Cardiovascular Toxicology最新文献

Ferroptosis is considered to be a pathological mechanism of myocardial ischemia-reperfusion injury (MI/RI). Previous studies have shown that death-associated protein kinase 1 (DAPK1) was involved in MI/RI development, but the underlying mechanism remains unclear. Mice with ligation of the left anterior descending artery followed by reperfusion, and HL-1 cells subjected to hypoxia/reoxygenation (H/R) induction were used as MI/RI animal and cell models, respectively. The pathological status of the mouse heart was evaluated by TTC staining, HE staining and echocardiography. Cell viability was examined using CCK-8. DAPK1, SRY-box transcription factor 4 (SOX4) and ferroptosis-related indicators were determined using RT-qPCR, western blot, commercial kits and DCFH-DA method. The interaction between SOX4 and DAPK1 promoter was validated using dual luciferase assay and ChIP assay. In MI/RI mice and H/R-induced cardiomyocytes, DAPK1 and SOX4 expression was abnormally elevated compared with that in control groups. In addition, silencing of DAPK1 or SOX4 improved cardiomyocyte injury and attenuated ferroptosis in H/R-induced cardiomyocytes. At the molecular levels, SOX4 could promote DAPK1 transcription and elevate DAPK1 expression via interacting with the DAPK1 promoter. Furthermore, SOX4 knockdown alleviated cardiomyocyte injury and mitigated ferroptosis through inhibiting DAPK1 expression, thereby relieving MI/RI in mice. Our results reveled that SOX4 promoted cardiomyocyte injury and exacerbated ferroptosis, thereby intensifying MI/RI through increasing DAPK1 expression.

This study aims to mine and analyze adverse events (AEs) of argatroban based on the FAERS database to better understand its safety and potential risks in the real-world. Data from the first quarter of 2004 to the third quarter of 2024 were collected, and researchers employed various signal mining methods such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study collected 54,336,884 reports of AEs, of which 2,233 were related to argatroban. Signal mining identified 110 Preferred Terms involving 25 system organ classes. There were most reports involving adults (≥ 65 years), with a slightly higher proportion in men than women. We identified known AEs, including prolonged coagulation time, hemorrhage, abnormal hepatic function. New potential AE signals were identified, such as vascular pseudoaneurysm, retroperitoneal hematoma, gangrene, thrombotic thrombocytopenic purpura, acute cardiac failure, atrial septal defect, rhabdomyolysis. The median time to event was 2.00 days, with the majority of AEs occurring within 30 days. Analysis of the FAERS database identified argatroban-associated AEs, including newly identified potential risks with the aim of enhancing clinicians' and pharmacists' awareness of drug-related risk signals and facilitate timely preventive and treatment interventions for patient safety.

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.

Myocardial infarction (MI), induced by ischemia and hypoxia of the coronary arteries, presents as myocardial necrosis. Patients often experience intense, prolonged retrosternal pain that is unrelieved by rest or nitrate therapy and is frequently associated with high blood myocardial enzyme levels. Physical effort may exacerbate this anxiety, increasing the likelihood of life-threatening consequences such as arrhythmias, shock, or cardiac failure. Chrysin, a natural flavonoid primarily found in honey and propolis, exhibits anti-inflammatory, antioxidant, anticancer, and antiviral properties. This study utilized MI models and various analytical techniques, including Western blotting, immunofluorescence, quantitative polymerase chain reaction (qPCR), and autodocking, to elucidate the molecular mechanisms underlying the action of chrysin in molecular interactions. Our results demonstrated that Chrysin alleviates apoptosis in cardiomyocytes by decreasing the Bax/Bcl-2 ratio and suppressing caspase-3 activation, actions facilitated by PPAR-γ activation and consequent overexpression of anti-apoptotic proteins. Furthermore, chrysin mitigates cardiac fibrosis by downregulating TGF-β1, collagen I, and α-SMA expression. These effects markedly diminish infarct size and improve heart function in ischemia-reperfusion damage models, ascribed to chrysin's activation of PPAR-γ and SIRT3, together with the regulation of β-catenin pathways. The preclinical data presented in this research establish a foundation for forthcoming clinical studies to assess the safety and effectiveness of chrysin in patients with myocardial infarction. This may facilitate the development of a novel treatment approach for treating MI.

