Cardiovascular Toxicology最新文献

{"title":"Novel Insights into Causal Effects of Serum Lipids and Apolipoproteins on Cardiovascular Morpho-Functional Phenotypes.","authors":"Ankang Liu, Xiaohong Liu, Yuanhao Wei, Xiqiao Xiang, Yi Chen, Ziwei Zheng, Changde Xu, Shaoling Yang, Kun Zhao","doi":"10.1007/s12012-024-09930-w","DOIUrl":"10.1007/s12012-024-09930-w","url":null,"abstract":"<p><p>Previous observational studies have explored the association between serum lipids, apolipoproteins, and adverse ventricular/aortic structure and function. However, whether a causal link exists is uncertain. This study employed a two-sample Mendelian randomization (MR), colocalization, reverse, and multivariable MR (MVMR) approach to examine the causal associations among five serum lipids, two apolipoproteins, and 32 cardiac magnetic resonance (CMR) traits. Utilizing single-nucleotide polymorphisms (SNPs) linked to serum lipids and apolipoproteins as instrumental variables. CMR traits from seven independent genome-wide association studies served as preclinical endophenotypes, offering insights into aortic and cardiac structure/function. The primary analysis utilized a random-effects inverse variance method (IVW), followed by sensitivity and validation analyses. In the primary IVW MR analyses, genetically predicted low-density lipoprotein cholesterol (LDL-C) levels were positively correlated with increased descending aorta strain (DAo strain) (β = 0.098; P = 2.69E-07) and ascending aorta strain (AAo strain) (β = 0.079; P = 5.19E-05). Genetically predicted high-density lipoprotein cholesterol (HDL-C) levels were positively correlated with left ventricular radial peak diastolic strain rate (LV-PDSRll) (β = 0.176; P = 2.89E-05) and the left ventricular longitudinal peak diastolic strain rate (LV-PDSRrr) (β = 0.059; P = 2.44E-06), and negatively correlated with left ventricular regional wall thickness (LVRWT). While apolipoprotein B (ApoB) levels were positively correlated with AAo strain (β = 0.076; P = 1.16E-05), DAo strain (β = 0.065; P = 2.77E-05). A shared causal variant was identified to demonstrate the associations of ApoB with AAo strain and DAo strain using colocalization analysis. Sensitivity analyses confirmed the robustness of these associations. Targeting lipid and apolipoprotein levels through interventions may provide novel strategies for the primary prevention of CVDs.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1364-1379"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406161","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":"Tanshinone IIA Exerts Cardioprotective Effects Through Improving Gut-Brain Axis Post-Myocardial Infarction.","authors":"Tong Zhu, Jie Chen, Mingxia Zhang, Zheng Tang, Jie Tong, Xiuli Hao, Hongbao Li, Jin Xu, Jinbao Yang","doi":"10.1007/s12012-024-09928-4","DOIUrl":"10.1007/s12012-024-09928-4","url":null,"abstract":"<p><p>Myocardial infarction (MI) is a lethal cardiovascular disease worldwide. Emerging evidence has revealed the critical role of gut dysbiosis and impaired gut-brain axis in the pathological progression of MI. Tanshinone IIA (Tan IIA), a traditional Chinese medicine, has been demonstrated to exert therapeutic effects for MI. However, the effects of Tan IIA on gut-brain communication and its potential mechanisms post-MI are still unclear. In this study, we initially found that Tan IIA significantly reduced myocardial inflammation, apoptosis and fibrosis, therefore alleviating hypertrophy and improving cardiac function following MI, suggesting the cardioprotective effect of Tan IIA against MI. Additionally, we observed that Tan IIA improved the gut microbiota as evidenced by changing the α-diversity and β-diversity, and reduced histopathological impairments by decreasing inflammation and permeability in the intestinal tissues, indicating the substantial improvement of Tan IIA in gut function post-MI. Lastly, Tan IIA notably reduced lipopolysaccharides (LPS) level in serum, inflammation responses in paraventricular nucleus (PVN) and sympathetic hyperexcitability following MI, suggesting that restoration of Tan IIA on MI-induced brain alterations. Collectively, these results indicated that the cardioprotective effects of Tan IIA against MI might be associated with improvement in gut-brain axis, and LPS might be the critical factor linking gut and brain. Mechanically, Tan IIA-induced decreased intestinal damage reduced LPS release into serum, and reduced serum LPS contributes to decreased neuroinflammation with PVN and sympathetic inactivation, therefore protecting the myocardium against MI-induced injury.