Cardiovascular Toxicology最新文献

{"title":"Association Between Serum Essential Metal Elements and Blood Pressure in Children: A Cohort Study.","authors":"Muhammad Fahad Tahir, Xiaofei Wu, Yuwei Wang, Qin Liu, Xizhou An, Daochao Huang, Lijing Chen, Lanling Chen, Xiaohua Liang","doi":"10.1007/s12012-024-09948-0","DOIUrl":"10.1007/s12012-024-09948-0","url":null,"abstract":"<p><p>A limited number of cohort studies have explored the impact of serum essential metal elements on blood pressure (BP) or glycolipids and their regulatory mechanism in children. This study aimed to investigate the relationship between serum metal concentrations of iron (Fe), zinc (Zn), calcium (Ca), copper (Cu), and magnesium (Mg) and BP in children, and explore the potential mediating effects of glycolipid profiles. This cohort study included 1993 children (3566 BP measurements) aged 6-14 years in Chongqing, China. Serum essential metals, BP, lipid profiles, and glucose and insulin levels were measured. The relationship between serum metal levels and BP was analyzed using generalized linear and regression models, and a mediation analysis was performed to examine the potential mediating role of glycolipids. After adjusting for confounders, positive associations were found between serum Fe and Zn levels and BP parameters (all P < 0.05). A \"U\" style relationship between Cu and BP was found. Stronger associations were found in children aged ≤ 10 years, with sex-specific differences for Fe, Zn, and Cu. The relationship between elevated BP and serum Mg and Ca was not found. Our study found that triglycerides showed a significant relationship with Fe and Zn levels (P < 0.005). Moreover, triglycerides, partially mediate the effects of Zn on elevated BP. Serum Fe, Zn, and Cu concentrations were associated with BP in children, and age and sex differences were observed. Triglycerides may play a mediating role. These findings highlight the importance of maintaining an optimal serum essential metal status for cardiovascular health in children and suggest potential early prevention strategies.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"121-134"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846145","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":"Isoprenaline Inhibits Histone Demethylase LSD1 to Induce Cardiac Hypertrophy.","authors":"Lili Wu, Bo Yang, Yingze Sun, Guanwei Fan, Lina Ma, Ying Ma, Xianjia Xiong, Hui Zhou, Huiping Wang, Ling Zhang, Bing Yang","doi":"10.1007/s12012-024-09937-3","DOIUrl":"10.1007/s12012-024-09937-3","url":null,"abstract":"<p><p>Histone demethylation in cardiac hypertrophy is poorly understood. This study aims to determine the role of the histone demethylase LSD1 in pathological cardiac hypertrophy. Both isoprenaline (ISO)-treated and transverse aortic constriction (TAC)-treated rats developed hypertrophic hearts. LSD1 was significantly decreased; the histone marks mono- and dimethyl H3K4 and H3K9 (H3K4me1/2 and H3K9me1/2) were significantly up-regulated in the hypertrophic heart tissue, as well as the expression of the ANP, α-HMC and MLV-2v genes. An LSD1 inhibitor, OG-L002 could also induce cardiac hypertrophy and enhance the induction of cardiac hypertrophy by ISO. Overexpressed LSD1 abolished ISO-induced cardiac hypertrophy and downregulated H3K4me1/2 and H3K9me1/2 expression. Overexpression of LSD1 also reduced the expression of ANP, α-HMC and MLV-2v. In addition, we have reported isoprenaline (ISO) as one of the histone demethylase LSD1 inhibitors. This was confirmed by molecular docking, molecular dynamic studies and a histone demethylation assay. The H3K4me1/2 expression increases with the incubation of ISO in HEK 293T and HELA cells. CaMKII could be significantly activated by the LSD1 inhibitor OG-L002 as well as by ISO in rats. In summary, we have identified a novel role for LSD1 in initiating and maintaining cardiac hypertrophy.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"34-47"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615325","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":"Dapagliflozin Suppresses High Glucose-Induced Proliferation, Oxidative Stress, and Fibrosis by Reducing Mettl3-Induced m6A Modification in Marcks mRNA.","authors":"Binhao Shi, Jianfei Wang, Jing Zhang, Ji Li, Yancheng Hao, Xianhe Lin, Ren Zhao","doi":"10.1007/s12012-024-09945-3","DOIUrl":"10.1007/s12012-024-09945-3","url":null,"abstract":"<p><p>Diabetic cardiomyopathy (DCM) is a common and severe complication of Diabetes mellitus (DM). Dapagliflozin (DAPA) is an oral anti-diabetic drug worldwide for the treatment of type 2 DM. However, the action and mechanism of DAPA in cardiac fibrosis during DCM remain vague. Primary cardiac fibroblasts (CFs) were incubated with high glucose (HG) in vitro. Cell proliferation was detected by MTT