Cardiovascular Toxicology最新文献

{"title":"Associations of Plasma Metabolite Phenylacetylglutamine on Coronary Plaque Characterization in Patients with ST-Segment Elevation Myocardial Infarction.","authors":"Peng Zhao, Zhongzhi Yu, Wenqiang Song, Suhong Zhao, Cheng Jin, Xinxin Liu, Bo Yu, Jinwei Tian","doi":"10.1007/s12012-025-10067-7","DOIUrl":"https://doi.org/10.1007/s12012-025-10067-7","url":null,"abstract":"<p><p>The gut microbiota-derived metabolite phenylacetylglutamine (PAGln) was associated with adverse events in patients with ST-segment elevation myocardial infarction (STEMI). However, the evidence regarding the association between PAGln and culprit plaque characteristics was limited. Here, we aim to investigate the associations between plasma PAGln and culprit plaque characteristics evaluated by optical coherence tomography (OCT) in patients with STEMI. The associations of PAGln level with culprit plaque characteristics were assessed with logistic regression model in 776 patients imaged by OCT at the time of primary percutaneous coronary intervention. The role of PAGln in plaque stability was investigated by bioinformation analysis. Patients in the high plasma PAGln group had a higher prevalence of culprit thin-cap fibroatheromas (TCFA) (37.4 vs. 30.5%, p = 0.001) and CLIMA-defined high risk plaque (37.1 vs. 30.2%, p = 0.001) compared with those in the low PAGln group. In the multivariate logistic analysis, elevated PAGln level remained independently (traditional risk factors) associated with TCFA (OR 1.95, 95% CI 1.29-2.95, p = 0.001) and CLIMA-defined high risk plaque (OR 1.99, 95% CI 1.31-3.02, p = 0.001). Single-cell RNA sequencing results suggested that PAGln-targeted ACE, MME, MMP9 genes enrich macrophages and may be involved in plaque stability in STEMI patients. This study first revealed that PAGln concentrations were significantly associated with the vulnerable plaque independently, and macrophages may be involved in this process.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291216","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":"Effects of PM2.5 Reduction Interventions on Cardiovascular Indicators: A Meta-analysis.","authors":"Qin Liu, Fenglin Xu, Ping Zhang, Xi Zheng, Fanying Xiang, Shunqing Luo, Shenying Fang, Xizhou An, Yang Bi, Jingyu Chen, Yang Gao, Shihai Zheng, Xiaohua Liang","doi":"10.1007/s12012-025-10064-w","DOIUrl":"https://doi.org/10.1007/s12012-025-10064-w","url":null,"abstract":"<p><p>Exposure to fine particulate matter (PM2.5) is associated with adverse cardiovascular outcomes, but the effectiveness of individual-level interventions to reduce exposure remains unclear. This meta-analysis aimed to assess the effects of four distinct categories of PM2.5 interventions on cardiovascular health including high-efficiency particulate air (HEPA) filters, respiratory protective equipment, improved cookstoves, and other behavioral PM2.5 reduction methods. We systematically searched PubMed, Embase, Web of Science, and the Cochrane library for studies published between December 2002 and March 2025 that reported the cardiovascular effect of PM2.5 reduction. Intervention methods were categorized based on their mechanisms of action and implementation settings. The primary outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP), with secondary outcomes including endothelial function indices, heart rate variability (HRV), and inflammatory markers. A total of 72 trials involving 6,063 participants (age range: 12.4-82 years) were included. Overall, PM2.5 reduction interventions significantly decreased SBP by 1.97 mmHg (95% CI: -2.89, -1.05) and DBP by 1.08 mmHg (95% CI: -1.80, -0.35). Among secondary outcomes, C-reactive protein (CRP) decreased significantly (MD = -0.03mg/dl, 95% CI: -0.06, -0.00, P = 0.042), while no significant changes were observed in interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), or HRV. Subgroup analyses revealed differential effects by intervention type: Air filtration interventions showed the largest effect on SBP (MD = -1.94mmHg, 95% CI: -3.33, -0.55, P = 0.006) compared to other interventions. These findings suggest that PM2.5 reduction interventions could lower blood pressure and reduce markers of systemic inflammation, indicating that personal-level interventions may provide measurable cardiovascular benefits, even with short-term implementation.