搜索结果：Cardiovascular toxicology

Rhododendron molle, a member of the Ericaceae family, is a well-known medicinal plant in traditional Chinese medicine and ethnomedicine known as Yangzhizhu. As an important botanical drug, R. molle is characterized by "efficacy-toxicity duality". This review aims to provide a comprehensive and up-to-date overview of R. molle, encompassing its traditional medicinal uses, clinical applications, phytochemistry, pharmacology, toxicology, pharmacokinetics, and quality control in recent years. Information on R. molle was collected from scientific journals, classical books on traditional Chinese herbal medicine, and reports through library and electronic searches (PubMed, Google Scholar, Web of Science, CNKI, and other authoritative databases. R. molle is distributed in regions of China, and is used for treating pain, rheumatoid arthritis, cardiovascular disease, and gastrointestinal disorders. Approximately 349 chemical metabolites have been identified from R. molle, including diterpenoids, triterpenoids, flavonoids, lignans, and other metabolites. Among these metabolites, diterpenoids are recognized as the main bioactive metabolites, showing significant analgesic, anti-inflammatory, immunomodulatory, and cardiovascular effects. However, it is important to note that R. molle exhibits neurotoxicity, cardiotoxicity, hepatotoxicity, with its toxicity being linked to its primary diterpenoids. Rhodojaponin II and rhodojaponin III are generally selected as indicators for the quantitative determination of R. molle. Therefore, R. molle represents a valuable yet highly toxic botanical drug, while its traditional uses are supported by modern pharmacological evidence, further research is needed to clarify the mechanisms underlying its toxic effects and to establish scientific strategies for detoxification and quality control.

Microplastics and nanoplastics (MNPs) have been detected in human blood and cardiovascular tissues, raising concerns about their potential role in cardiovascular disease (CVD). However, the overall research landscape-including knowledge structure, collaboration networks, and evolving trends-remains poorly characterized. This study aims to map the field using bibliometric analysis. Publications from 2017 to 2025 were retrieved from the Web of Science Core Collection. Bibliometric analyses (publication trends, country/institution collaboration networks, keyword co-occurrence and clustering, co-citation networks, and burst detection) were performed using CiteSpace, VOSviewer, and Scimago Graphica. A total of 390 publications were analyzed. Annual publication output has grown exponentially since 2022. China, the United States, and Italy are the core contributing countries. Research hotspots center on inflammatory responses, oxidative stress, and pollutant exposure. The frontier has shifted from fundamental toxicology toward nanoplastics and specific polymers (e.g., polystyrene) in CVD, as well as their association with clinical outcomes. Emerging foci include cardio-renal comorbidity. To our knowledge, this is the first bibliometric study to systematically map the MNP-CVD research field. The field is moving from mechanistic exploration toward clinical epidemiological research. Future priorities include interdisciplinary collaboration, standardized detection methods, large-scale prospective cohort studies, and mechanism-based targeted interventions. Bibliometric data reflect publication patterns, not causal evidence.

Cardiovascular diseases and their major metabolic risk factors remain the leading contributors to morbidity and mortality in Europe. Despite the growing burden of cardiometabolic conditions and the critical role of early-phase research in drug development, the landscape of Phase I clinical trials in this therapeutic area has not been systematically explored in Europe. We analysed Phase I clinical trials registered on ClinicalTrials.gov from inception to December 2024, focusing on five European countries (France, Germany, Italy, Spain, and the United Kingdom). After applying disease-specific filters and excluding duplicates, device and dietary supplement studies, 488 trials were retrieved. Conditions were classified into 12 ICD-11-based disease groups and into two macro-categories: cardiovascular diseases (CVDs) and cardiovascular risk factors (CVRFs). Of the 488 trials, 35% targeted CVDs and 65% CVRFs. Diabetes mellitus was the most frequently studied condition (48%), followed by obesity (9%) and heart failure (7%). Most trials (84%) were industry-sponsored, with seven companies accounting for one-third of studies. Germany and the United Kingdom conducted the most trials (262 and 170 trials), while Italy the fewest (20). Southern countries focused predominantly on CVDs, whereas northern countries more on CVRFs. Trials involving ATMPs and rare diseases were proportionally more common in Spain and Italy. Overall, 51% of studies enrolled healthy volunteers, though none in Italy. Significant geographic disparities and a declining trend in early-phase cardiometabolic research may weaken Europe's competitiveness in drug development. Strategic investments in infrastructure, regulatory harmonization, and public-private collaboration are needed to reverse the recent trend.

