, including thromboxane (OR = 1.006, <i>P</i> < 0.001), eicosanoid C20H28O4 (OR = 1.305, <i>P</i> = 0.009), and 20-HETE-related C20H32O3 (OR = 1.290, <i>P</i> = 0.043). Single-cell transcriptomic profiling revealed increased renal expression of CYP4A11 in hypertensive patients, supporting a mechanistic link between AA metabolism and blood pressure regulation. In vivo, Wistar-Kyoto and spontaneously hypertensive rats fed a high-dose AA diet for six weeks exhibited significant elevations in systolic, diastolic, and mean arterial pressure, accompanied by increased renal vascular resistance. Mechanistic analyses showed that AA upregulated CYP4A1 expression and enhanced 20-HETE production without altering thromboxane synthase activity. Histological assessments revealed glomerular edema, tubular injury, and marked cardiac and renal fibrosis in AA-treated animals. Together, these convergent findings indicate that chronic high-dose AA intake promotes hypertension and multiorgan fibrosis via CYP4A/20-HETE activation. These results highlight the translational importance of AA metabolism in cardiovascular disease and underscore the need for regulatory oversight of AA supplements and therapeutic targeting of this pathway.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2611130"},"PeriodicalIF":3.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145905618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemerin - CMKLR1 signaling contributes to immune metabolic dysfunction in salt-sensitive hypertension.","authors":"Ronald McMillan, Mohammad Saleem, Ariel Thorson, Olivia Pierre-Louis, Selam Desta, Lale A Ertuglu, Celestine N Wanjalla, Lindsey Stolze, Quanhu Sheng, Naome Mwesigwa, Annet Kirabo","doi":"10.1080/10641963.2026.2736024","DOIUrl":"10.1080/10641963.2026.2736024","url":null,"abstract":"<p><p>Salt-sensitivity of blood pressure (SSBP) is a significant cardiovascular risk factor, but its underlying immunometabolic mechanisms remain unclear. Chemerin, an adipose-derived inflammatory mediator linked to vascular dysfunction, was studied in 30 hypertensive adults (mean age 53.1 years; 53% female; mean BMI 32.1 kg/m²) during an inpatient salt-sensitivity protocol. Participants underwent salt-loading and salt-depletion phases over three days. Plasma and urine chemerin levels were measured, alongside immune cell phenotyping and transcriptomic profiling using CITE-seq, RNA-seq, and NanoString. Plasma chemerin increased significantly from salt-loading to salt-depletion (100.4 to 125.8 pg/mL; <i>p</i> = 0.008) and was higher in salt-sensitive individuals during depletion (141.2 vs. 108.6 pg/mL; <i>p</i> = 0.02). Plasma chemerin correlated with systolic blood pressure (SBP) during salt depletion (R² = 0.20, <i>p</i> = 0.01), while urinary chemerin increased but did not correlate with SBP. In vitro, high-sodium media suppressed CMKLR1 (chemerin receptor) expression in monocytes (<i>p</i> < 0.01). CITE-seq revealed a 1.8-fold enrichment of CMKLR1 in classical monocytes in salt-resistant individuals compared to salt-sensitive ones, with CMKLR1 inversely correlating with ΔSBP (R² = 0.47, <i>p</i> = 0.03) and ΔMAP (R² = 0.72, <i>p</i> = 0.004). CMKLR1 was linked to glycolytic and oxidative phosphorylation gene upregulation, and its expression in dendritic cells correlated with urinary lactate and fumarate levels. The chemerin-CMKLR1 axis is dysregulated in SSBP, influencing monocyte and dendritic cell metabolism and blood pressure. Chemerin and CMKLR1 may serve as biomarkers and therapeutic targets for salt-sensitive hypertension.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2736024"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FUNDC2 contributes to hypertensive vascular remodeling by regulating mitochondrial dynamics and ferroptosis in perivascular adipose tissue.","authors":"Yuanyuan Jin, Tingting Song, Tingting Jiang, Yongkang Wei, Yijie Bao, Zixuan Zhu, Ruizhe Zhou, Derun Wang, Yong Zhao, Huiying Li, Yu Fu","doi":"10.1080/10641963.2025.2610587","DOIUrl":"https://doi.org/10.1080/10641963.2025.2610587","url":null,"abstract":"<p><strong>Objective: </strong>Perivascular adipose tissue (PVAT) is closely related to the pathogenesis of vascular remodeling in hypertension. The objective of this study was to explore the specific molecular mechanisms underlying the role of PVAT in the onset and progression of hypertensive vascular remodeling.