Cardiovascular Toxicology最新文献

{"title":"Trained Immunity as a Mechanistic Bridge Between Uremic Toxins, Atherosclerosis, and Vascular Calcification in Chronic Kidney Disease.","authors":"Junyan Zhang, Yitong Chen, Sibei Tao, Minggang Zhou, Chen Li, Li Rao, Yong He, Zhongxiu Chen","doi":"10.1007/s12012-026-10189-6","DOIUrl":"10.1007/s12012-026-10189-6","url":null,"abstract":"<p><p>Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD), largely driven by accelerated atherosclerosis and vascular calcification. These complications cannot be fully explained by traditional cardiovascular risk factors, indicating that CKD-specific mechanisms may contribute to persistent vascular inflammation. Trained immunity, a long-lasting functional reprogramming of innate immune cells mediated by metabolic and epigenetic remodeling, has emerged as a plausible mechanistic framework linking uremic toxin accumulation to cardiovascular injury. However, the level of evidence differs substantially across individual toxins. Indoxyl sulfate currently has the most direct evidence for classical trained immunity, whereas the evidence for p-cresyl sulfate, homocysteine, S-adenosylhomocysteine, and parts of trimethylamine N-oxide (TMAO) biology remains more indirect or hypothesis-generating. Uremic toxins may therefore act as endogenous danger signals that potentially prime monocytes, macrophages, and endothelial cells toward a hyper-inflammatory state. Because these trained phenotypes may be epigenetically durable, conventional dialysis and downstream anti-inflammatory therapies may be insufficient to reverse cardiovascular risk in CKD. This review summarizes the graded mechanistic evidence potentially linking uremic toxin-induced trained immunity to atherosclerosis and vascular calcification and discusses emerging therapeutic strategies targeting toxin burden, metabolic pathways, epigenetic remodeling, and myeloid-specific drug delivery. These approaches remain investigational in this setting, and evidence that they specifically modify uremic toxin-induced trained immunity in patients is currently lacking.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104674","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":"Intravenous Mitochondrial Injection Attenuates Methanol-Induced Cardiotoxicity Through Restoration of Mitochondrial Function and Suppression of Oxidative Stress.","authors":"Ahmad Salimi, Hanieh Delavari, Hamed Karroubian, Behrooz Elyasi, Mina Dehghanypoor, Elahe Zeynali, Salva Zaki, Zhaleh Jamali","doi":"10.1007/s12012-026-10199-4","DOIUrl":"10.1007/s12012-026-10199-4","url":null,"abstract":"<p><p>Methanol poisoning induces severe mitochondrial dysfunction through inhibition of mitochondrial respiration, excessive reactive oxygen species (ROS) generation and oxidative stress. The present study investigated whether injection of freshly isolated mitochondria, could attenuate methanol-induced cardiac mitochondrial dysfunction and oxidative damage in rat. Adult male Wistar rats were randomly allocated into five experimental groups: control, methanol, methanol plus single mitochondrial injection, methanol plus repeated mitochondrial injection (double) and mitochondria alone. Fresh functional mitochondria were isolated from healthy donor cardiac tissue and administered intravenously (250 µg/kg), 30 min after methanol intoxication. Serum cardiac injury biomarkers, including creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), were measured. Oxidative stress was evaluated by determining malondialdehyde (MDA) and glutathione (GSH) levels. Cardiac mitochondrial function was assessed by measuring succinate dehydrogenase (SDH) activity, mitochondrial swelling, mitochondrial ROS production, and mitochondrial membrane potential (MMP). Methanol intoxication significantly increased serum cardiac injury biomarkers, ROS generation, lipid peroxidation, and mitochondrial swelling while markedly reducing GSH content, SDH activity, and MMP compared with the control group. Mitochondrial injection significantly attenuated oxidative stress, decreased ROS production, restored