Peripherally restricted ('second-generation') cannabinoid CB1 receptor (CB1R) antagonists have been suggested to have therapeutic potential in numerous diseases. However, their effects on the cardiovascular system require further research. The peripheral CB1R antagonist AM6545 failed to modify the decrease in blood pressure (BP) elicited by inhibition of anandamide degradation in spontaneously hypertensive rats. The aims of the present study were to examine the effect of AM6545 on BP and its interaction with endocannabinoid-evoked effects in deoxycorticosterone acetate (DOCA)-salt rats. For this purpose, we applied methanandamide (MethAEA), a stable analogue of anandamide, and URB597, an inhibitor of its degradation, in urethane-anesthetized animals. AM6545 did not affect BP by itself. MethAEA elicited a biphasic effect (a rise in BP, followed by its fall); both phases were antagonized by AM6545. URB597 induced a monophasic hypotensive effect, which was abolished by AM6545 in DOCA-salt rats but further enhanced in control animals. AM6545 also unmasked an additional increase in BP after URB597 in both groups of rats. In conclusion, AM6545 modifies the cardiovascular effects of endocannabinoids in hypertension in a model-dependent manner. The cardiovascular effects of CB1R antagonists should be carefully evaluated when assessing their potential therapeutic significance, as they may unmask an increase in BP.

People with HIV (PWH) experience elevated cardiovascular disease risk compared to people without HIV. Stimulant use may further increase subclinical myocardial injury among PWH, but data on cardiovascular biomarkers, including serum high-sensitivity cardiac troponin T (hs-cTnT) in this population is limited. This cross-sectional secondary analysis included 72 cisgender men with and without HIV enrolled in a South Florida cohort. Stimulant exposure was defined as any non-prescribed stimulant use in the past 3 months and/or a reactive urine toxicology screen, creating four HIV-by-stimulant use groups (i.e., HIV+Stim&#x2009;+&#x2009;, HIV+Stim-, HIV-Stim&#x2009;+&#x2009;, and HIV-Stim-). hs-cTnT was measured using a Roche high-sensitivity assay, with values below the limit of detection treated as undetectable. We used a two-part model (logistic for detectability; log-normal among participants with detectable hs-cTnT), adjusted for age and recent tobacco use, with sensitivity analyses adding renal function and cardiometabolic factors. After adjusting for age and recent tobacco use, HIV+Stim+ participants had higher odds of detectable hs-cTnT (aOR = 7.48, 95% CI: 1.25, 44.62) and higher estimated mean concentration of hs-cTnT (&#x3b2;&#x2009;=&#x2009;0.51, p&#x2009;=&#x2009;0.031, mean&#x2009;=&#x2009;12) than the HIV-Stim- group. Exploratory analyses suggested a positive dose-response association between amphetamine metabolite levels and hs-cTnT (r(11) = 0.86, p&#x2009;<&#x2009;0.0001). Co-occurring HIV and stimulant use were associated with higher hs-cTnT in this sample. However, given that hs-cTnT may reflect a range of acute, subacute, and chronic processes, and the small sample size and restricted generalizability, these findings should be interpreted as exploratory and hypothesis-generating and require confirmation in larger studies.