Doxorubicin-induced cardiotoxicity (DIC) is pathologically characterized by oxidative stress and inflammatory cascades, creating an urgent need to identify therapeutic targets modulating these processes. While tumor necrosis factor alpha-induced protein 8 (TNFAIP8) has emerged as a regulator of inflammation and apoptosis, its functional role in DIC remains unexplored. This study systematically investigates TNFAIP8's cardioprotective mechanisms against DIC. A chronic DIC model was established in male C57BL/6 mice through intraperitoneal doxorubicin (DOX) administration (4 mg/kg weekly for 4 weeks; cumulative dose 16 mg/kg). TNFAIP8 knockdown was achieved via AAV9-delivered shRNA through tail vein injection. Multimodal assessment integrating echocardiography, histopathology analysis, and molecular profiling elucidated TNFAIP8's functional and mechanistic contributions. In DOX-induced cardiomyocytes, TNFAIP8 expression was upregulated. The absence of TNFAIP8 markedly reduced DOX-triggered oxidative stress and inflammatory responses. The potential protective mechanism of TNFAIP8 deficiency against DIC involves toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Importantly, administration of the TLR4 activator lipopolysaccharide (LPS) substantially reversed the cardioprotective effects observed with TNFAIP8 deletion. Our findings establish TNFAIP8 as a critical regulator of DIC pathophysiology through TLR4/NF-κB axis modulation. Pharmacological TNFAIP8 inhibition represents a viable therapeutic strategy for mitigating chemotherapy-induced cardiac dysfunction. Future investigations should prioritize developing cardiac-targeted TNFAIP8 inhibitors and validating their efficacy in large-animal DIC models.

Statins, widely used for preventing cardiovascular diseases due to their cholesterol-lowering effects, are associated with potential adverse reactions in some individuals, underscoring the need to understand the factors contributing to statin-related complications. The ATP-binding cassette subfamily G member 2 (ABCG2) gene, which encodes a multidrug transporter, has garnered attention due to its involvement in statin metabolism. Specifically, the rs2231142 polymorphism within ABCG2 has been implicated in altered drug metabolism and pharmacokinetics, potentially influencing statin-related toxicity. Despite previous investigations, findings regarding this association remain inconclusive. Thus, this systematic review and meta-analysis aimed to clarify the correlation between the rs2231142 polymorphism and statin-induced toxicity. Through a comprehensive literature search, seven eligible studies were identified and subjected to rigorous data extraction and quality assessment. Meta-analysis revealed a significant association between the rs2231142 polymorphism and an increased risk of overall statin-induced toxicity, including muscular and hepatic toxicity, with odds ratios of 2.6 and 2.7, respectively. These findings suggest a potential role for ABCG2 polymorphisms in statin-related adverse events and emphasize the importance of personalized treatment strategies in managing statin therapy.

Electronic cigarettes are popular tobacco products that heat e-liquid into an aerosol for inhalation. Since their introduction to the market, electronic cigarettes have been considered a safer alternative to combustible tobacco products. However, most of today's users are adolescents and young adults naïve to tobacco products, who are drawn to e-cigarettes by appealing designs and targeted marketing, resulting in exposure to largely unknown short- and long-term health risks. While the cardiovascular effects of electronic cigarettes remain incompletely understood, there has been a growing concern surrounding their potential acute and chronic impact on cardiovascular health and disease risks. In this review, we examine the components of e-cigarettes and evaluate the cardiovascular effects of both acute and regular e-cigarette exposure, summarizing findings from existing preclinical and clinical studies to provide a comprehensive overview about the topic.