antioxidant capacity, improved SDH activity, reduced mitochondrial swelling, and preserved MMP. Repeated mitochondrial administration showed relatively greater improvement than single administration, although no consistent dose-response relationship was observed. Also, histopathological examinations demonstrated significant recovery following mitochondrial injection. Fresh mitochondrial injection effectively ameliorated methanol-induced cardiotoxicity by reducing oxidative stress, preserving mitochondrial integrity, and restoring mitochondrial function in cardiac tissue. These findings suggest that mitochondrial injection represents a promising mitochondria-targeted therapeutic approach for methanol-induced cardiotoxicity.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104621","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":"Dexpanthenol Attenuates Doxorubicin-Induced Cardiotoxicity by Modulating Oxidative Stress, Inflammation, and Apoptosis.","authors":"Durmuş Ali Aslanlar, Mustafa Çelik, Mehmet Öz, Naile Kökbudak","doi":"10.1007/s12012-026-10194-9","DOIUrl":"10.1007/s12012-026-10194-9","url":null,"abstract":"<p><p>Doxorubicin (DOX)-induced cardiotoxicity converges on oxidative-nitrosative stress, TLR4/NF-κB-driven inflammation, and caspase-3-mediated apoptosis, and remains a major dose-limiting complication of anthracycline therapy. Dexpanthenol (DEX), a coenzyme A precursor, has shown anti-oxidative, anti-inflammatory, and anti-apoptotic activity in diverse organ-injury models, but its cardioprotective potential against DOX has not been systematically evaluated. The present study aimed to investigate the protective effects of DEX against DOX-induced cardiotoxicity in Wistar rats. Twenty-eight male Wistar rats were randomly allocated to four groups (n = 7): Control, DOX (single 25 mg/kg i.p. on day 1), DOX + DEX (DOX on day 1 followed by 500 mg/kg/day DEX for eight days), and DEX (500 mg/kg/day for eight days). TLR4, NF-κB p65, TNF-α, MDA, SOD, and GSH were quantified by ELISA in both serum and cardiac tissue; caspase-3 and GFAP were quantified in cardiac tissue. Cardiac TAS, TOS, OSI, NO, and iNOS were also measured. Myocardial sections were graded for seven histopathological parameters by a blinded pathologist. DOX produced a robust cardiotoxic phenotype, with elevations in inflammatory, oxidative, nitrosative, and apoptotic markers, depletion of antioxidant defenses, and marked histopathological injury. Co-administration of DEX attenuated TLR4/NF-κB/TNF-α signaling in both compartments, reduced caspase-3 and GFAP, normalized TAS and OSI, and significantly improved five of seven histopathological parameters after multiplicity adjustment. Protection was selective: cardiac SOD, GSH, NO, and total oxidant status were only partially restored, and inflammatory cell infiltration was unchanged. DEX exerts a partial but mechanistically coherent cardioprotective effect against DOX-induced cardiotoxicity, chiefly through attenuation of TLR4/NF-κB-driven inflammation and caspase-3 signaling. These findings support its evaluation as a multi-target adjunct in cardio-oncology.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104684","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":"Substrate-Dependent Pro- and Antiarrhythmic Action of Omecamtiv Mecarbil at the Ventricular and Atrial Level: Insights from a Langendorff-Perfused Rabbit Heart Model.","authors":"Julian Wolfes, Katharina Neff, Felix Wegner, Benjamin Rath, Florian Doldi, Lars Eckardt, Gerrit Frommeyer, Christian Ellermann","doi":"10.1007/s12012-026-10200-0","DOIUrl":"10.1007/s12012-026-10200-0","url":null,"abstract":"<p><p>Omecamtiv mecarbil is a cardiac-selective myosin activator and potential heart failure treatment, but its electrophysiological profile remains incompletely characterized. We investigated omecamtiv mecarbil in a Langendorff-perfused rabbit heart model. Forty-eight rabbit hearts were retrogradely perfused; twenty-four in a ventricular and twenty-four in an atrial setup. In the ventricular setup, action potential duration at 90% repolarization (APD₉₀), QT interval, and dispersion of repolarization were assessed during pacing at seven cycle lengths. After baseline recordings, Group 1 (n = 12) received 1, 5 and 10 µM omecamtiv mecarbil sequentially, while Group 2 (n = 12) received 100 µM sotalol followed by 5 µM omecamtiv mecarbil. In the atrial setup, Group 3 (n = 12) received 5 and 10 µM omecamtiv mecarbil, and Group 4 (n = 12) received isoproterenol/acetylcholine (IsoACh) to increase atrial fibrillation (AF) susceptibility, followed by 5 µM omecamtiv mecarbil. Omecamtiv mecarbil alone shortened ventricular APD₉₀ and QT interval, increased dispersion of repolarization, and raised ventricular arrhythmia incidence. Sotalol prolonged APD₉₀, QT interval, and dispersion, with a marked rise in VT episodes; additional omecamtiv mecarbil did not further prolong repolarization but increased arrhythmia susceptibility further. In the atrial setup, omecamtiv mecarbil alone prolonged conduction time and increased AF inducibility. Under IsoACh, which shortened atrial APD and refractoriness and increased AF episodes, additional omecamtiv mecarbil slowed atrial conduction and markedly suppressed AF. In summary, omecamtiv mecarbil was proarrhythmic at the ventricular level, particularly under reduced repolarization reserve, but showed antiarrhythmic effects in an IsoACh-induced AF model and proarrhythmic properties in the healthy atrium, indicating a substrate-dependent electrophysiological profile.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149073673","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":"Reduced ALDH2 Activity and Cardiovascular Carbonyl Stress: From Reactive Aldehyde Networks to Coronary Microvascular Obstruction.","authors":"Zhaoqi Yan, Xiangyi Pu, Yongyuan Cai, Qiaomin Wu, Xinai Zhang, Xing Chang, Jinfeng Liu, Yanli Wang, Zhiming Liu, Ruxiu Liu","doi":"10.1007/s12012-026-10201-z","DOIUrl":"10.1007/s12012-026-10201-z","url":null,"abstract":"<p><p>Primary percutaneous coronary intervention restores epicardial flow after ST-segment elevation myocardial infarction, but tissue perfusion may remain impaired. Coronary microvascular dysfunction, angiographic no-reflow, cardiac magnetic resonance-defined microvascular obstruction, and intramyocardial hemorrhage are overlapping but non-equivalent phenotypes. This review examines reduced mitochondrial aldehyde dehydrogenase 2 (ALDH2) activity as a susceptibility amplifier rather than an established independent cause of these outcomes. Reperfusion generates reactive oxygen species that initiate lipid peroxidation and produce electrophilic aldehydes, including 4-hydroxy-2-nonenal, malondialdehyde, and acrolein. Their effects are shaped by compartmental generation, competing clearance systems, protein-adduct persistence, and positive feedback between mitochondrial injury and inflammation. Methylglyoxal is considered a parallel, glyoxalase-dominant dicarbonyl pathway rather than a principal ALDH2 substrate. The resulting network may impair endothelial nitric oxide signaling and barrier integrity, promote platelet activation and neutrophil extracellular trap formation, and increase cardiomyocyte edema and damage-associated molecular-pattern release. Pericyte constriction contributes to experimental no-reflow, whereas pericyte sensitivity to 4-hydroxy-2-nonenal remains a theoretical hypothesis awaiting direct experimental confirmation. We also assess adductomics, proteomics, lipidomics, and time-resolved sampling strategies. Free aldehydes are chemically and preanalytically unstable; protein-bound adducts provide longer detection windows but lack the clinical standardization of cardiac troponin. ALDH2 activation remains preclinical for reperfusion microvascular injury. Prospective studies should further integrate genotype, enzyme activity, local carbonyl measurements, thromboinflammatory phenotyping, invasive physiology, and cardiac magnetic resonance endpoints.