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243857","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":"Sirtuins as Endogenous Regulators of Cardiac Fibrosis: A Current Perspective.","authors":"Zeinab Farhadi, Mansour Esmailidehaj, Shahab Masoumi, Hossein Azizian","doi":"10.1007/s12012-025-10052-0","DOIUrl":"10.1007/s12012-025-10052-0","url":null,"abstract":"<p><p>Cardiac fibrosis is a pathological condition marked by the excessive accumulation of extracellular matrix (ECM) components, which leads to impaired cardiac function and heart failure. Despite its significant contribution to cardiovascular morbidity and mortality, no effective therapeutic drugs specifically target the inhibition of cardiac fibrosis, largely due to the complex etiological heterogeneity and pathogenesis of this disease. Sirtuins (SIRTs), a family of NAD + -dependent deacetylases, play a critical role in cellular processes such as oxidative stress, inflammation, energy metabolism, mitochondrial function, epithelial-to-mesenchymal transition (EMT), and ECM homeostasis, all of which are implicated in cardiac fibrosis. Growing clinical and experimental evidence suggests that SIRTs regulate the cellular and molecular mechanisms of cardiomyocytes through various biological pathways. Emerging evidence indicates that sirtuin activators, including resveratrol and NAD + precursors, hold therapeutic potential in mitigating cardiac fibrosis. However, the complex and context-dependent roles of sirtuins necessitate further research to fully elucidate their mechanisms and translational applications. As the role of SIRTs in relation to cardiac fibrosis and its associated mechanisms is rarely discussed in the literature, this review comprehensively addresses the roles of the seven mammalian sirtuins (SIRT1-SIRT7) in the pathogenesis and progression of cardiac fibrosis. It highlights the key role of SIRTs as molecular targets for innovative anti-fibrotic therapies, offering new avenues for the treatment of cardiac fibrosis and associated cardiovascular diseases.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1634-1649"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820668","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":"Cardiovascular Risk with Prokinetics: A Self-Controlled Case Series Study Using a Korean Nationwide Health Claims Database.","authors":"Ju-Young Park, Tae-Jin Song, Jinkwon Kim, Sangwook Kang","doi":"10.1007/s12012-025-10044-0","DOIUrl":"10.1007/s12012-025-10044-0","url":null,"abstract":"<p><p>There have been concerns about potential adverse cardiovascular (CV) events associated with prokinetics that enhance gastrointestinal (GI) motility. To evaluate whether prokinetics use was associated with increased CV risk. We conducted a self-controlled case series (SCCS) study using the National Health Claims Database in South Korea. Age-adjusted incidence rate ratios (IRR) for the development of CV events (composite of myocardial infarction and stroke) were estimated by comparing the incidence during the risk period with prokinetics and the control period without prokinetics. This SCCS study included 15,621 participants who experienced CV events and exposure to prokinetics between 2004 and 2019. The risk period with prokinetics had a significantly increased risk for CV events compared to the control period (IRR 1.56, 95% CI 1.48-1.66). When the risk period was categorized according to the time from initiation of prokinetics, CV risk was highest in the first 7 days (IRR 2.29, 95% CI 2.13-2.47), and declined to non-significance in ≥ 15 days (IRR 1.03, 95% CI 0.94-1.13). In the analysis according to the class of prokinetics, CV risk was highest in the order of central dopamine type 2 (D2) receptor antagonist (IRR 2.14, 95% CI 1.95-2.34), peripheral D2 receptor antagonist (IRR 1.37, 95% CI 1.24-1.51), and selective 5-hydroxytryptamine 4 receptor agonist (IRR 1.29, 95% CI 1.17-1.42). The use of prokinetics was associated with an increased risk of CV adverse events, particularly in the early period following initiation of central D2 receptor antagonists.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1591-1603"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667262","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":"Chronic Mercury Exposure Triggers Vascular Remodeling and Impaired Vasoconstriction in Small Intrapulmonary Arteries.","authors":"Ingridy Reinholz Grafites Schereider, Lorraine Christiny Costa Sepulchro Mulher, Nina Bruna de Souza Mawandji, Vanessa Cristina de Oliveira Souza, Fernando Barbosa Junior, Júlia Martins Vieira, Maylla Ronacher Simões, Dalton Valentim Vassallo","doi":"10.1007/s12012-025-10047-x","DOIUrl":"10.1007/s12012-025-10047-x","url":null,"abstract":"<p><p>Mercury exposure is a significant environmental concern due to its toxic effects on the human body, especially on the cardiovascular system. Its accumulation induces oxidative stress, inflammation and endothelial dysfunction in