Cardiovascular Toxicology最新文献

{"title":"Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.","authors":"Varsha G Desai","doi":"10.1007/s12012-026-10107-w","DOIUrl":"10.1007/s12012-026-10107-w","url":null,"abstract":"<p><p>Anthracycline-induced cardiotoxicity remains a major clinical challenge, often progressing to heart failure years after therapy. Conventional cardioprotective agents, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers, are widely used to preserve cardiac function; however, their effectiveness is limited by their inability to comprehensively address the complex, multifactorial pathophysiology of anthracycline-induced cardiotoxicity. This underscores the critical need for more effective and mechanism-based cardioprotective strategies that directly target the underlying molecular mechanisms, particularly oxidative stress and mitochondrial dysfunction. In recent years, the apelin-APJ signalling axis has attracted increasing attention as a potential therapeutic target in cardiovascular diseases owing to its multifaceted biological actions, including positive inotropy, vasodilation, anti-inflammatory, anti-fibrotic, anti-apoptotic, antioxidant, and pro-angiogenic effects. These pleiotropic actions are primarily mediated through the activation of key signalling pathways such as phosphoinositide 3-kinase/protein kinase B, extracellular signal-regulated kinases 1/2, and AMP-activated protein kinase. Given that these signalling cascades are disrupted during anthracycline-induced cardiotoxicity, pharmacological activation of the apelin-APJ axis may represent a promising avenue to mitigate anthracycline-associated cardiac injury with greater efficacy than conventional therapies. While native apelin isoforms (apelin-12, -13, -17, and [Pyr¹]apelin-13) are limited by their short half-lives, chemically modified analogues such as LIT01-196 and apelin-17(A2) exhibit enhanced stability and efficacy, with demonstrated cardioprotective effects in preclinical cardiovascular models and patients with chronic heart failure. However, their therapeutic potential in anthracycline-induced cardiotoxicity remains largely unexplored. This review highlights its promise as a novel cardioprotective strategy for mitigating anthracycline-induced cardiotoxicity.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Associations Between Cadmium Exposure and Mortality Risk in Cardiovascular Disease Patients: A Cohort Study Integrating Molecular Mechanisms of Myocardial Dysfunction.","authors":"Caili He, Kaiwen Wang, Ruiqi Yang, Xinyi Li, Zicong Shao, Li Ma, Yongbin Lu, Xiaowei Niu, Siyu Zhang, Yongxiang Wang","doi":"10.1007/s12012-026-10117-8","DOIUrl":"10.1007/s12012-026-10117-8","url":null,"abstract":"<p><p>Heavy metal cadmium (Cd) exposure is associated with increased cardiovascular disease (CVD) risk, yet sex-specific differences in Cd exposure’s impact on CVD patient mortality and underlying mechanisms remain unclear. Using the national health and nutrition examination survey (NHANES) database and its follow-up mortality data (1,413 CVD patients: 652 deaths [46.14%], 761 survivors [53.86%]), we investigated the specific roles of Cd exposure in CVD. Cox regression showed that elevated blood Cd were more strongly associated with increased all-cause mortality risk in males (HR = 1.67, 95% CI: 1.00-2.78), whereas higher urinary Cd conferred a greater risk in females (HR = 2.17, 95% CI: 1.20–3.92). Restricted cubic spline analysis showed that, in males, blood Cd exhibited a linear dose-response with all-cause mortality (P for nonlinear = 0.128), while urinary Cd demonstrated a significant nonlinear relationship (P for nonlinear = 0.016). Interaction models further revealed that the interactions between blood Cd and diabetes mellitus (DM) (P for interaction = 0.013), as well as between urinary Cd and DM (P for interaction = 0.017), significantly amplified all-cause mortality risk in males. Network toxicology and bioinformatics analyses identified formyl peptide receptor 1 (FPR1) as a key mediator of CdCl₂-associated CVD progression, with elevated expression in CVD patients (log2FC = 0.71, P < 0.001). Molecular docking (free energy = -2.620 kcal/mol), Western blot, and qPCR confirmed that FPR1 can bind CdCl₂ and is dose-dependently upregulated in AC16 cardiomyocytes. Overall, we found that male CVD patients exhibit a marked, dose-dependent increase in all-cause mortality risk associated with Cd exposure, which is further exacerbated by its synergy with DM. Mechanistically, Cd appears to promote CVD progression by disrupting FPR1 signaling in cardiomyocytes. These findings suggest that prevention strategies should integrate metabolic disease management with environmental Cd control, and highlight FPR1 as a promising therapeutic target.