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1317-1334"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388253","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":"Protective Effect of Berberine Nanoparticles Against Cardiotoxic Effects of Arsenic Trioxide.","authors":"Seyed Hadi Hosseini, Maryam Nazarian, Shahnaz Rajabi, Amir Masoud Jafari-Nozad, Behzad Mesbahzadeh, Saeed Samargahndian, Tahereh Farkhondeh","doi":"10.1007/s12012-024-09927-5","DOIUrl":"10.1007/s12012-024-09927-5","url":null,"abstract":"<p><p>Arsenic trioxide (ATO) is a potent and highly effective chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, the clinical use of ATO is hampered by different cardiopathologic outcomes, such as arrhythmia and heart failure. Berberine has several beneficial effects because of its antioxidant activity; however, the potential cardioprotective function of this alkaloid against arsenic-induced cardiac toxicity has not been fully investigated. In this study, we evaluated the effect of ATO in rat heart tissue and the effect of berberine nanoparticles (NB) on cardiac enzyme levels, oxidative stress (OS) indices, and histopathological changes in heart tissue. Thirty Wistar rats were randomly allocated into five groups (n = 6): (1) Control animals that received 0.5 cc saline via gavage, (2) ATO group (4 mg/kg), (3) ATO + NB (2.5 mg/kg), (4) ATO + NB (5 mg/kg), and (5) ATO + NB (10 mg/kg) groups. Treatments were administered intraperitoneally for 45 days. Cardiac enzymes and OS biomarkers in heart tissue were measured. Histopathological examination of the heart tissue was also conducted at the end of the study. ATO injection significantly increased cardiac enzyme levels and OS biomarkers in rat's heart tissue. It also changed the histological features of the heart. NB administration significantly decreased the serum and tissue levels of cardiac enzyme and OS biomarkers in ATO-exposed animals (p < 0.05) and improved myocardial structural damage. NB, potent antioxidant, can reduce the unfavorable effects of ATO in rat heart tissue by balancing OS markers.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1311-1316"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342239","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":"LncRNA MALAT1 to Enhance Pyroptosis in Viral Myocarditis Through UPF1-Mediated SIRT6 mRNA Decay and Wnt-β-Catenin Signal Pathway.","authors":"Min Zeng, Zhi Chen, Yefeng Wang, Zhou Yang, Jinxing Xiang, Xiang Wang, Xun Wang","doi":"10.1007/s12012-024-09922-w","DOIUrl":"10.1007/s12012-024-09922-w","url":null,"abstract":"<p><p>Viral myocarditis (VMC) is an inflammatory disease of the myocardium caused by cardioviral infection, especially coxsackievirus B3 (CVB3), and is a major contributor to acute heart failure and sudden cardiac death in children and adolescents. LncRNA MALAT1 knockdown reportedly inhibits the differentiation of Th17 cells to attenuate CVB3-induced VMC in mice. Moreover, long non-coding RNAs (lncRNAs) interact with RNA-binding proteins (RBPs) to regulate UPF1-mediated mRNA decay. However, it remains unclear whether MALAT1 can bind to UPF1 to mediate the mRNA decay of its target genes in VMC. Herein, we aimed to explore the effect of lncRNA MALAT1 on UPF1-mediated SIRT6 mRNA decay in VMC using in vivo and in vitro experiments. CVB3-infected BABL/C mice were used as VMC models, and MALAT1 interfering adenovirus was injected to achieve MALAT1 knockdown. The heart function of the VMC mice was assessed using echocardiography. Pathological changes in myocardial tissues were assessed after hematoxylin-eosin staining. Myocardial injury and inflammation were evaluated by measuring creatine kinase isoenzyme B, cardiac troponin T, interleukin (IL)-1β, and IL-18. TUNEL staining was performed to assess apoptosis in myocardial tissues. In vitro experiments were performed using H9c2 cells after transfection and CVB3 infection. The lactic dehydrogenase release, caspase-1 activity, and IL-1β and IL-18 levels in the cellular supernatant were detected. Western blotting was performed to determine the expression of pyroptosis-related proteins (GSDMD-N, NLRP3, ASC, and Cleaved-Caspase-1) and Wnt/β-catenin signal pathway-related proteins (Wnt1, β-catenin, and p-GSK-3β). RNA immunoprecipitation and RNA stability assays assessed the relationship between MALAT1, UPF1, and SIRT6. CVB3-infected mice and H9c2 cells exhibited elevated MALAT1 and reduced SIRT6 expression. MALAT1 knockdown or SIRT6 overexpression suppressed inflammation and pyroptosis and inhibited the activation of the Wnt/β-catenin signal pathway in myocardial tissues and cells. MALAT1 enhanced the enrichment of SIRT6 mRNA by UPF1 and disturbed the stability of SIRT6 mRNA to promote the development of VMC. MALAT1 can bind UPF1 to mediate SIRT6 mRNA decay and activate the Wnt/β-catenin signal pathway in VMC.