systemic arteries, contributing to the development of cardiovascular diseases. The close relationship between systemic and pulmonary circulation leads us to believe that it must also suffer by the toxic effects of HgCl₂. However, the consequences of HgCl₂ on pulmonary arteries remain unclear. This study aimed to investigate the effects of mercury chloride (HgCl₂) exposure for 60 d on the small intrapulmonary arteries and hemodynamic parameters of male rats. The rats were exposed to HgCl₂ (1st dose, 4.6 μg/kg; subsequent daily doses, 0.07 μg/kg; intramuscular injection). The results revealed that intrapulmonary arteries from exposed rats exhibited reduced contractile responses to potassium chloride and the thromboxane A2 receptor agonist U46619, along with thinning of the arterial wall, which is indicative of vascular remodeling. Impaired pulmonary vasoconstriction in the HgCl₂ group was associated with increased nitric oxide (NO) production and elevated hydrogen peroxide (H₂O₂) levels. In addition, increased production of superoxide anion (O₂^•-) and reduced superoxide dismutase (SOD) expression were observed and indicates an environment of oxidative stress. Furthermore, HgCl₂ increased systemic blood pressure in conscious animals but reduced left ventricular systolic pressure in anesthetized animals. These findings suggest that chronic HgCl₂ exposure induces pulmonary vascular dysfunctions, primarily through enhanced NO and ROS signaling as an adaptive mechanism.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1491-1505"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834062","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":"Caffeine Intake Attenuates the Association of Cadmium Exposure with Cardiovascular Disease: National Health and Nutrition Examination Survey (NHANES) 2003-2016.","authors":"Shuaijie Chen, Hailin Zhang, Qiong Su, Xiaoyan Lin, Kai Kang, Zhongxing Zhou, Lishan Zeng, Yifei Lin, Hongzhuang Wang, Feng Peng, Jinxiu Lin, Dajun Chai","doi":"10.1007/s12012-025-10031-5","DOIUrl":"10.1007/s12012-025-10031-5","url":null,"abstract":"<p><strong>Background: </strong>Cadmium exposure has been linked to an increased risk of cardiovascular disease (CVD). Moderate caffeine intake may reduce the risk of CVD. Whether caffeine intake attenuates the association of cadmium exposure with CVD remains unknown.</p><p><strong>Methods: </strong>The study used cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016. Cadmium exposure was estimated by urinary cadmium after adjusting for urinary creatinine (UCd/Cr, μg/g). Caffeine intake was determined using the average of two 24-h dietary recalls. Logistic regression models were used to examine the association of cadmium exposure with CVD and to evaluate the multiplicative interaction between caffeine intake and cadmium exposure.</p><p><strong>Results: </strong>A total of 7,094 adults aged 20 or older were included in the study, of whom 827 had CVD. The multivariate-adjusted odds ratio (OR) of participants in the highest quartile was 2.10 (95% confidence interval: 1.34-3.28) for CVD compared to participants in the lowest UCd/Cr quartile. The OR of ln-UCd/Cr as a continuous variable was 1.46 (95% confidence interval: 1.23-1.73). Moreover, a significant interaction between caffeine intake and cadmium exposure on CVD was observed (P for interaction = 0.004). The relatively lowest ORs of cadmium exposure with CVD were observed in participants with low or moderate caffeine intake (caffeine intake quartile 2 and quartile 3) in almost all subgroups.</p><p><strong>Conclusions: </strong>Higher cadmium exposure was associated with increased CVD risk in US adults. Low-to-moderate caffeine intake tends to attenuate this association. Further studies are needed to confirm causality and underlying mechanisms.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1506-1522"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616334","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":"Per- and Polyfluoroalkyl Substances (PFAS) Enhance Cholesterol Accumulation and Dysregulate Inflammatory Responses in Macrophages.","authors":"Jack C Connolly, Yasuhiro Ishihara, Emma Sawaya, Valerie Whitfield, Nicole Garrity, Rajveer Sohata, Mark Tsymbal, Alyssa Lundberg, Michele A La Merrill, Jamie C DeWitt, Allison K Ehrlich, Christoph F A Vogel","doi":"10.1007/s12012-025-10048-w","DOIUrl":"10.1007/s12012-025-10048-w","url":null,"abstract":"<p><p>Epidemiological studies and in vivo animal models have shown that exposure to PFAS can lead to cardiovascular toxicity and promote atherosclerosis. In this study, we explored the effects of PFOA and PFOS exposure on lipid accumulation in macrophages