Endocrine disrupting chemicals (EDCs) are exogenous compounds that interfere with the normal functioning of the endocrine system. This effect is crucial for maintaining hormonal balance and regulating various physiological processes. Phthalates, parabens, and triclosan are EDCs found in many personal care products (make-up, shampoo, perfume, shaving foam, moisturizing cream, hair dyes, deodorant), plastics, pesticides, pharmaceuticals, and household cleaning products, and can be inhaled or absorbed by the body through inhalation or skin contact. Atherosclerosis is a major cause of cardiovascular diseases, including coronary artery disease, stroke, and peripheral artery disease. While traditional risk factors for atherosclerosis, such as high cholesterol, hypertension, and smoking, have been extensively studied, emerging evidence suggests that EDCs may also play a significant role in the development and progression of atherosclerosis. Several potential mechanisms have been proposed to explain how EDCs contribute to atherosclerosis. One mechanism involves the activation of nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and estrogen receptors (ERs), by EDCs. Activation of these receptors can lead to dysregulation of lipid metabolism, inflammation, and oxidative stress, all of which are key processes in atherosclerosis development. EDCs have been shown to disrupt endothelial function through various mechanisms. Some of these mechanisms are the formation of reactive oxygen species (ROS) and free oxygen radicals, and impaired nitric oxide (NO) production by EDCs. This literature review aims to explore the current understanding of the role of EDCs in atherosclerosis.

Atypical antipsychotics have experienced a significant increase in use across various disorders, coinciding with a rise in acute intoxication. This retrospective study predicts prolonged QTc interval and the necessity for mechanical ventilation (MV) in patients with acute atypical antipsychotic poisoning using machine learning techniques. This retrospective study included 355 patients with a mean age of 26.1 ± 9.6 years. The overall prevalence of the investigated outcomes was 5.5% for prolonged QTc interval and 7.1% for MV. Eight classifiers were developed, including Logistic Regression, Support Vector Machine, K-Nearest Neighbors, and five tree-based models: Random Forest, XGBoost, LightGBM, CatBoost, and Gradient Boosting Models. Model validation was conducted through external validation using the testing dataset and an internal five-fold cross-validation after optimizing the hyperparameters. As a predictor of prolonged QTc interval, all tree-based models achieved perfect specificity, recall, precision, accuracy, and area under the curve (AUC) of 100% using the training dataset. Similar performance was reported in models predicting the necessity for MV. Upon validation, the tree-based models for predicting prolonged QTc intervals maintained good AUCs, ranging between 0.930 and 0.958 in the training dataset and between 0.927 and 0.949 in the testing dataset. In terms of accuracy, the tree-based models exhibited good values in both external and five-fold cross-validation, with all values above 0.901. The observed declines in recall and precision during the validation of the proposed models underscore the need for future studies to utilize larger validation cohorts, thereby enabling the generalization of the proposed models in relevant clinical settings.

Trastuzumab is a common and effective therapeutic choice for breast cancer treatment. However, the cardiotoxicity induced by this therapy remains a significant challenge, because we lack predictors that help avoid allocating some patients with high risk to this management plan. This study was aimed to evaluate several baseline risk factors such as prolonged QTc interval, age, and lower expression level of estrogen and progesterone receptors that might predict cardiac toxicity after Trastuzumab therapy. This prospective observational study was conducted in Al-Bairouni Hospital at Damascus University. Patients were evaluated with echocardiography and electrocardiography before therapy and three weeks after the last administration of the fourth cycle. A significant Trastuzumab-related cardiotoxicity was determined by a 5% or more reduction in the left ventricular ejection fraction after excluding all other potential causes. A total number of 140 patients with breast cancer, who were indicated Trastuzumab therapy, were recruited for this study. Thirty of them (21.4%) developed Trastuzumab-related cardiotoxicity but all were asymptomatic. Corrected QT interval of more than 450 ms and lower expression level of estrogen and progesterone receptors at baseline were associated with higher susceptibility to develop Trastuzumab-related cardiotoxicity (P = 0.045, P = 0.004, and P = 0.042, respectively). Of note, preexisting cardiac morbidities, age, and chemotherapy accompanying Trastuzumab administration did not reach significant association with cardiotoxicity. Breast cancer patients with prolonged corrected QT interval or lower expression levels of hormone receptors are at a higher risk of developing Trastuzumab-related cardiotoxicity, necessitating careful administration of the therapy.