Cardiovascular diseases (CVD) remain the leading global cause of morbidity and mortality, driven in part by dysregulated redox homeostasis and chronic inflammation. Superoxide dismutase (SOD), a key enzymatic defence against reactive oxygen species (ROS), plays a central role in maintaining cardiovascular integrity through regulation of oxidative stress across cytosolic (SOD1), mitochondrial (SOD2) and extracellular (SOD3) compartments. Impairment of SOD function contributes directly to endothelial dysfunction, myocardial injury and vascular remodelling. Curcumin (Cur), a pleiotropic polyphenol derived from Curcuma longa, has emerged as a potent modulator of SOD activity and expression. Evidence from preclinical models consistently demonstrates that Cur enhances SOD-dependent antioxidant defences, thereby attenuating oxidative damage, inflammation, apoptosis and fibrosis across multiple CVD contexts, including myocardial infarction, cardiomyopathy, hypertension and diabetic complications. While Cur also influences additional signalling pathways, such as NF-&#x3ba;B, PI3K/AKT and Nrf2, these effects are increasingly understood to converge on SOD-mediated redox regulation. Recent advances in nanodelivery systems have further improved Cur bioavailability and its capacity to modulate SOD activity in&#xa0;vivo. However, despite robust preclinical evidence, clinical validation remains limited. This review synthesizes current mechanistic and translational evidence, positioning SOD as the central mediator of Cur's cardioprotective effects and highlights key gaps in clinical translation.

Deltamethrin is a commonly applied pyrethroid insecticide; however, its relationship with the risk of coronary heart disease (CHD) remains unclear. Given its widespread residues in the environment and food, and the growing concern over its long-term cardiovascular effects, it is of public health importance to determine whether and how deltamethrin exposure contributes to CHD. This study integrated data from the Global Burden of Disease study (GBD 2021) and Mendelian randomization (MR) to assess causality. Utilizing transcriptomic data associated with CHD and the predicted targets of deltamethrin, core genes were identified through weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, and machine learning, pinpointing SPI1, IL1B, ICAM1 and FCER1G. These genes were enriched in immune-inflammatory pathways, associated with a pro-inflammatory microenvironment, and showed specific expression in monocytes. Molecular docking and dynamics simulations confirmed stable binding of deltamethrin to these targets. In vitro experiments demonstrated that deltamethrin dose-dependently inhibited cell viability, induced oxidative stress, and upregulated the expression of the core genes. In conclusion, deltamethrin may increase the risk of CHD, possibly by disrupting the immune-inflammatory networks involving SPI1, IL1B, ICAM1 and FCER1G, providing novel insights into the cardiovascular toxic effects of pyrethroids.

This study integrates multidimensional computational approaches-network toxicology, machine learning, molecular docking, and molecular dynamics simulation-to systematically elucidate the toxic mechanism by which the environmental pollutant diisononyl cyclohexane-1,2-dicarboxylate (DINCH) contributes to atherosclerosis. By jointly mining multiple databases, we obtained 246 targets common to DINCH and atherosclerosis. LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) then identified 8 significantly upregulated core targets (CSF1R, CD36, CCL3, CCR2, ADAM8, TLR1, CTSS, and MMP1). Functional enrichment analysis showed that these core targets were significantly associated with key signaling pathways, including lipid and atherosclerosis, the PPAR signaling pathway, the PI3K-Akt signaling pathway, and the AGE-RAGE signaling pathway in diabetic complications. Differential gene analysis confirmed that these genes were significantly upregulated in diseased tissues, and receiver operating characteristic (ROC) analysis demonstrated excellent diagnostic performance (AUC = 0.87-0.96). Immune cell infiltration analysis further revealed a strong association between the core targets and immune cell populations, notably macrophages and T cells. Molecular docking and molecular dynamics simulations showed that DINCH had high affinity for the core targets, and its binding to CCR2 was the most stable (binding free energy = -7.6 kcal/mol). The final AOP framework systematically presented the cascade by which DINCH may contribute to atherosclerosis through metabolic disruption and immune activation. This study provides new mechanistic insights into the development of DINCH-induced atherosclerosis and offers a theoretical basis for health risk assessment of environmental pollutants.