and analyzed critical markers of foam cell formation, which are early precursors of atherosclerotic lesions. Our results demonstrate that PFOS and PFOA enhance lipid and cholesterol accumulation in human U937-derived macrophages, which is characteristic of foam cells. PFOS and PFOA induced the activity of the peroxisome proliferator-activated receptor gamma (PPARγ) and treatment with a PPARγ antagonist partly reversed the accumulation of lipids after PFAS exposure. Furthermore, the results show that PFOS and PFOA activate (NF)-erythroid-derived 2 (E2)-related factor 2 (Nrf2) and induce markers of oxidative stress. Gene expression analysis revealed that mRNA levels of interleukin-1β (IL-1β) and plasminogen activator inhibitor-2 (PAI-2) were upregulated in a time- and concentration-dependent manner in PFOS- and PFOA-treated macrophages. The expression of other key atherosclerosis-related enzymes, including cytochrome P450 8B1 (CYP8B1) and lanosterol synthase (LSS), was downregulated, whereas the expression of cyclooxygenase 2 (COX-2) and aldo-keto reductase family 1 member C3 (AKR1C3) was induced by PFOS and PFOA. Additionally, elevated levels of matrix metalloproteinases (MMP)-1 and MMP-12 were found in PFOS- and PFOA-treated cells, which were associated with increased cell migration. Furthermore, PFOS and PFOA enhanced the expression of IL-1β when macrophages were activated; however, elevated levels of IL-6 and COX-2 in activated macrophages were repressed by PFOS and PFOA. Together, the findings indicate that PFAS exposure modifies immune responses and promotes lipid accumulation in macrophages, potentially contributing to foam cell and plaque formation in atherosclerosis.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1455-1470"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728119","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":"Construction of a Machine Learning-Based Clopidogrel Resistance Risk Prediction Model.","authors":"Ruo-Ying Wang, Shui-Di Yan, Jian-Qi Zeng, Tong Mu, Ya Yan, Yuan-Yi Zhao, Lin Xie, Li-Li Liu","doi":"10.1007/s12012-025-10026-2","DOIUrl":"10.1007/s12012-025-10026-2","url":null,"abstract":"<p><p>Clopidogrel is extensively utilized for the prevention and treatment of cardiovascular, cerebrovascular, and other arterial circulation disorders attributed to platelet hyperaggregation. Nevertheless, its antiplatelet efficacy displays substantial individual variability and unpredictability. Our aim was to develop a machine learning model based on clinical data, incorporating various laboratory indicators, to predict the risk of clopidogrel resistance in clinical patients. This study included 1592 cardiovascular disease patients treated with clopidogrel. Potential predictive variables included age, sex, hematological, coagulation, biochemical parameters, and CYP2C19 genetic polymorphisms. Lasso regression and multivariable logistic regression were used for variable selection. Modeling was performed using Logistic Regression, LGBM Classifier, Random Forest Classifier, and SVC machine learning models, followed by model comparison, to ultimately construct the clopidogrel resistance risk prediction model. The clopidogrel resistance rate increased year by year from 2020 to 2022, but decreased slightly in 2023. There was a significant difference in clopidogrel resistance rate among different years (χ² = 49.969, P = 0.000). Predictive variables included white blood cell count, hemoglobin level, platelet count, fibrinogen, triglycerides, D-Dimer, mean platelet volume, prothrombin time ratio, uric acid, glycated hemoglobin, and apolipoprotein B. The Random Forest Classifier machine learning method yielded a CR risk prediction model with AUC = 0.8730 and accuracy = 0.8033, demonstrating good predictive capability for identifying the risk of clopidogrel resistance after clinical use of clopidogrel. This study developed a highly predictive clopidogrel resistance risk prediction model, which can assist in clinical decision-making for better treatment strategies.