Cardiovascular Toxicology最新文献

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.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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.

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 < 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 < 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 < 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 < 0.05). HRR1 and cardiac chronotropic response sig

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.

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.

Sepsis causes systemic organ and tissue dysfunction, among which myocardial injury has become an urgent clinical problem. Homeodomain-interacting protein kinase 2 (HIPK2) is a serine-threonine kinase that plays an important role in cellular activities. In this study, we investigated the regulatory role of HIPK2 regarding the level of ferroptosis in septic myocardial injury. Trends in ferroptosis and HIPK2 expression were observed over time in a mouse model of sepsis in which cecum ligation perforation was performed. Lipopolysaccharide (LPS)-treated H9c2 cells were used to establish the experimental model, and both HIPK2 overexpression and HIPK2 knockdown H9c2 cells were used to measure the levels of inflammatory markers and ferroptosis-associated proteins. The experimental data revealed that the model mice exhibited greater degrees of myocardial injury, cardiac dysfunction, and ferroptosis compared with normal sham-operated mice, and these effects progressively worsened with increasing duration of sepsis. HIPK2 expression progressively decreased with a prolonged duration of sepsis. Compared with the control H9c2 cells, the LPS-treated H9c2 cells exhibited decreased cell viability and increased cytotoxicity, ferroptosis, and inflammatory responses. HIPK2 overexpression downregulated the levels of inflammatory and ferroptosis mediators, whereas HIPK2 knockdown demonstrated the opposite effects. HIPK2 may play a protective role against septic myocardial injury by modulating ferroptosis.

This study investigated blood selenium (Se) levels in chronic heart failure (CHF) patients and their correlation with cardiac function, followed by a meta-analysis of Se supplementation efficacy. We enrolled 191 CHF patients, measuring blood Se via 2,3-diaminonaphthalene fluorometry. Data were analyzed using SPSS 25.0 and GraphPad Prism 8.0. A systematic review of randomized trials on Se supplementation for CHF was conducted (RevMan 5.3 and Stata 16.0). CHF patients exhibited significantly lower blood Se (P_2.5-P_97.5: 55.12-81.38 μg/L; median: 67.04 μg/L) versus healthy controls. Lower Se levels correlated with obesity (P = 0.001), rural residence (P = 0.009), hypertension (P = 0.038), and advanced cardiac dysfunction (class III/IV vs. I/II, P = 0.002). Se inversely correlated with CRP (r =  - 0.22, P = 0.026). Meta-analysis revealed that Se supplementation reduced systolic blood pressure (P = 0.04) but increased LVESV (SMD = 0.21, P = 0.04). CHF patients frequently exhibit Se deficiency, linked to BMI, cardiac function, and inflammation. Hypertension and low Se may exacerbate cardiac dysfunction, while controlled Se supplementation could improve outcomes.

Lead poisoning remains a significant threat to both human and animal health, with cardiovascular dysfunction being one of its primary adverse effects. This study aimed to investigate the function of the right atrium and right ventricle in 12-month-old male rats exposed to 5.5, 11, and 22.88 mg/kg body weight of lead acetate, injected intraperitoneally three times a week for six weeks. Lead exposure resulted in a reduction in blood pressure (11 mg/kg b.w.) and QRS amplitude, and a lowering of the isoelectric line. Lead exposure led to a dose-dependent shift in the myosin heavy chain (MHC) ratio toward the slower β-MHC isoform in the right ventricle, whereas no changes were detected in the right atrium. We observed a dose-dependent increase in myosin regulatory light chain phosphorylation in the right ventricle and a decrease in the right atrium. In the atria, both active and passive tensions were reduced, while no significant alterations were found in the right ventricle. However, a dose-dependent slowing of the action potential was found in both atrial and ventricular myocardium. Both the right atrium and right ventricle demonstrated responses to lead exposure; however, there was a mismatch between the alterations observed in atrial and ventricular parameters. These findings suggest that the atrial and ventricular myocardium adapt differently to lead exposure, with their responses varying depending on the specific dosage of lead consumed.