</p><p><strong>Methods: </strong>Thoracic aorta PVAT from male spontaneously hypertensive rats (SHRs) and male Wistar-Kyoto (WKY) rats was used for proteomic analysis, and the differential expression of the identified target proteins was verified by western blotting, immunohistochemistry and transmission electron microscopy (TEM). In vitro, FUN14 domain-containing 2 (FUNDC2) expression was knocked down in 3T3-L1 adipocytes to assess its effects on mitochondrial dynamics, ferroptosis, and adipokine secretion. Next, vascular smooth muscle cells (VSMCs) were cultured in the supernatant of the adipocytes to detect changes in their phenotypic switching and migration.</p><p><strong>Results: </strong>The proteomic results revealed that the expression of the outer mitochondrial membrane protein FUNDC2 was significantly upregulated in the PVAT of SHRs. Additionally, the expression of key proteins that regulate mitochondrial dynamics and ferroptosis was altered significantly in the PVAT of SHRs compared with the PVAT of WKY rats. Upon FUNDC2 knockdown in 3T3-L1 adipocytes, proteins related to mitochondrial dynamics, ferroptosis, and adipokines reversed the changes in their expression. Moreover, in VSMCs cultured with the supernatant of FUNDC2-knockdown adipocytes, the VSMC phenotype and migration changed.</p><p><strong>Conclusion: </strong>Our findings indicated that increased FUNDC2 expression might lead to PVAT dysfunction and abnormal adipokine secretion, potentially through its link to mitochondrial dynamics and ferroptosis in PVAT adipocytes, therefore leading to hypertensive vascular remodeling.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2610587"},"PeriodicalIF":3.5,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ANXA2, DBN1, ZNF385D, and IL6ST: Endothelial cell biomarkers linking atherosclerosis progression to immune microenvironment dysregulation.","authors":"Fenlong Xue, Ying Shi, Yuhui Zhang, Rangfei Zhu","doi":"10.1080/10641963.2026.2627352","DOIUrl":"10.1080/10641963.2026.2627352","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>A total of 66 endothelial cell-associated DEGs were identified, from which four core feature genes (<i>ANXA2</i>, <i>DBN1</i>, <i>ZNF385D</i>, and <i>IL6ST</i>) 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 <i>ANXA2</i> with thalidomide and <i>IL6ST</i> with resveratrol, with binding energies of -6.7 kcal/mol and -7.4 kcal/mol, respectively.</p><p><strong>Conclusion: </strong>Our findings provided new insights for the targeted AS therapy.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2627352"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frailty as a mediator of the association between hyperuricemia and stroke risk: A prospective cohort study.","authors":"Qingchun Song, Xiaokang Tu, Zilong Zheng, Ruilin Liu, Chengming Fan","doi":"10.1080/10641963.2026.2675538","DOIUrl":"10.1080/10641963.2026.2675538","url":null,"abstract":"<p><strong>Background: </strong>Existing evidence on the interrelationship among hyperuricemia, physical frailty, and stroke remains limited and unclear. This study aimed to examine the associations of hyperuricemia and frailty with the incidence of stroke, and to evaluate the potential mediating role of frailty.</p><p><strong>Methods: </strong>We include Chinese adults aged 45 years and above from the China Health and Retirement Longitudinal Study (CHARLS). Serum urate concentrations were measured using an enzymatic colorimetric method, and hyperuricemia was defined as serum urate ≥420 μmol/L. The frailty index (FI) was constructed based on 28 baseline items. Stroke was ascertained based on self-reported, physician-diagnosed events. Multivariable logistic regression and mediation analyses were conducted to examine the associations among hyperuricemia, physical frailty, and stroke.</p><p><strong>Results: </strong>A total of 7462 eligible participants were included in the analysis. Hyperuricemia was positively associated with frailty status (OR = 1.54, 95% CI: 1.02-5.84) and with the incidence of stroke (OR = 4.07, 95% CI: 1.25-13.19). Pri-frail and frail participants exhibited a substantially higher risk of incident stroke (OR = 1.55, 95% CI: 1.11-2.92 and OR = 2.87, 95% CI: 1.29-6.37, respectively). Mediation analysis further indicated that the FI partially mediated the relationship between hyperuricemia and incident stroke, accounting for 10.82% (95% CI: 6.51%-21.65%) of the total effect.</p><p><strong>Conclusions: </strong>Hyperuricemia is associated with an increased risk of stroke, and frailty may partially mediate this association. Early identification and management of frailty in individuals with hyperuricemia may represent a novel, integrative strategy to reduce stroke risk and promote healthy aging.</p>","PeriodicalId":10333,"journal":{"name":"Clinical and Experimental Hypertension","volume":"48 1","pages":"2675538"},"PeriodicalIF":6.8,"publicationDate":"2026-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147970824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}