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1548-1560"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625331","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":"Effects of Cardiac Rehabilitation Combined with Enhanced External Counterpulsation on Heart Rate Variability and Autonomic Nervous Function in Chronic Heart Failure.","authors":"Yiliang Yan, Zichen Han, Bowen Zhou, Kui Li, Jintao Hu, Sigong Yang, Jun Zhang, Xuemin Hu","doi":"10.1007/s12012-025-10027-1","DOIUrl":"10.1007/s12012-025-10027-1","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Heart rate variability and autonomic dysfunction are critical determinants of prognosis in patients with chronic heart failure (CHF). Despite advancements in pharmacological interventions, the rates of hospital readmission and the decline in quality of life remain substantial. Therefore, investigating the impact of cardiac rehabilitation in conjunction with enhanced external counterpulsation (EECP) on heart rate variability and autonomic function in patients with chronic heart failure is of considerable clinical significance. A total of 120 patients with CHF who were hospitalized in the Department of Cardiology in our hospital from May 2022 to October 2023 were retrospectively analyzed. Based on different intervention methods, they were divided into a control group (n = 56) and an observation group (n = 64). The control group received conventional anti-heart failure drug treatment, and the observation group was given cardiac rehabilitation combined with EECP therapy. The two groups were compared in terms of cardiac function indicators [left ventricular end-diastolic diameter (LVEDD), left ventricular end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF)], heart rate variability indicators [standard deviation of sinus RR intervals (SDNN), root mean square of successive differences in adjacent NN intervals (rMSSD), percentage of adjacent NN interval differences exceeding 50 ms (pNN50), standard deviation of the average value of sinus RR interval every 5 min (SDANN), low-frequency power (LF), high-frequency power (HF), and low- and high-frequency power ratio (LF/HF)], autonomic nervous function indicators [heart rate recovery at 1 min of recovery period (HRR1), cardiac chronotropy response], Borg rating of perceived exertion scale (Borg scale), Chinese questionnaire of quality of life in cardiovascular diseases patients, and one-year follow-up outcomes, including the incidence of adverse events and rehospitalization rate. Univariate and multivariate logistic regression analyses were conducted to assess factors affecting rehospitalization within one year in CHF patients. After the intervention, both groups showed significant reductions in LVEDD and LVEDV compared to pre-intervention levels, with a more pronounced decrease in the observation group, indicating a statistically significant difference compared to the control group (P &lt; 0.05). Additionally, LVEF levels in both groups increased significantly post-intervention, with the observation group showing significantly higher LVEF than the control group (P &lt; 0.05). SDNN, SDANN, rMSSD, and pNN50 significantly increased in both groups post-intervention, with higher levels in the observation group than in the control group (P &lt; 0.05). Both groups showed significant increases in LF and HF compared to pre-intervention levels, with higher LF and HF and a lower LF/HF ratio in the observation group compared to the control group (P &lt; 0.05). HRR1 and cardiac chronotropic response sig","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1561-1574"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788342","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":"Yoda1/Piezo1 Alleviates Lipopolysaccharide-Induced Cardiac Injury via AMPK-Mediated Mitophagy.","authors":"Yiheng Yang, Qingshan Tian, Feng Qiu, Jiangfeng Tang, Zhenzhong Zheng, Peng Yang","doi":"10.1007/s12012-025-10045-z","DOIUrl":"10.1007/s12012-025-10045-z","url":null,"abstract":"<p><p>The role of the mechanosensitive ion channel Piezo1 in septic cardiomyopathy remains unclear. This study investigated the role of Piezo1 in septic cardiomyopathy, focusing on the effects of its activation by Yoda1, an effective selective Piezo1 agonist, in LPS-induced cardiac injury models. In vivo, Yoda1 treatment improved cardiac function, enhanced mitophagy, and activated AMPK signaling in LPS-treated mice. In vitro, Yoda1 protected primary cultured cardiomyocytes from LPS-induced oxidative stress, improved mitochondrial function, and increased PINK1/Parkin-mediated mitophagy, whereas the Piezo1 inhibitor GsMTx4 had minimal effects. Western blot analysis confirmed the activation of the PINK1/Parkin and AMPK pathways by Yoda1 in cardiomyocytes. Notably, inhibiting AMPK signaling reduced the protective effects of Yoda1, underscoring the crucial role of AMPK in mitophagy regulation. These findings indicate that Yoda1 may serve as a potential therapeutic agent for LPS-induced cardiac injury, acting primarily through the regulation of mitophagy via the Piezo1/AMPK/PINK1/Parkin signaling pathway.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1604-1615"},"PeriodicalIF":3.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697724","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}