White mulberry (Morus alba L.) leaves have traditionally been used to improve glycemic control in diabetic and prediabetic individuals; however, their effects in hypertension remain insufficiently characterized. This study evaluated the impact of dietary mulberry leaf supplementation on blood biochemical parameters and on renal, cardiac, and vascular outcomes in spontaneously hypertensive rats (SHR). In addition, the content of the key bioactive compound 1-deoxynojirimycin (DNJ) was quantified. Male SHRs, aged 4 months (n=10 per group), were assigned to receive either standard rat chow or chow supplemented with ground mulberry leaves (7% w/w; ~4.0 g/kg body weight; 1.46&#xb1;0.07 mg DNJ/rat/day) for eight weeks. Mulberry leaves contained 1.15&#xb1;0.01 mg DNJ/g dry weight, as determined by RP-HPLC-DAD. Supplementation significantly reduced glycated hemoglobin (HbA1c: 2.23% vs. 1.98%, p=0.021) and attenuated postprandial glucose elevation during oral glucose tolerance testing (112 vs. 94 mg/dL at 120 min, 0.85-fold; p=0.005). No significant effects were observed on renal, cardiac, or vascular biomarkers, as assessed by ELISA and standard blood analyses. Kidney histology, including vascular thickness and density, was unchanged. Vascular reactivity to acetylcholine and noradrenaline did not differ between groups, and no differences were detected in the isolated perfused heart model. These findings suggest a potential role for Morus alba leaves in dietary strategies targeting glucose regulation in hypertension and underscore the need for longer-term and translational investigations.

暂无摘要（点击查看详情）

Despite the increasing burden of mortality due to cardiovascular disease, the traditional risk factors fail to explain the complexity of the pathology of cardiovascular disease, especially in the context of chronic inflammation. Emerging scientific evidence indicates that dysbiosis of the oral, gut, and reproductive microbiome is associated with systemic vascular dysfunction. This review comprehensively discusses the available scientific data on the interactions between the mucosal colonizing microbiota and their modulation of whole-body inflammation and cardiovascular disease pathogenesis. It underlines the roles of microbial metabolites, including trimethylamine N-oxide and lipopolysaccharides, in immune activation, epithelial barrier cell injury, and their effects in endothelial activation, vascular remodeling and dysfunction, oxidative stress, and inflammation. This review describes the mechanistic interplay that drives atherosclerosis and vascular dysfunction, mediated by immune activation and cytokine-driven inflammatory cascades. Sex hormones influence the composition of the microbiota and the host immune responses, thereby influencing vascular disease manifestations and responses to therapy. These mechanisms present the potential of intervening at the microbial crossroads through microbiome-targeted approaches as an effective treatment strategy for cardiovascular disease.

Evidence-based medicine (EBM) skills are fundamental to lifelong learning. These can be tracked the same way that procedural skills are tracked-via residency program logs. Review of the logs can inform faculty on the EBM activity of their trainees. An understanding of the topics residents query while on shift can provide insight into where they need further knowledge to provide optimal patient care. Our objective in this project was to categorize the relationship of the clinical questions posed by emergency medicine (EM) residents while working in the emergency department to the American Board of Emergency Medicine (ABEM) Model of Clinical Practice. We conducted this institutional review board-approved study (deemed exempt research) in a postgraduate year (PGY) 1-4 EM residency. A toxicology rotation and fellowship were established during the study period. Residents were required to submit three to five descriptions of EBM activity per 28-day EM rotation block into the program's management software. We analyzed each complete log submitted from June 2013-May 2020 using the 2019 ABEM Model of Clinical Practice. The clinical questions posed were mapped to the ABEM Model for content, including sub-categories and acuity level. Demographic information in the logs allowed for analysis for ABEM's pediatric and geriatric modifiers. The primary outcome measure was the number of clinical questions mapped to each section of the Model. From June 2013-May 2020, 10,444 discrete completed logs were completed by 137 residents. "Procedures and Skills" (n = 1,110, 10.63%) and "Cardiovascular Disorders" (n = 991, 9.49%) were the most prevalent ABEM content areas. "Trauma" (n = 812, 7.77%) and "Drugs and Chemical Classes" (n = 749, 7.17%) were the most prevalent ABEM sub-categories. "Emergent" (n = 7,770, 74.3%) was the most commonly searched ABEM acuity, followed by "lower acuity" (n = 5,341, 51.1%) and "critical" (n = 5,192, 49.7%). Of note, not all conditions have ABEM acuity codes, and some have multiple. Clinical questions addressed issues regarding pediatric patients in 10.16% (n = 1,061) and geriatric patients in 8.05% (n = 841) of logs. In this single-site cohort, "Procedures and Skills" was the most common source of on-shift questions for EM residents, perhaps representing just-in-time training. "Trauma" was the most common sub-category, potentially the result of a large footprint in the ABEM Model of Clinical Practice. The residency program's toxicology rotation and fellowship may have influenced the types of conditions treated by residents and the subsequent content of their logs. Furthermore, completing logs on shift may have impacted the mapping to ABEM acuity levels. Programmatic understanding of residents' on-shift, evidence-based medicine questions could serve to identify educational gaps and opportunities.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse cardiometabolic outcomes. But the molecular mechanism is still unexplored. The purpose of our study is to investigate the relationship between exposure to PAHs and cardiometabolic dysfunction, and to explore the mechanism and molecular pathways. We combined National Health and Nutrition Examination Survey (NHANES) data with multiple toxicological databases. Mendelian randomization (MR) was used to evaluate the causal contribution of immune factors to cardiovascular diseases (CVD) and metabolic disorders. Network toxicology and molecular docking were conducted to identify candidate molecular targets and signaling pathways involved in PAHs-related cardiometabolic dysfunction. Higher PAHs exposure was associated with increased cardiometabolic index (CMI) in adults, and this association was partially mediated by monocyte percentage and white blood cell count. MR analyses supported a causal role of these immune-related factors in CVD and metabolic disorders. Network toxicology and molecular docking involved pathways including chemical carcinogenesis-receptor activation, chemical carcinogenesis- DNA adduct formation, cytochrome P450 metabolism, and steroid hormone biosynthesis. CYP1A1, ESR1, and MAO were identified as potential key targets. Changes in monocyte percent and white blood count may help explain how PAH exposure is linked to cardiometabolic dysfunction. The implicated pathways and targets provide potential mechanisms. Our findings provide epidemiological and mechanistic evidence suggesting that PAH exposure may be linked to adverse cardiometabolic outcomes, potentially through immune-related pathways.