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 5","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zebrafish Model Reveals Early Electrocardiographic and Molecular Signatures of Doxorubicin-Induced Cardiotoxicity.","authors":"Zih-Yin Lai, Chi-Ying Lee, Yu-Ching Chiu, Chia-Hung Lin, Chung-Chi Yang, Chia-Chia Ho, Lawrence Yu-Min Liu, Yung-Jen Chuang","doi":"10.1007/s12012-026-10113-y","DOIUrl":"10.1007/s12012-026-10113-y","url":null,"abstract":"<p><p>Doxorubicin (DOX) is a highly effective anthracycline widely used in cancer therapy but limited by its dose-dependent cardiotoxicity, which may result in arrhythmia, dilated cardiomyopathy, and heart failure. Conventional surveillance tools, including echocardiography and serum biomarkers, often identify injury only after substantial cardiac dysfunction has occurred. This underscores the need for early markers with mechanistic relevance. In this study, we developed an integrated zebrafish platform combining pathophysiological evaluation, electrocardiography (ECG), and transcriptomic profiling to establish a novel approach for early detection of DOX-induced cardiotoxicity (DIC). Consistent with human and mammalian models, DOX administration in adult zebrafish resulted in ventricular enlargement, myocardial fiber disarray, and elevated troponin I levels. ECG recordings revealed dose-dependent conduction disturbances, notably progressive PR interval and QRS prolongation, with P wave widening at higher doses. These findings identify the PR interval as a sensitive, early index of conduction impairment in the zebrafish DIC model, consistent with clinical reports linking PR prolongation to adverse outcomes. RNA sequencing further identified transcriptional pathways associated with conduction delay, with dysregulation of sodium channels (scn5lab, scn1lab), gap junction proteins (cx43, cx40.8), and transcriptional regulators (nkx2.5, tbx family). Notably, scn1lab expression declined progressively, cx43 and nkx2.5 were upregulated, showing temporal changes that co-occurred with the observed ECG and structural phenotypes. Together, these results support adult zebrafish as a scalable platform for cardiotoxicity screening and highlight PR interval prolongation as an early electrophysiological marker of DOX-associated conduction disturbance. The transcriptomic signatures are presented as correlative, hypothesis-generating candidates relevant to cardiac conduction and remodeling.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular Health and Fluoride Toxicity: A Qualitative Systematic Review.","authors":"Rashi Baltoo, Ruhi Thakur, Srishti Rana","doi":"10.1007/s12012-026-10114-x","DOIUrl":"10.1007/s12012-026-10114-x","url":null,"abstract":"<p><p>PURPOSE: This review aims to comprehensively integrate and qualitatively synthesize the current evidence on fluoride-induced cardiotoxicity. Specifically, it evaluates in vitro, animal, and human studies to examine mechanistic pathways including oxidative stress, mitochondrial dysfunction, inflammation, and apoptosis and associated structural and functional cardiac alterations. By integrating findings from experimental and observational research, this review assesses the extent to which existing data support fluoride-related cardiac effects and highlights areas requiring deeper mechanistic and clinical investigation. METHODS: A systematic literature search was conducted using PubMed, Google Scholar to identify studies between 1957 and 2024 on fluoride-induced cardiovascular outcomes. Predefined inclusion and exclusion criteria were applied to select the relevant in vitro, animal, and human studies. Data were extracted and qualitatively synthesized. Keywords included “fluoride,” “cardiotoxicity,” “oxidative stress,” “apoptosis,” and “histological alterations,” with a focus on both in vivo and in vitro models. RESULTS: Reviewed studies reveal that fluoride exposure report myocardial necrosis, edema, vacuolization, and fiber disorganization. Biochemical data show elevated oxidative stress (MDA), reduced antioxidants (SOD, CAT, GSH), dyslipidaemia, and increased inflammatory and cardiac injury markers (TNF-α, IL-1β, CK-MB, cTnI). The in vitro findings further demonstrate mitochondrial-mediated apoptosis including cytochrome c and caspase-9 activation, supporting fluoride’s cardiotoxic mechanisms at both tissue and cellular levels. CONCLUSION: Fluoride exposure is associated with histological alterations, oxidative stress, dyslipidaemia, inflammation, and mitochondrial-mediated apoptosis in experimental models. These outcomes support the biological plausibility of fluoride-induced cardiac dysfunction. However, available human evidence remains limited, precluding definitive conclusions. Further longitudinal and mechanistic studies are needed to clarify the cardiovascular implications of chronic fluoride exposure and potential mitigation strategies.