Cardiovascular Toxicology最新文献

{"title":"SUZ12-Increased NRF2 Alleviates Cardiac Ischemia/Reperfusion Injury by Regulating Apoptosis, Inflammation, and Ferroptosis.","authors":"Guoyong Zhang, Zhimin Ma, Zheng Ma, Peilin Liu, Lin Zhang, Zheng Lian, Caixia Guo","doi":"10.1007/s12012-024-09950-6","DOIUrl":"10.1007/s12012-024-09950-6","url":null,"abstract":"<p><p>Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-sensitive transcriptional factor that enables cells to resist oxidant responses, ferroptosis and inflammation. Here, we set out to probe the effects of NRF2 on cardiomyocyte injury under acute myocardial infarction (AMI) condition and its potential mechanism. Human cardiomyocytes were exposed to hypoxia/reoxygenation (H/R) to induce cell injury. qRT-PCR and western blot assays were used to detect the levels of mRNAs and proteins. Cardiomyocyte injury was determined by detecting the levels of lactate dehydrogenase and creatine Kinase MB (CK-MB). Cell apoptosis was investigated by flow cytometry and related markers. Levels of IL-6, IL-10, and TNF-α were measured by ELISA. Cell ferroptosis was assessed by detecting the production of reactive oxygen species (ROS), malonaldehyde (MDA), reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio, Fe + content, and related regulators. The interaction between NRF2 and the suppressor of zest 12 (SUZ12) was analyzed by using dual-luciferase reporter and RNA immunoprecipitation assays. AMI rat models were established for in vivo analysis. NRF2 was lowly expressed in AMI patients and H/R-induced cardiomyocytes. Forced expression of NRF2 reduced H/R-induced cardiomyocyte injury, apoptosis, inflammation, and ferroptosis. Moreover, NRF2 overexpression improved cardiac function and injury in vivo. Mechanistically, SUZ12 bound to the promoter of NRF2 and promoted its expression. Further functional analyses showed that SUZ12 overexpression reduced H/R-induced cardiomyocyte injury, apoptosis, inflammation, and ferroptosis, which were reversed by NRF2 silencing. SUZ12-increased NRF2 suppressed H/R-induced cardiomyocyte injury, apoptosis, inflammation, and ferroptosis in vitro and improved cardiac functions in rats with I/R injury, suggesting the potential cardioprotective effect of NRF2 in cardiac injury during AMI.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"97-109"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892272","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":"Diagnostic Utility of Combining Homocysteine, Lipoprotein-Associated Phospholipase A2, and the C-Reactive Protein-to-Albumin Ratio for Assessing Carotid Atherosclerosis and Plaque Stability in Patients with Essential Hypertension.","authors":"Minjie Yuan, Linjuan Feng, Dongqi Zhao, Dongdong Shi, Hui Wang, Junbo Wei, Man Wang","doi":"10.1007/s12012-024-09939-1","DOIUrl":"10.1007/s12012-024-09939-1","url":null,"abstract":"<p><p>The objective of this study is to determine the diagnostic utility of combining homocysteine (HCY), lipoprotein-associated phospholipase A2 (LP-PLA2), and the C-reactive protein-to-albumin ratio (CAR) for carotid atherosclerosis (CAS) and plaque stability in patients with essential hypertension (EH). A total of 280 patients with EH were divided into 2 groups according to ultrasound diagnosis: CAS (n = 106) and non-CAS (N-CAS [n = 174]). The CAS group was further segmented into plaque-stable (n = 50) and plaque non-stable (n = 56) groups. General data were collected for all patients. Risk factors associated with CAS and plaque instability in patients with EH, and the diagnostic utility of HCY, LP-PLA2, and CAR testing alone, or in combination, for assessing CAS and plaque instability were determined. Mean age, systolic blood pressure (SBP), duration of EH, smoking, total cholesterol high-density lipoprotein cholesterol, HCY, LP-PLA2 levels, and CAR were higher in the CAS group than those in the N-CAS group (P < 0.05). SBP, duration of EH, HCY and LP-PLA2 levels, and CAR were independent risk factors for CAS (P < 0.05). In addition, HCY, LP-PLA2, and CAR alone demonstrated significant diagnostic efficacy (P < 0.001) but were inferior to the combined diagnostic utility of the 3 parameters (P < 0.001). HCY and LP-PLA2 levels, and CAR were higher in the plaque non-stable than in the plaque-stable group (P < 0.05). Duration of EH, low-density lipoprotein cholesterol, HCY, LP-PLA2, and CAR independently influenced plaque instability in patients with CAS (P < 0.05). The combined diagnostic utility of HCY, LP-PLA2, and CAR (P < 0.001) was superior to that of each parameter alone and demonstrated more pronounced diagnostic efficacy (P < 0.001). HCY, LP-PLA2, and CAR were independent risk factors for CAS and plaque instability in patients with EH. HCY, LP-PLA2, and CAR demonstrated significant diagnostic efficacy for CAS and plaque instability, and combination of the 3 demonstrated the most pronounced diagnostic efficacy.