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058490","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":"Association of Cardiac Conduction System Radiation Doses with Incident Atrial Fibrillation in Lung Cancer.","authors":"Hakan Yalman, Ilayda Yalman, Mehmet Semih Belpinar, Murat Cimci, Halil Cumhur Yildirim, Fazilet Oner Dincbas, Kivanc Yalin","doi":"10.1007/s12012-026-10198-5","DOIUrl":"10.1007/s12012-026-10198-5","url":null,"abstract":"<p><p>Thoracic radiotherapy (RT) is linked to cardiovascular toxicity, but its impact on the cardiac conduction system, particularly the sinoatrial (SA) node, is poorly defined. We examined whether SA node radiation dose is associated with new-onset atrial fibrillation (AF), accounting for the competing risk of death. We retrospectively studied 84 lung cancer patients undergoing thoracic RT, stratified by maximum SA node dose (D_max) using an exploratory, data-derived threshold of 17.23 Gy. Cumulative incidence functions and Fine-Gray regression, treating death as a competing event, assessed AF risk. Median age was 68.5 years; median follow-up was 12.0 months. AF occurred in 9 patients (10.7%). The high-dose SA node group (>17.23 Gy) was significantly younger (65.5 vs. 70.0 years; P=0.010) with similar Mayo AF Risk Scores (P=0.821), yet had a higher 24-month cumulative incidence of AF (18.8% vs. 4.1%; Gray's test P=0.038). AV node D_max was not associated with AF but correlated with post-radiotherapy PR-interval prolongation (+14.1 ms; Spearman ρ=0.47, P=0.006). In an exploratory multivariable model adjusting for age, SA node D_max remained associated with AF (adjusted sHR 1.04 per 1-Gy; 95% CI 1.01-1.06; P=0.008), warranting cautious interpretation given the limited event number. In this hypothesis-generating, single-center cohort, higher SA node dose was associated with increased AF incidence independent of age, while AV node dose was linked to PR prolongation rather than AF. These preliminary findings require validation in larger, prospective, multicenter cohorts before the SA node can be considered a formal organ at risk in RT planning.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058502","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":"Association Between Blood Heavy Metals and Selenium with All-Cause Mortality in Cardiovascular-Kidney-Metabolic Syndrome Populations: Exploring the Mediating Effects of Inflammatory Biomarkers.","authors":"Hui Niu, Lin Zhang, Yikun Wang, Wenchang He, Rui Wang, Xinhong Li","doi":"10.1007/s12012-026-10179-8","DOIUrl":"10.1007/s12012-026-10179-8","url":null,"abstract":"<p><p>Cardiovascular-kidney-metabolic (CKM) syndrome, characterized by the pathophysiological interplay among metabolic disorders, chronic kidney disease (CKD), and cardiovascular disease (CVD), significantly elevates mortality risk. Environmental heavy metal exposure and selenium deficiency are implicated in these conditions, but their combined impact on CKM syndrome is unclear. To investigate the associations of blood heavy metals (lead [Pb], cadmium [Cd], mercury [Hg], manganese [Mn]) and selenium (Se) with all-cause mortality in CKM populations, and examine the mediating role of inflammatory biomarkers. This cross-sectional study with prospective mortality follow-up included 6,072 participants from NHANES (2011-2018). Kaplan-Meier curves, multivariable Cox regression models, and restricted cubic spline (RCS) analyses were employed to assess all-cause mortality associations. Subgroup and interaction analyses evaluated risks across demographic strata. Mediation analysis was employed to explore the mediating effects of inflammatory biomarkers (NLR, MLR, NMLR, and SIRI). The Weighted quantile sum (WQS) model was utilized to estimate the effects of combined blood metal exposures. Among 6,072 participants, 409 deaths occurred during follow-up. In the fully adjusted model, there was a significant negative correlation between blood selenium levels and all-cause mortality in the CKM population. Compared with the lowest quartile (Q1), the highest selenium quartile (Q4) was associated with a 38% reduced mortality risk (HR = 0.62, 95% CI: 0.45-0.85, P = 0.003). RCS analysis revealed an L-shaped dose-response relationship (P for nonlinear = 