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microplastics and Nanoplastics in Cardiovascular Disease: An Emerging Cardiovascular Risk Factor.","authors":"Alberto Polimeni, Domenico Simone Castiello, Rossella Quarta, Tommaso Gori, Giovanni Martino, Letizia Rosa Romano, Federica Meringolo, Giovanni Lopes, Masakazu Yasuda, Ciro Indolfi, Antonio Curcio","doi":"10.1007/s12012-026-10112-z","DOIUrl":"10.1007/s12012-026-10112-z","url":null,"abstract":"<p><p>Microplastics and nanoplastics (MNPs) have become pervasive contaminants in air, water, and food, leading to continuous human exposure. Contrary to the long-standing assumption that these particles are biologically inert, accumulating evidence now shows that MNPs cross epithelial and endothelial barriers, circulate systemically, and accumulate in cardiovascular tissues. Experimental, translational, and early clinical studies demonstrate that some MNPs can induce oxidative stress, endothelial dysfunction, mitochondrial injury, immune activation, and coagulation pathway dysregulation, mechanisms that converge on atherosclerotic development and progression, plaque destabilization, atherothrombosis, and cardiac remodeling. Recent human data identifying MNPs in carotid and coronary plaques, arterial specimens, thrombi, and cardiac tissues provide direct proof-of-concept for their cardiovascular involvement. These findings position MNPs as an emerging cardiovascular risk factor, with implications for prevention, patient risk stratification, and environmental health policy. Major knowledge gaps remain, including the absence of standardized biomarkers of exposure, dose–response quantification, and longitudinal clinical cohorts. Recognizing environmental plastics as cardiovascular toxins demands urgent, multidisciplinary investigation and integration of environmental exposure into cardiovascular disease prevention frameworks.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-Scale Signal Detection and Personalized Risk Prediction for Cardiovascular Drug Adverse Reactions in Elderly Patients: Real-World Evidence from Western China.","authors":"Zimeng Li, Shuzhi Lin, Yifang Shen, Lin Yin, Qian Liu, Tian Sun, Xingfang Xia, Bianling Feng","doi":"10.1007/s12012-026-10110-1","DOIUrl":"10.1007/s12012-026-10110-1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;BACKGROUND: In the context of global ageing, the incidence of adverse drug reactions (ADRs) with use of cardiovascular drugs in elderly patients is increasing, with important implications for the health and well-being of elderly people as well as the societal burden on healthcare systems. There is an urgent need for systematic analysis of cardiovascular ADR data and the identification of risk signals to enhance personalized risk prediction and guidance for the rational use of cardiovascular drugs in elderly patients. METHODS: We collected data from the ADR reporting system of the Shaanxi Provincial Centre for Adverse Drug Reaction Monitoring in China. We conducted statistical analysis using 21,501 ADR data records related to the use of cardiovascular drugs by elderly patients from 2018 to 2023. We applied disproportionality analysis to identify drug risk signals without performing a case-by-case analysis. We used restricted cubic spline analysis to quantify the relationship between patient age and the risk of ADRoccurrence. Additionally, association rule mining was applied to analyse multidimensional association patterns among patient characteristics, drugs, and ADRs. We explored the fundamental causes of ADR occurrence and proposed corresponding medication recommendations and preventive measures. RESULTS: Signal mining results showed that 102 effective risk signals were identified at System Organ Class level. The strongest signal was associated with endocrine disorders caused by Class III antiarrhythmics (reporting odds ratio = 1023.41, information component = 5.11); nitrates and nitrites for angina pectoris causing nervous system disorders occurred most