Extreme heat exposure leads to excess cardiovascular morbidity and mortality among older adults, but misalignment in the geographic scales of health data and intraurban heat exposure make it challenging to inform local interventions. We introduce an adaptable framework for developing health burden estimates at finer geographic scales by connecting small area analysis (SAA) techniques with an epidemiologic model of heat related health risks in three steps: (a) estimating an exposure response function using individual level cardiovascular disease (CVD) hospitalizations for adults aged 65 and over; (b) downscaling daily CVD hospitalization incidence rates at the ZCTA-level to census block groups (CBG) using SAA, adjusting for individual- and community-level demographic factors, and (c) linking exposure-response with daily incidence rates to estimate heat-attributable burden at the CBG scale. Using the data for a metropolitan area in the southeastern United States for the summer of 2018, we estimated 1.8 to 22.0 excess hospitalizations per 10,000 people across CBG. We demonstrate the utility of this 3-step approach to help inform localized intervention strategies by classifying neighborhoods as one of four risk groups: Low, Health-driven, Heat-driven, and Dual-channel (driven by both heat and health). In comparison, using coarse-resolution temperature resulted in a significantly smaller heat-attributable health burden with different geographic distribution across the CBGs, highlighting the importance of using appropriately scaled exposure data. The findings from this study can support more effective heat interventions to address heat-health related outcomes, rather than exposure alone. Exposure to hot temperatures can result in health issues, especially for older adults. These health issues can be avoided by modifying the physical environment to make temperatures cooler and implementing policies that help people avoid dangerous temperatures. However, data on health outcomes is often not available at the same geographic scale as temperature, making it difficult for policymakers to identify places where interventions are most needed. In this study, we introduce an approach to align the geographic scale of temperature and health data and estimate neighborhood&#x2010;level heat&#x2010;related health outcomes. We demonstrate how this approach works using data from a metropolitan area in the Southeastern United States. During the summer of 2018, we estimated that there were 163 excess cardiovascular disease (CVD) hospitalizations due to high temperatures among older adults, although the rate of heat&#x2010;related hospitalizations varies by neighborhood. Nearly one&#x2010;third of older adults live in areas with high rates of CVD and high temperatures, which result in above&#x2010;average heat&#x2010;attributable health burden in these neighborhoods. We find that using less detailed temperature data changes the results. The findings from this study can help local decision makers identify the most effective approaches for preventing heat&#x2010;related health issues.

