Cardiovascular Toxicology最新文献

Aluminum phosphide (ALP) is a highly toxic pesticide endangering the healthcare system. Higher central venous pressure (CVP) values may be linked to poorer outcomes in various medical conditions. This study evaluated the role of CVP and mean arterial pressure (MAP)/CVP ratio as prognostic factors for intensive care unit (ICU) admitted acute ALP-poisoned patients. This retrospective study included 145 acutely ALP-poisoned patients who were referred to the ICU during two years. Data regarding history, clinical manifestations, laboratory investigations, and outcome were collected and stratified by quartiles (Q1-Q4) of the measured CVP during the first 6 h after admission. In-hospital mortality and need for mechanical ventilation (MV) were significantly predominant in Q3 and Q4 groups of CVP levels (89.4% and 92% & 91.5% and 96%, respectively) (p-values < 0.001). After vasopressors administration, survivors demonstrated a significant mean reduction in CVP measurements (-4.5 mmHg), whereas non-survivors had a mean increase (+ 0.6 mmHg) (p = 0.011). MAP/CVP ratio has good discriminatory power (the areas under the curve (AUCs) = 0.836 and 0.846) for predicting the need for MV and in-hospital mortality, respectively. The CVP measurement (AUCs = 0.812 and 0.782, respectively) comes in second, followed by the poisoning severity score (AUCs = 0.778 and 0.768, respectively). There was a significant decrease in survival probability in patients with CVP ≥ 25 mmHg, and MAP/CVP ratio ≤ 2.48 (p-values < 0.001). Lower MAP/CVP ratios and higher CVP measurements are alarming signs, warranting a higher risk of the need for MV and in-hospital mortality in acute ALP poisoning.

Osimertinib, a third-generation epidermal growth factor receptor (EGFR) inhibitor, was developed to overcome resistance from EGFR-mutant non-small-cell lung cancer (NSCLC). While it offers significant therapeutic benefits, reports have linked Osimertinib to cardiotoxic effects. This study aims to clarify the direct cardiotoxicity of Osimertinib by reviewing clinical trials and cohort studies involving Osimertinib monotherapy compared to other EGFR inhibitors. A search was conducted in online databases. Measured outcomes included risk of heart failure (HF), myocardial infarction (MI), decline in left ventricular ejection fraction (LVEF), arrhythmias, and pericardial effusion. These outcomes were reported as risk ratio (RR) with a random effects model using 95% confidence intervals (CI). Five studies with 19,008 patients (age 68 ± 13, 65% female) were selected. Osimertinib therapy was associated with an increased risk of HF (RR = 1.45, 95% CI 1.19-1.76, p = 0.0002), decline in LVEF (RR = 3.10, 95% CI 1.72-5.59, p = 0.0002) and MI (RR = 1.40, 95% CI 1.09-1.79, p = 0.0078) compared to other EGFR inhibitors. There was no difference in the risk of arrhythmias and pericardial effusion. Osimertinib therapy is associated with an increased risk of HF and a decline in LVEF compared to other EGFR inhibitors, while associations with MI and arrhythmias were less consistent. Although these events are infrequent, their potential severity warrants proactive cardiac monitoring for patients receiving Osimertinib, particularly in patients with pre-existing risk factors.

Heart failure (HF) is a major cause of morbidity and mortality, and current therapies do not fully prevent adverse remodeling. Traditional Chinese medicine (TCM) formulas are increasingly explored as adjunctive strategies for HF; however, their efficacy and mechanisms require further validation. This study investigated whether Jinxinkang granule (JXK), a clinically used TCM formula, protects against pressure overload-induced HF in mice, and further explored the molecular mechanisms underlying its cardioprotective effects. Pressure overload HF was induced by transverse aortic constriction (TAC) in male C57BL/6J mice. Animals were randomized into control, model, JXK (low, medium, high dose), or positive control (trimetazidine) groups. Cardiac function was assessed by echocardiography, serum biomarkers (NT-proBNP, CK-MB, cTnT) were measured, and cardiac remodeling was assessed by hematoxylin and eosin staining, Masson's trichrome staining, wheat germ agglutinin staining, and TUNEL assay. Expression of senescence markers (p16, p53, MMP3) and cGAS-STING pathway components was analyzed by qPCR, Western blotting, and immunofluorescence. TAC induced systolic dysfunction, ventricular dilation, cardiomyocyte hypertrophy, fibrosis, and increased apoptosis, accompanied by activation of senescence markers and of cGAS-STING signaling. JXK dose-dependently improved left ventricular ejection fraction and fractional shortening, reduced serum injury biomarkers, attenuated cardiomyocyte hypertrophy and fibrosis, and decreased TUNEL-positive cells. Mechanistically, JXK suppressed TAC-induced upregulation of p16, p53, and MMP3, and inhibited cGAS, STING, p-TBK1, and p-IRF3 activation. JXK preserves cardiac function and attenuates remodeling in pressure overload-induced HF, potentially through inhibition of myocardial senescence and suppression of the cGAS-STING pathway.