0.002). Subgroup analyses confirmed consistent associations in both non-advanced CKM (stages 0-2) and advanced CKM (stages 3-4) (all P < 0.05, P for interaction = 0.163). Mediation analysis revealed that NLR, MLR, NMLR, and SIRI partially mediated the association between blood selenium and all-cause mortality, and the mediated proportions were relatively modest (ranging from 3.57 to 5.29%). Higher blood selenium was associated with reduced all-cause mortality in CKM syndrome after adjustment for measured confounders, and mediation analysis suggested a potential partial role of inflammation in this association. These findings underscore the need for targeted interventions to mitigate mortality in this high-risk population.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015821","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":"The Interplay Between Thyroid Cancer and Cardiovascular Disease: Shared Mechanisms, Treatment Implications, and Survivorship Perspectives.","authors":"Leila Najd-Hassan-Bonab, Maryam Moazzam-Jazi, Raziyeh Abooshahab, Shabnam Heydarzadeh, Maryam S Daneshpour, Mehdi Hedayati","doi":"10.1007/s12012-026-10192-x","DOIUrl":"10.1007/s12012-026-10192-x","url":null,"abstract":"<p><p>The global incidence of thyroid cancer (TC), particularly differentiated thyroid cancer (DTC), has increased substantially over recent decades, while cardiovascular disease (CVD) remains the leading cause of death globally. As advances in diagnosis and treatment have significantly improved long-term survival in thyroid cancer patients, attention has increasingly shifted toward non-cancer complications, especially cardiovascular morbidity and mortality. Current evidence indicates that TC survivors have a higher risk of atrial fibrillation (AF), coronary artery disease (CAD), stroke, heart failure, and other cardiovascular complications than the general population. This association appears to result from a complex interaction between shared cardiometabolic risk factors and biological pathways. Obesity, metabolic syndrome, diabetes, hypertension, and dyslipidemia promote chronic inflammation, endothelial dysfunction, and insulin/IGF signaling, which contribute to atherosclerosis and tumor progression. Thyroid hormone dysregulation provides an additional link between thyroid cancer management and cardiovascular risk. Long-term thyroid-stimulating hormone (TSH) suppression therapy may induce subclinical hyperthyroidism and increase susceptibility to atrial fibrillation, ischemic heart disease, cardiac remodeling, and vascular dysfunction. Treatment-related factors, including thyroidectomy, radioactive iodine therapy, and targeted therapies, may also contribute to cardiovascular toxicity and influence long-term cardiovascular outcomes. Importantly, cardiovascular risk is heterogeneous among thyroid cancer survivors and may vary according to thyroid cancer risk category and current disease status, the intensity and duration of TSH suppression, radioactive iodine exposure, and patient-level characteristics such as age, sex, and baseline cardiovascular risk. This review synthesizes epidemiological and mechanistic evidence linking TC and CVD, with particular emphasis on shared metabolic and inflammatory pathways, hormonal and treatment-related factors, and changes in cardiovascular risk across different phases of thyroid cancer survivorship. Recognizing these determinants may support individualized cardiovascular risk assessment and help balance the oncologic benefits of thyroid cancer treatment against its potential long-term cardiovascular consequences.