While air pollution is a recognized cardiovascular risk, its specific impact on aortic stenosis (AS) remains poorly characterized. This study investigates the association between air pollution and incident AS, integrating gene-environment interactions and network toxicology. Based on the UK Biobank as the primary cohort, long-term air pollution exposure&#xa0;(per standard deviation&#xa0;increase) is associated with an increased risk of&#xa0;AS, with HRs and 95% CIs of 1.60 (1.55,1.66) for PM2.5, 1.37 (1.32, 1.41) for PM10, 1.37 (1.32, 1.42) for NO2, and 1.36 (1.31, 1.41) for NOx. The observed associations demonstrate high consistency across a suite of advanced internal methodological validations and are further replicated in the Tianshan Community Cohort. There are joint and interactive effects of genetic susceptibility and air pollutants on AS risk. Network toxicology and bioinformatics analyses reveal key PM-AS target genes enriched in the lipid and atherosclerosis, fluid shear stress and atherosclerosis, and IL-17 signaling pathway. In conclusion, long-term exposure to PM2.5, PM10, NO2, and NOx is significantly associated with an increased AS risk, with a potential interaction between environmental exposure and genetic susceptibility.

Fine particulate matter (PM2.5), as a widespread environmental pollutant, is closely associated with cardiovascular diseases. The adverse effects of PM2.5 on the cardiovascular system and the molecular mechanisms driving PM2.5-aggravated atherosclerosis remain incompletely understood. In this study, in vivo and in vitro PM2.5 exposure models were established to explore the relevant pathogenic mechanisms. Male ApoE&#x207b;/&#x207b; mice were randomly divided into three groups: filtered air(FA) group, unfiltered air(UA) group, and concentrated PM2.5 air(CA) group. For in vitro experiments, mouse aortic vascular smooth muscle cells were exposed to PM2.5 at concentrations of 0, 25, 50, and 100&#x202f;&#x3bc;g/ml, meanwhile,group control was set up, DRP1 inhibitor Mdivi-1 and ferroptosis inhibitor Fer-1 were used to intervention, and PINK1 knockdown cell model was constructed. Aortic vascular function was evaluated via ultrasonography after exposure. Histopathological changes, collagen deposition, and lipid accumulation in arterial tissues and cells were evaluated via HE staining, Masson staining, Oil Red O, and BODIPY staining, respectively. Immunofluorescence and Western blot were applied to analyze the expression of related proteins in the arterial wall. The results demonstrated that PM2.5 exposure accelerated atherosclerosis progression and VSMC phenotypic switching.PM2.5 exposure upregulated mitochondrial fission proteins and downregulated fusion proteins, with DRP-1 as a critical regulatory molecule. PM2.5 specifically activated PINK1/Parkin-mediated mitophagy rather than the FUNDC1 pathway. PINK1 knockdown markedly attenuated pro-ferroptotic signaling. Mdivi-1 intervention alleviated PM2.5-induced excessive mitophagy, upregulated pro-ferroptotic signaling and phenotypic switching of VSMC. Fer-1 treatment also efficiently inhibited VSMC phenotypic switching.The results of this study demonstrate that DRP1-driven PINK1/Parkin- mediated mitophagy and inducing pro-ferroptotic signaling to promote the phenotypic switching of VSMCs in PM2.5-aggravated atherosclerosis, These findings provide new insights into the pathogenesis of environmental atherosclerosis and potential targets for therapeutic intervention.

Since Ephedra Herba (ephedra) and its major alkaloid ephedrine were prohibited as dietary supplements due to their adverse effects on the cardiovascular and central nervous system (CNS), most studies have focused on their amphetamine-like effects and neurotoxicity. However, ephedra also has a long history of use in the treatment of various CNS diseases (known as "Zhong Feng" syndrome) according to two thousand years of traditional Chinese medicine (TCM) records. Pharmacokinetic reports have also demonstrated that alkaloids of ephedra can quickly penetrate the blood-brain barrier (BBB) once absorbed into the blood and there are multiple alkaloids derived from ephedra which have been identified as natural sympathomimetic drugs. These drugs are capable of interfering with several types of neurotransmitter, and have an especially potent effect on monoamine neurotransmitters. The effects of ephedra on CNS therefore remain both contradictory and confusing. In this review, we summarized the available evidence of pharmacology and toxicology of ephedra and ephedrine on CNS, and aimed to clarify their effects. Given the unmet need for more efficient treatments of neurological disorders, ephedra is potentially valuable herbal medicine which may provide a promising avenue for development of treatments and encourage further drug research and development (R&D).