Existing research data show that pulmonary artery smooth muscle cells (PASMCs) can play a very important role in the occurrence and development of pulmonary hypertension (PAH). Through in-depth study and analysis, we found that glioma-associated oncogene family zinc finger 1 (GLI1) has a significantly higher expression level in the nucleus and cytoplasm of hypoxic PASMCs. Next, GLI1 overexpression plasmid or small interfering RNA were transfected into hypoxic PASMCs respectively, and GLI1 promoted the migration and pyroptosis of hypoxic PASMCs, while GLI1 silencing had the opposite effect. Next, histone deacetylase 1 (HDAC1) was verified to be a binding protein of GLI1, and GLI1 promotes HDAC1 protein expression. Then, HDAC1 promoted abnormal of hypoxic PASMCs, while HDAC1 knockdown inhibited cell migration and pyroptosis. Then, the hypoxic PASMCs were transfected si-GLI1 alone or together with HDAC1-OE, and further confirm that GLI1 promotes hypoxia induced pyroptosis and abnormal proliferation of PASMCs by upregulating HDAC1 protein expression. In addition, we constructed a PAH rat model, and found that GLI1 silenced PAH rats had reduced expression of markers related to pyroptosis and smooth muscle cell proliferation in the lung tissue, and the lung injury of rats was reduced, and the lung function was significantly improved, suggesting that GLI1 silencing is beneficial to PAH in rats.

Electronic cigarettes (e-cigs) are major contributors to inflammatory-mediated responses, which are implicated in a vast array of pathophysiological conditions, including cardiovascular disease (CVD). More recently e-cigs have been recognized as a source of thirdhand exposure (THEC); the process by which expelled toxins settle on materials (i.e., carpets, curtains, clothes etc.) and undergo chemical reactions, rendering them more harmful overtime. Herein, mice were exposed to THEC for four months, and platelet reactivity, systemic mediated effects on platelet function, and cytokine expression profiles were analyzed in both sexes. Our data revealed a hyperactive platelet phenotype as determined by shortened bleeding and occlusion times, enhanced platelet aggregation, and dense granule secretion with no significant difference between males and females. Cytokines, amongst other inflammatory molecules, are well documented mediators by which platelet function is modulated and they also enhance susceptibility to CVD. To this end, and to elucidate the mechanism by which platelet reactivity was augmented, washed platelets that were exposed only to clean air (CA) and resuspended in THEC exposed plasma, displayed significantly increased platelet aggregation, dense granule secretion, and p-selectin expression. Indeed, this data suggests that THEC exposure elicits a systemic effect, enhancing platelet response, and was further validated by a dysregulated cytokine profile using plasma, free of platelets, in a sex-dependent manner. Collectively and for the first time, we highlight that both males and females are at similar risk of THEC-mediated prothrombotic phenotype, which is underlined-at least in part- by an indirect systemic effect of exposure on platelet reactivity that involves changes in the cytokine profile. These findings underscore this form of exposure as a threat to cardiovascular health.