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015812","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":"The Potential Role of the Gut-Vascular Axis in Ciprofloxacin-Associated Aggravation of Aortic Dissection.","authors":"Hui Lv, Qi Wang, Asiya Abudesimu, Gulinazi Yesitayi, Aliya Aizitiaili, Dilixiati Siti, Xiang Ma","doi":"10.1007/s12012-026-10196-7","DOIUrl":"10.1007/s12012-026-10196-7","url":null,"abstract":"<p><p>Ciprofloxacin (CIP) is associated with an increased risk of aortic dissection (AD); however, the underlying mechanism remains unclear. This study investigates the potential contribution of gut microbiota and intestinal barrier alterations to CIP-associated AD progression. The AD model was established using a combination of β-aminopropionitrile and angiotensin II. The composition of the gut microbiota was analyzed using 16 S rRNA sequencing. In vivo experiments were conducted to investigate whether CIP aggravates AD through a potential gut-vascular axis involving intestinal alterations and increased circulating lipopolysaccharide (LPS) levels, which was further explored in human aortic smooth muscle cells (HASMCs). The results showed that CIP aggravated aortic injury and induced smooth muscle cell dysfunction in AD mice. CIP disrupted gut microbial composition and impaired intestinal barrier integrity, which was accompanied by increased circulating LPS levels. Additionally, in vitro experiments demonstrated that combined CIP and LPS stimulation enhanced HASMC apoptosis and phenotypic switching. Our findings suggest that CIP-associated intestinal alterations and elevated circulating LPS levels may contribute to AD progression through a potential gut-vascular axis, providing new insights into fluoroquinolone-associated vascular injury and potential gut-targeted interventions.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015729","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":"Genetic and Molecular Determinants of Cancer Therapy-Related Cardiovascular Toxicity.","authors":"Paulina Szubińska-Bałaban, Aneta Klotzka, Katarzyna Ziółkowska, Patrycja Marciniak-Stępak, Julia Niedzielska, Federico Russo, Amro Abu Suleiman, Filip Glista, Angelika Kuczmarska, Ewelina Bukowska-Olech","doi":"10.1007/s12012-026-10191-y","DOIUrl":"10.1007/s12012-026-10191-y","url":null,"abstract":"<p><p>Cancer therapy-related cardiovascular toxicity (CTR-CVT) is an umbrella term for myocardial, vascular, electrical, and inflammatory complications of cytotoxic, targeted, immune, and radiation-based therapies. Cancer therapy-related cardiac dysfunction (CTRCD) is used here more narrowly for treatment-related myocardial dysfunction, typically identified by changes in left ventricular ejection fraction, global longitudinal strain, and/or cardiac biomarkers. The pathophysiology of CTR-CVT is multifactorial, but the implicated pathways should not be interpreted as equally causal. The dominant initiating mechanism is therapy-specific - anthracycline injury is best supported by topoisomerase IIβ (TOP2B)-mediated DNA damage with secondary mitochondrial and redox injury; HER2-directed toxicity by disruption of NRG1-ERBB2/ERBB4 survival signalling; fluoropyrimidine toxicity by coronary vasomotor dysfunction; VEGF-pathway inhibition by endothelial dysfunction and hypertension; immune checkpoint inhibitor toxicity by loss of immune tolerance; and radiotherapy injury by endothelial and microvascular damage with progressive fibrosis. Mitochondrial dysfunction, oxidative stress, inflammation, calcium dysregulation, apoptosis, and ferroptosis frequently act as downstream or amplifying pathways, although the clinical relevance of several regulated cell-death mechanisms remains incompletely established. Genetic susceptibility may further modify risk, but the strength of evidence differs among reported loci. Replicated pharmacogenetic associations, rare variants in established cardiomyopathy genes, and preliminary candidate-gene findings should therefore be considered separately. Most available studies remain limited by small cohorts, heterogeneous phenotyping, ancestry imbalance, and incomplete external replication. This review critically evaluates the hierarchy and strength of mechanistic and genetic evidence and discusses the extent to which these findings can currently inform risk stratification, surveillance, prevention, and treatment in precision cardio-oncology.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":"26 10","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012125","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}