and EdU assays. Oxidative stress was evaluated by determining the production of reactive oxygen species and malondialdehyde. Cell fibrosis was assessed by detecting fibrosis-related proteins by western blotting. Levels of Mettl3 (Methyltransferase 3) and Marcks (myristoylated alanine-rich C kinase substrate) were measured using qRT-PCR and western blotting. The m6A modification profile was determined by methylated RNA immunoprecipitation assay and the interaction between Mettl3 and Marcks was verified using dual-luciferase reporter and RIP assays. DAPA treatment alleviated HG-induced proliferation, oxidative stress, and fibrosis in CFs. HG promoted the expression of Mettl3 in CFs. Knockdown of Mettl3 reversed HG-induced proliferation, oxidative stress, and fibrosis in CFs; moreover, forced expression of Mettl3 abolished the protective effects of DAPA on CFs under HG condition. Mechanistically, Mettl3 interacted with Marcks in CFs and induced Marcks mRNA m6A modification. HG induced high expression of Marcks in CFs. The overexpression of Marcks could counteract DAPA or Mettl3 knockdown-evoked inhibitory effects on CF proliferation, oxidative stress, and fibrosis under HG condition. Dapagliflozin suppressed HG-induced proliferation, oxidative stress, and fibrosis by reducing Mettl3-induced m6A modification in Marcks mRNA.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"110-120"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666972","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":"Di-(2-ethylhexyl) Phthalate Exposure Induces Developmental Toxicity in the Mouse Fetal Heart via Mitochondrial Dysfunction.","authors":"Yafei Guo, Bowen Li, Yu Yan, Nanjun Zhang, Shuran Shao, Lixia Yang, Lixue Ouyang, Ping Wu, Fan Ma, Hongyu Duan, Kaiyu Zhou, Yimin Hua, Chuan Wang","doi":"10.1007/s12012-024-09936-4","DOIUrl":"10.1007/s12012-024-09936-4","url":null,"abstract":"<p><p>Congenital heart disease (CHD) is a major cause of infant mortality and morbidity, with growing interest in the role of environmental factors in its etiology. Di-(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has been implicated in the development of CHD. This study aimed to investigate the effects of DEHP exposure on fetal heart development in mice. Pregnant mice exposed to DEHP exhibited increased fetal malformations, decreased fetal weight, and reduced crown-rump length.f Transcriptomic analysis revealed the downregulation of genes involved in aerobic respiration and mitochondrial ATP synthesis. Functional assays demonstrated reduced mitochondrial respiration, decreased ATP production, elevated reactive oxygen species levels, and lowered mitochondrial membrane potential in DEHP-exposed fetal cardiomyocytes. These findings underscore the detrimental effects of DEHP on fetal cardiac health and provide insights into the molecular mechanisms underlying DEHP-induced CHD. Understanding these mechanisms is crucial for developing preventive strategies against environmental toxicants that affect fetal cardiac development.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"48-57"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495720","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":"Exposure to Pyriproxyfen Impacts Heart Development Causing Tissue and Cellular Impairments, Heart Arrhythmia and Reduced Embryonic Growth.","authors":"Maria Fernanda Conte Bernhardt, Nathália Ronconi-Krüger, Evelise Maria Nazari","doi":"10.1007/s12012-024-09944-4","DOIUrl":"10.1007/s12012-024-09944-4","url":null,"abstract":"<p><p>In recent years, concerns have been raised regarding the safety of exposure to pyriproxyfen (PPF), a larvicide commonly used in drinking water reservoirs to control populations of disease-vector mosquitoes for human safety. These concerns are focused mainly on exposure by pregnant women, since studies have shown deleterious effects of PPF on embryonic development, mainly addressing the central nervous system. However, since previous studies showed reduced growth in embryos exposed to PPF, we hypothesize that PPF exposure impairs the cardiovascular system, responsible for ensuring appropriate blood supply, which leads to stunted growth. This study aimed to investigate the impact of PPF exposure on heart ventricular morphology, its influence on cell proliferation and apoptosis, as well as assess the impact on the functionality of the heart and on embryonic growth. Chicken embryos were used as a model and two sublethal concentrations were tested: 0.01 mg/L and 10 mg/L PPF. Thinning of cardiac tissue was evident in heart structures at 10 mg/L PPF. Furthermore, DNA double-strand breaks and reduced cell proliferation were observed, combined with decreased apoptosis suggesting cell cycle arrest, especially in the left ventricle for both concentrations. In addition, these PPF concentrations induced heart arrhythmia, although no changes in heart rate were observed. Embryos exposed to 0.01 mg/L showed reduced body and heart mass, crown-rump length, and thoracic perimeter, while head circumference was reduced in both exposed groups. Together, combining morphological, molecular, and physiological parameters, this study showed the cardiotoxic effects of PPF exposure and elucidated its impacts on embryonic growth.