frequently (2819 cases). We identified 321 effective risk signals at High-Level Term level. Angiotensin-converting enzyme (ACE) inhibitors causing cough occurred most frequently (1104 cases); statins caused various ADRs such as hepatic dysfunction and muscular injury. Restricted cubic spline analysis showed that the risk of patients experiencing headaches when using nitrates and nitrites was highest at age 70.28 years (p &lt; 0.001). The risk of coughassociated with use of ACE inhibitors was high after age 71.58 years (p &lt; 0.05). Through multidimensional association rule mining, four significant strong association rules were identified; that regarding female patients experiencing coughing when using ACE inhibitors had the highest confidence (0.676) and lift (11.226), indicating a greater risk of ADRs. CONCLUSION: We comprehensively analysed cardiovascular ADR data in elderly patients, revealing potential drug safety issues and establishing individualized ADR warnings based on patient characteristics. It should be noted that the disproportionality analysis is a hypothesis generating approach and insufficient for causal inference. Our findings will help optimize clinical treatment plans for cardiovascular drugs and promote the rational use of cardiovascular drugs in elderly patients to achieve ","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Real-World Disproportionality Analysis of Drug-Induced Heart Failure: Integrating FAERS Database and AHA Statement.","authors":"Da Li, Yidan Dong, Lei Yao, Xiaozhe Chen, Yunfeng Li, Xiaohong Deng, Jianhua Li, Mingzhu Wang, Deyu Fu","doi":"10.1007/s12012-026-10115-w","DOIUrl":"10.1007/s12012-026-10115-w","url":null,"abstract":"<p><p>Heart failure (HF), the advanced stage of diverse cardiac conditions, poses a significant public health challenge. This study analyzes adverse event (AE) signals associated with HF within the FDA Adverse Event Reporting System (FAERS) database, offering critical insights to guide rational medication use in clinical settings. Adverse event reports (AERs) associated with HF in the FAERS database, spanning from the first quarter of 2004 to the fourth quarter of 2024, were analyzed. The potential HF risk of drugs was assessed using the disproportionality analysis, with findings juxtaposed against the American Heart Association (AHA) drug list. Drug-induced HF cases showed equivalent distribution between male and female, and high rates of rehospitalization and mortality. Prominent hypoglycemic drugs associated with HF included rosiglitazone, pioglitazone, and saxagliptin. Combination therapies, such as metformin/saxagliptin and metformin/rosiglitazone, also demonstrated elevated risks. In the context of pulmonary hypertension, drugs like macitentan, selexipag, and epoprostenol were particularly notable. Analysis against the AHA drug list confirmed stronger signal strength and frequency among Class A drugs, validating our results. Furthermore, drugs not flagged as positively signaling in the AHA registry, such as amiodarone, aliskiren, and testosterone, merit closer scrutiny due to their potential for adverse reactions. Our analysis of the FAERS database has identified medications associated with potential HF risks, providing valuable evidence to inform clinical decision-making and promote the safe use of medications.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Evaluation of Vanillin Flavor in E-Liquid Aerosols on Endothelial Cell Function: Findings from the Replica Project.","authors":"R Emma, A Sun, K Partsinevelos, S Rust, V Volarevic, R Lesmana, A Giordano, H Goenawan, M I Barliana, A Arsenijevic, N Kastratovic, V Markovic, B Spasic, A Distefano, L Orlando, G Carota, R Polosa, Massimo Caruso, G Li Volti","doi":"10.1007/s12012-026-10111-0","DOIUrl":"10.1007/s12012-026-10111-0","url":null,"abstract":"<p><p>There are challenges that require collaboration among researchers to ensure that tobacco harm reduction strategies are evidence-based. A key challenge is evaluating the safety of flavors in e-cigarettes. Many flavorings are deemed “generally recognized as safe” (GRAS) for ingestion, but this does not guarantee their safety when inhaled. The Replica international research group is dedicated to the replication of studies on tobacco alternatives. As part of this effort, the group conducted a conceptual replication of the vanillin-specific experiments from the study by Fetterman et al. (2018), with the goal of validating their conclusions regarding this compound. We used Aspire Zelos 3 e-cigarette and prepared e-liquids containing