Thyroid dysfunction has been associated with adverse postoperative outcomes, but little is known about its effects on patients undergoing coronary artery bypass grafting (CABG). Here, our goals were (1) to evaluate the incidence of CABG in patients with hypothyroidism receiving thyroid hormone replacement therapy, and (2) to assess short-term and long-term outcomes in patients with hypothyroidism undergoing CABG compared with controls without thyroid disease, and (3) to determine whether abnormal preoperative thyroid-stimulating hormone (TSH) levels modify postoperative surgical risk in this patient population. Retrospective longitudinal study using the TriNetX Global Collaborative Network database. The incidence of CABG was evaluated in about 1.23 million patients with hypothyroidism during a 20-year observation period (median of 4.4 &#xb1; 5.9). Post-CABG outcomes, including mortality, cardiovascular events, and postsurgical complications, were evaluated in 6557 patients with hypothyroidism over 10 years after 1:1 propensity score-matching. Over 20 years, patients with a diagnosis of hypothyroidism had a higher incidence of CABG compared with controls (0.27% vs. 0.22%; hazard ratio [HR] 1.08; confidence interval [CI]: 1.03-1.14). Among patients who underwent CABG, the diagnosis of hypothyroidism was associated with mild increased risk of short-term postsurgical infections (HR:1.10, CI:1.01-1.20), CABG-specific complications (HR: 1.24, CI: 1.08-1.42), and critical care utilization (HR:1.14, CI:1.07-1.21). During long-term follow-up, these patients were at increased risk of incident heart failure (HR:1.15, CI:1.04-1.28), stroke (HR:1.18, CI:1.01-1.39), and major adverse cardiovascular events (MACE) (HR:1.15, CI:1.01-1.29). Sensitivity analysis, including only patients with hypothyroidism diagnosis, showed that abnormal preoperative TSH levels, particularly those with elevated TSH, had a higher risk of short-term mortality and long-term embolic events. Hypothyroidism is associated with a higher incidence of coronary disease requiring CABG and increased risks of postoperative complications, heart failure, stroke, and MACE. These findings support the potential value of preoperative thyroid function assessment and optimization to mitigate postoperative complications and improve surgical outcomes in this high-risk group.

Methamphetamine (METH)-induced cardiomyocyte injury is the leading cause of mortality beyond acute intoxication. METH abuse often occurs in crowded, poorly ventilated environments, and even moderately high ambient temperatures exacerbate METH-related cardiovascular emergencies. However, the underlying mechanisms by which environmental factors drive the progression of cardiac diseases remain poorly understood. This study modeled the real-world scenario in vivo by exposing mice to METH under normothermic condition (NC, 22 &#xb0;C) or subthreshold thermal stress (STS, 28 &#xb0;C, a mild thermal challenge for mice) conditions, and in vitro by using H9c2 cardiomyocytes exposed to METH at 37 &#xb0;C or 39 &#xb0;C. STS significantly potentiated METH-induced cardiac dysfunction, mitochondrial ultrastructural damage, and oxidative stress (p < 0.05). Mechanistically, the co-exposure impaired mitochondrial respiratory chain complex I and led to excessive mitochondrial ROS (mtROS) production, activating the pro-apoptotic protein BAX, causing mitochondrial outer membrane (MOM) permeabilization and the cytosolic release of mitochondrial DNA (mtDNA). Cytosolic mtDNA-mediated NLRP3 inflammasome activation subsequently executed cardiomyocyte pyroptosis via caspase-1/Gasdermin D (p < 0.05). Crucially, the mitochondria-targeted antioxidant mitoquinone (MitoQ) substantially attenuated the aggravated cardiotoxicity by scavenging the initial mtROS (p < 0.05), thereby preventing the activation of the downstream BAX/mtDNA/NLRP3 axis. These findings provide evidence for a defined signaling basis for this drug-environment interaction and highlight mitochondrial redox modulation as a potential therapeutic strategy for psychostimulant-associated cardiovascular injury.