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"24-33"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615312","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":"Ultrasound-Targeted β-Catenin Gene Therapy Improves the Cardiac Function in Mice After Myocardial Infarction.","authors":"Lei Yang, Tong Gao, Yu Huang, Pei-He Wang, Xin-Hao Han, Jie Wu, Lei Huang, Qing-En Da, Kun-Fu Ouyang, Zhen Han, Hai Tian, Lu Sun","doi":"10.1007/s12012-024-09946-2","DOIUrl":"10.1007/s12012-024-09946-2","url":null,"abstract":"<p><p>Gene therapy has received great attention as a therapeutic approach to improve cardiac function post-myocardial infarction (MI), but its limitation lies in the lack of targeting. This study explored the use of ultrasound-targeted microbubble destruction (UTMD) technique to deliver β-catenin gene to the myocardium, aiming to evaluate its efficacy in preventing cardiac dysfunction post-MI. A cationic microbubble solution containing β-catenin gene pcDNA3.1 plasmid was injected through the tail vein at a rate of 0.6 mL/h, and ultrasound beams were delivered to the heart using GE Vivid 7 Medical Ultrasound System M3s Transducer. Bioluminescence imaging was used to analyze the efficiency of UTMD gene transfection into the myocardium. β-catenin levels were detected by real-time polymerase chain reaction and western blot. Additionally, MI was induced in mice by surgical ligation of the left coronary artery, and cardiac function was evaluated using echocardiography at 14 and 28 days post-surgery. Masson's trichrome staining was employed to determine infarct size. Blood vessel density was also measured. TUNEL assay was used to measure cardiomyocyte apoptosis. Furthermore, mouse cardiac stem cells were isolated using flow cytometry, and Giemsa stain was applied to evaluate the colony adhesion. UTMD delivered the gene to the heart with high efficiency and specificity in vivo. The β-catenin expression was significantly increased in the myocardium (P < 0.01). After MI, the β-catenin group exhibited a notable improvement in the gene therapy-induced neovascularization in the border zone (P < 0.01) and the number and function of cardiac stem cells (P < 0.01), and a significant decrease in cardiomyocyte apoptosis in the heart tissue (P < 0.01). β-catenin gene pre-treated with UTMD can reduce the impact of myocardial injury and promote cardiac self-repair after MI.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"74-84"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799444","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":"Inhibition of CB1R in the Hypothalamic Paraventricular Nucleus Ameliorates Hypertension Through Wnt/β-Catenin/RAS Pathway.","authors":"Hong-Li Gao, Yu Yang, Hua Tian, Li-Yan Fu, Kai-Li Liu, Xiu-Yue Jia, Xiao-Lian Shi, Yu-Ming Kang, Xiao-Jing Yu","doi":"10.1007/s12012-024-09938-2","DOIUrl":"10.1007/s12012-024-09938-2","url":null,"abstract":"<p><p>The hypothalamic paraventricular nucleus (PVN), as an important integrating center, plays a prominent role in the pathogenesis of hypertension, in maintaining the stability of cardiovascular activity through peripheral sympathetic nervous activity and secretion of various humoral factors. Acknowledging that the mechanistic targets of the endocannabinoid type 1 receptor (CB1R) are the key signaling systems involved in the regulation of hypertension, we sought to clarify whether inhibition of CB1R within the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats were randomly assigned to different groups and treated with bilateral PVN injections of AM251 (CB1R antagonist, 10 µg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for four weeks. Bilateral PVN injections of AM251 significantly decreased the heart rate, the body weight and the mean arterial pressure in SHRs. AM251 lowered the expression of CB1R, Wnt3, active-β-catenin, p-IKKβ, RAS components, pro-inflammatory cytokines and elevated the expression level of Glycogen synthase kinase3β and Superoxide Dismutase in the PVN of hypertensive rats. Our findings suggest that inhibition of CB1R in the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway and broaden our current understanding of the pathological mechanism and clinical treatment of hypertension.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"9-23"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521093","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 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}