propylene glycol, vegetable glycerin, and vanillin. The e-liquids were vaporized under regular (1 Ohm coil, 14 watts) and sub-Ohm (0.3 Ohm coil, 200 °C) settings using a vaping machine, following ISO20768:2018 puffing regime. The vapor was collected into a trapping solution to prepare aqueous extracts for treating human aortic endothelial cells. We evaluated cytotoxicity, oxidative stress, nitric oxide bioavailability, and inflammation addressing some gaps reported in the original study. We observed some harmful effects mostly attributable to ethanol used to trap vanillin, but no harmful effects from vanillin. Our results confirm the endothelial cell dysfunction observed in the original paper, but clarify that these effects are mainly attributable to ethanol and not to vaporized vanillin, indicating that, under the experimental conditions applied, vanillin does not elicit significant adverse effects on vascular endothelial cells. However, further research is needed to confirm its toxicological profile.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydroxysafflor Yellow A Attenuates Sepsis-Induced Cardiac Dysfunction by Inhibiting Ferroptosis via Activation of Thioredoxin.","authors":"Yanke Chen, Xu Cai, Wenbin Nan, Zhenyu Peng","doi":"10.1007/s12012-026-10116-9","DOIUrl":"10.1007/s12012-026-10116-9","url":null,"abstract":"<p><p>Ferroptosis is increasingly recognized as a key driver of sepsis-induced cardiac dysfunction. Hydroxysafflor yellow A (HSYA), a bioactive flavonoid, shows cardioprotective properties, but its role in ferroptosis remains unclear. Network pharmacology and molecular docking predicted targets of HSYA related to ferroptosis and sepsis-induced cardiac dysfunction. Functional effects were validated in LPS-stimulated H9C2 cells and in cecal ligation and puncture (CLP) septic mice. Cardiac function, biochemical markers, oxidative stress indices, and protein expression of GPX4, xCT, ACSL4, COX-2 and TXN were evaluated. HSYA improved cardiac function and reduced injury in septic mice. It suppressed ferroptosis by lowering Fe²⁺, MDA, ROS, ACSL4 and COX-2, restoring GSH, and upregulating GPX4 and xCT. TXN was screened as a central mediator, and its inhibition abrogated HSYA's benefits. HSYA protects against septic cardiac dysfunction by inhibiting ferroptosis via TXN activation, highlighting TXN as a novel therapeutic target.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Environmental Chemicals Phthalates and Stroke Among the US Adults: A Cross-Sectional Study.","authors":"Qiang Yang, Peirun Wu, Hongjie Li, Ruifeng Yang, Yuanhao Luo, Mingze Li, Shibo Yin, Xiangji Dang, Yan Liu","doi":"10.1007/s12012-026-10108-9","DOIUrl":"10.1007/s12012-026-10108-9","url":null,"abstract":"<p><p>Stroke has a multifactorial etiology, and phthalates, as widely used environmental chemicals, may play an underexplored role in cerebrovascular health. This study aimed to evaluate the association between urinary phthalate metabolites and stroke risk using data from the National Health and Nutrition Examination Survey (NHANES), complemented by network toxicology, molecular docking, and machine learning approaches. We analyzed data from 10,771 adult participants in NHANES (2003-2018) who had complete records of stroke status, urinary phthalates, and clinical covariates. Multivariable logistic regression and restricted cubic spline (RCS) models were used to assess associations. We constructed protein-protein interaction networks and performed molecular docking to identify potential toxicological targets. Five machine learning algorithms were employed to develop predictive models for phthalate-related stroke risk. Higher levels of MECPP, MCPP, MNBP, and MEOHP were significantly associated with increased stroke prevalence. Network toxicology identified SRC as a key target, and molecular docking confirmed strong binding affinity between MBZP and SRC. Among the machine learning methods, Random Forest achieved the highest predictive performance (AUC = 0.833). Notably, moderate coffee consumption (≤ 170 g/day) was significantly associated with a reduced risk of stroke (OR = 0.63, 95%CI: 0.51-0.77), suggesting potential dietary mitigation against phthalate-related stroke risk. Our findings demonstrate that certain phthalates may increase stroke risk via molecular pathways involving SRC. Furthermore, moderate coffee consumption may mitigate the adverse cerebrovascular effects of these environmental pollutants.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 4","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}