Major adverse cardiovascular events (MACE) in patients with liver cancer receiving vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKI) remain uncertain. This retrospective cohort study aimed to evaluate the association between VEGF-TKIs and MACE and develop a risk prediction score. Using the Taiwan Cancer Registry linked with the Taiwan National Insurance Claim Database, 11,960 VEGF-TKI users were matched to 11,960 non-users by age and sex. Cause-specific hazard ratios (HRs) were estimated using multivariable Cox models with competing risk of non-cardiovascular death; propensity score (PS)-adjusted or PS-matched models were additionally conducted. During follow-up, the incidence of MACE was 49.5 versus 28.3 per 1,000 person-years in VEGF-TKI users and non-users. VEGF-TKI use was associated with increased MACE risk in multivariable analysis (adjusted HR 1.31; 95% CI 1.14-1.50); however, PS-adjusted and PS-matched models show non-significant associations. Because proportional hazards assumptions were violated, a 60-day landmark analysis was conducted, in which the increased risk was again significant across analytic approaches, including multivariable adjusted (HR 1.92; 95% CI 1.63-2.27), PS-adjusted (HR 1.35; 95% CI 1.00-1.82) and PS-matched models (HR 1.30; 95% CI 1.03-1.63). A point-based score was developed using a multivariable sub-distribution hazard model and assessed by a time-dependent c-index. The score demonstrated good discrimination with c-indices of 79.9% (3 months) and 74.2% (6 months). VEGF-TKIs were associated with increased risk of MACE among liver cancer patients. Landmark analyses indicated a persistently elevated risk among patients surviving beyond early treatment. A risk score based on prior cardiovascular history may help identify high-risk patients.

Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication characterized by cardiac dysfunction, inflammation, oxidative stress, and mitochondrial impairment, with limited therapeutic options. Taurine, a naturally occurring amino acid with known anti-inflammatory and mitochondrial-stabilizing properties, may offer therapeutic benefits. However, its role in SICM is not well defined. This study aimed to evaluate the protective effects of taurine against SICM and elucidate its underlying mechanisms. A murine model of SICM was established via cecal ligation and puncture (CLP), and AC16 cardiomyocytes were stimulated with lipopolysaccharide (LPS) to mimic septic injury in vitro. Cardiac function was assessed by echocardiography; inflammatory cytokines and cardiac injury markers were measured via ELISA. Mitochondrial integrity and function were evaluated using transmission electron microscopy (TEM), oxygen consumption rate (OCR), and mitochondrial membrane potential (MMP). Apoptosis was analyzed by TUNEL staining, flow cytometry, and Western blot. Rescue experiments using an NF-κB activator were conducted to validate pathway involvement. The results showed that taurine treatment significantly improved cardiac function and survival rates in SICM mice, attenuated myocardial inflammation and oxidative stress, restored mitochondrial structure and function, and suppressed apoptosis. These beneficial effects were reversed upon NF-κB activation, indicating that taurine exerts its cardioprotective role primarily through inhibition of the NF-κB signaling pathway. In conclusion, this study provides the first evidence that taurine protects against SICM by alleviating NF-κB-driven inflammation, oxidative stress, mitochondrial dysfunction, and apoptosis, suggesting its potential as a therapeutic agent for sepsis-induced cardiac injury.

Metal-on-metal (MoM) joint replacements were designed to improve durability in younger, active patients. However, cobalt-induced cardiomyopathy (CIC) has emerged as a rare but serious complication, often misattributed to idiopathic or ischemic causes. We systematically reviewed published case reports, case series, and laboratory studies describing CIC in patients with MoM implants. Data extraction included clinical presentation, diagnostic criteria, treatment, and outcomes. Methodological quality and risk of bias were assessed qualitatively. Eighteen cases were included. Implant wear and corrosion released systemic cobalt, which localised in myocardial tissue. Pathophysiological mechanisms included mitochondrial dysfunction, oxidative stress, impaired calcium handling, and apoptotic injury. Patients commonly presented with non-specific cardiac symptoms such as fatigue, dyspnoea, orthopnoea, arrhythmias, and heart failure, alongside extra-cardiac features including hearing loss, thyroid dysfunction, and neurocognitive changes. Diagnostic confirmation required serum cobalt levels typically exceeding 30-100 µg/L, with cardiac MRI demonstrating non-ischemic fibrosis and oedema. Chelation therapy reduced cobalt burden but was rarely effective alone. Revision of the MoM implant consistently led to clinical improvement when performed early; delayed intervention was associated with irreversible myocardial damage and poorer outcomes. CIC is an under-recognised but potentially reversible form of cardiomyopathy. Routine cobalt screening and early implant revision are essential to prevent progression to heart failure or sudden cardiac death. Multidisciplinary collaboration between cardiology and orthopaedics is critical for the timely diagnosis and management of these conditions.