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"85-96"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615330","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":"Proteomics Reveals Divergent Cardiac Inflammatory and Metabolic Responses After Inhalation of Ambient Particulate Matter With or Without Ozone.","authors":"Yue Ge, Maliha S Nash, Witold M Winnik, Maribel Bruno, William T Padgett, Rachel D Grindstaff, Mehdi S Hazari, Aimen K Farraj","doi":"10.1007/s12012-024-09931-9","DOIUrl":"10.1007/s12012-024-09931-9","url":null,"abstract":"<p><p>Inhalation of ambient particulate matter (PM) and ozone (O₃) has been associated with increased cardiovascular morbidity and mortality. However, the interactive effects of PM and O₃ on cardiac dysfunction and disease have not been thoroughly examined, especially at a proteomic level. The purpose of this study was to identify and compare proteome changes in spontaneously hypertensive (SH) rats co-exposed to concentrated ambient particulates (CAPs) and O₃, with a focus on investigating inflammatory and metabolic pathways, which are the two major ones implicated in the pathophysiology of cardiac dysfunction. For this, we measured and compared changes in expression status of 9 critical pro- and anti-inflammatory cytokines using multiplexed ELISA and 450 metabolic proteins involved in ATP production, oxidative phosphorylation, cytoskeletal organization, and stress response using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) in cardiac tissue of SH rats exposed to CAPs alone, O₃ alone, and CAPs + O₃. Proteomic expression profiling revealed that CAPs alone, O₃ alone, and CAPs + O₃ differentially altered protein expression patterns, and utilized divergent mechanisms to affect inflammatory and metabolic pathways and responses. Ingenuity Pathway Analysis (IPA) of the proteomic data demonstrated that the metabolic protein network centered by gap junction alpha-1 protein (GJA 1) was interconnected with the inflammatory cytokine network centered by nuclear factor kappa beta (NF-kB) potentially suggesting inflammation-induced alterations in metabolic pathways, or vice versa, collectively contributing to the development of cardiac dysfunction in response to CAPs and O₃ exposure. These findings may enhance understanding of the pathophysiology of cardiac dysfunction induced by air pollution and provide testable hypotheses regarding mechanisms of action.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1348-1363"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458727","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 Multifaceted Roles of Hippo-YAP in Cardiovascular Diseases.","authors":"Hao Wu, Yan-Nan Che, Qi Lan, Yi-Xiang He, Ping Liu, Ming-Tai Chen, Li Dong, Meng-Nan Liu","doi":"10.1007/s12012-024-09926-6","DOIUrl":"10.1007/s12012-024-09926-6","url":null,"abstract":"<p><p>The Hippo-yes-associated protein (YAP) signaling pathway plays a crucial role in cell proliferation, differentiation, and death. It is known to have impact on the progression and development of cardiovascular diseases (CVDs) as well as in the regeneration of cardiomyocytes (CMs). However, further research is needed to understand the molecular mechanisms by which the Hippo-YAP pathway affects the pathological processes of CVDs in order to evaluate its potential clinical applications. In this review, we have summarized the recent findings on the role of the Hippo-YAP pathway in CVDs such as myocardial infarction, heart failure, and cardiomyopathy, as well as its in CM development. This review calls attention to the potential roles of the Hippo-YAP pathway as a relevant target for the future treatment of CVDs.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1410-1427"},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371053","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":"Unveiling the Mechanism of Protective Effects of Tanshinone as a New Fighter Against Cardiovascular Diseases: A Systematic Review.","authors":"Mohammad Mahdi Dabbaghi, Hesan Soleimani Roudi, Rozhan Safaei, Vafa Baradaran Rahimi, Mohammad Reza Fadaei, Vahid Reza Askari","doi":"10.1007/s12012-024-09921-x","DOIUrl":"10.1007/s12012-024-09921-x","url":null,"abstract":"<p><p>Tanshinone, a natural compound found in the roots of Salvia miltiorrhiza, has been shown to possess various pharmacological properties, including anti-inflammatory, antioxidant, and cardiovascular protective effects. This article aims to review the literature on the cardiovascular protective effects of tanshinone and its underlying mechanisms. Tanshinone has been demonstrated to improve cardiac function, reduce oxidative stress, and inhibit inflammation in various animal models of cardiovascular diseases. Additionally, it has been shown to regulate multiple signaling pathways involved in the pathogenesis of cardiovascular diseases, such as the PI₃K/AKT, MAPK, and NF-κB pathways. Clinical studies have also suggested that tanshinone may have therapeutic potential for treating cardiovascular diseases. In conclusion, tanshinone has emerged as a promising natural compound with significant cardiovascular protective effects, and further research is warranted to explore its potential clinical applications.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1467-1509"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280634","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":"Extracellular Volume and Fibrosis Volume of Left Ventricular Myocardium Assessed by Cardiac Magnetic Resonance in Vaccinated and Unvaccinated Patients with a History of SARS-CoV-2 Infection.","authors":"Paweł Gać, Wojciech Hajdusianek, Aleksandra Żórawik, Małgorzata Poręba, Rafał Poręba","doi":"10.1007/s12012-024-09929-3","DOIUrl":"10.1007/s12012-024-09929-3","url":null,"abstract":"<p><p>Cardiac magnetic resonance (CMR) enables the assessment of tissue characteristics of the myocardium. Changes in the extracellular volume (ECV) and fibrosis volume (FV) of the myocardium are sensitive and early pathogenetic markers and have prognostic significance. The aim of the study was to assess ECV and FV of left ventricular myocardium in T1 mapping sequence in patients with a history of SARS-CoV-2 infection, considering vaccination status against COVID-19. The study group consisted of 97 patients (52.54 ± 8.31 years, 53% women and 47% men). The participants were divided into three subgroups: A) patients with a history of symptomatic SARS-CoV-2 infection, unvaccinated against COVID-19 (n = 39), B) patients with a history of symptomatic SARS-CoV-2 infection, with a full vaccination schedule against COVID-19 (n = 22), and C) persons without a history of SARS-CoV-2 infection constituting the control subgroup (C, n = 36). All patients underwent 1.5 T cardiac magnetic resonance. In subgroup A compared to subgroups B and C, both the ECV whole myocardium and ECV segments 2, 5-6, 8, and 10-11 were statistically significantly higher. In addition, the ECV segment 16 was statistically significantly higher in subgroup A than in subgroup C. Also, the FV whole myocardium was statistically significantly higher in subgroup A in comparison to subgroups B and C. There were no significant differences in ECV and FV between subgroups B and C. In summary, unvaccinated against COVID-19 patients with a history of symptomatic SARS-CoV-2 infection have higher myocardial ECV and FV values in the T1 mapping sequence, compared to those without COVID-19 and those suffering from COVID-19, previously vaccinated with the full vaccination schedule.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1455-1466"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458724","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":"Advances in Factors Affecting ALDH2 Activity and its Mechanisms.","authors":"Yun Liu, Xuemei Liu, Chang Pan","doi":"10.1007/s12012-024-09923-9","DOIUrl":"10.1007/s12012-024-09923-9","url":null,"abstract":"<p><p>Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme primarily involved in the detoxification of alcohol-derived aldehyde and endogenous toxic aldehydes. It exhibits widespread expression across various organs and exerts a broad and significant impact on diverse acute cardiovascular diseases, including acute coronary syndrome, acute aortic dissection, hypoxic pulmonary hypertension, and heart failure. The ALDH2 rs671 variant represents the most prevalent genetic variant in East Asian populations, with carriage rates ranging from 30 to 50% among the Chinese population. Given its widespread presence in the body, the wide range of diseases it affects, and its high rate of variation, it can serve as a crucial tool for the precise prevention and treatment of acute cardiovascular diseases, while offering individualized medication guidance. This review aims to provide a comprehensive overview of the latest advancements in factors affecting ALDH2 activity, encompassing post-transcriptional modifications, modulators of ALDH2, and relevant clinical drugs.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1428-1438"},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371052","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}