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1439-1454"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375133","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":"Potential Player of Platelet in the Pathogenesis of Cardiotoxicity: Molecular Insight and Future Perspective.","authors":"Arash Amin, Ahmad Mohajerian, Sara Rashki Ghalehnoo, Mehdi Mohamadinia, Shana Ahadi, Tooba Sohbatzadeh, Mahboubeh Pazoki, Afshin Hasanvand, Ferdos Faghihkhorasani, Zeinab Habibi","doi":"10.1007/s12012-024-09924-8","DOIUrl":"10.1007/s12012-024-09924-8","url":null,"abstract":"<p><p>Cancer patients may encounter the onset of cardiovascular disease due to tumor advancement or chemotherapy, commonly known as \"cardiotoxicity.\" In this respect, the conventional chemotherapy treatment protocol involves a mixture of different medications. These medications can be detrimental to cardiac tissue, consequently exposing the patient to the possibility of irreversible cardiac injury. The enhancement of oxidative stress and inflammation is an important mechanism of chemotherapeutic agents for developing cardiotoxicity. Regarding their dual pro- and anti-inflammatory functions, platelets can significantly influence the progression or suppression of cardiotoxicity. Therefore, the expression of platelet activatory markers can serve as valuable prognostic indicators for cardiotoxicity. The primary objective of this study is to examine the significance of platelets in cardiotoxicity and explore potential strategies that could effectively target malignant cells while minimizing their cytotoxic impact, such as cardiotoxicity and thrombosis.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1381-1394"},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458725","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":"Environmental Heavy Metal Exposure and Associated Cardiovascular Diseases in Light of the Triglyceride Glucose Index.","authors":"Muhammad Bilal Sardar, Mohsin Raza, Ammara Fayyaz, Muhammad Asfandyar Nadir, Zain Ali Nadeem, Muhammad Babar","doi":"10.1007/s12012-024-09913-x","DOIUrl":"10.1007/s12012-024-09913-x","url":null,"abstract":"<p><p>Cardiovascular diseases (CVD), primarily ischemic heart disease and stroke, remain leading global health burdens. Environmental risk factors have a major role in the development of CVD, particularly exposure to heavy metals. The Triglyceride Glucose Index (TyG), a measure of insulin resistance and CVD risk, is the primary focus of this study, which summarizes the most recent findings on the effects of lead (Pb), arsenic (As), and cadmium (Cd) on CVD risk. A higher risk of CVD is correlated with an elevated TyG index, which has been linked to insulin resistance. Exposure to Cd is associated with disturbance of lipid metabolism and oxidative stress, which increases the risk of CVD and TyG. Exposure reduces insulin secretion and signaling, which raises the TyG index and causes dyslipidemia. Pb exposure increases the risk of CVD and TyG index via causing oxidative stress and pancreatic β-cell destruction. These results highlight the need of reducing heavy metal exposure by lifestyle and environmental modifications in order to lower the risk of CVD. To comprehend the mechanisms and create practical management plans for health hazards associated with heavy metals, more study is required.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1301-1309"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104710","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":"Rhein Alleviates Doxorubicin-Induced Myocardial Injury by Inhibiting the p38 MAPK/HSP90/c-Jun/c-Fos Pathway-Mediated Apoptosis.","authors":"Yong Chen, Yadan Tu, Jin Cao, Yigang Wang, Yi Ren","doi":"10.1007/s12012-024-09917-7","DOIUrl":"10.1007/s12012-024-09917-7","url":null,"abstract":"<p><p>Doxorubicin (Dox) has been limited in clinical application due to its cardiac toxicity that varies with the dose. This study aimed to explore how Rhein modulates Dox-induced myocardial toxicity. The general condition and echocardiographic changes of mice were observed to evaluate cardiac function and structure, with myocardial cell injury and apoptosis checked by TUNEL and HE staining. The ELISA assessed markers of myocardial damage and inflammation. The TCMSP and SwissTargetPrediction databases were used to retrieve Rhein's targets while GeneCards was used to find genes related to Dox-induced myocardial injury. Intersection genes were analyzed by Protein-Protein Interaction Networks. The core network genes underwent GO and KEGG enrichment analysis using R software. Western blot was used to detect protein expression. Compared to the Dox group, there was no remarkable difference in heart mass /body mass ratio in the Rhein+Dox group. However, heart mass/tibia length increased. Mice in the Rhein+Dox group had significantly increased LVEF, LVPWs, and LVFS compared to those in the Dox group. Myocardial cell damage, inflammation, and apoptosis significantly reduced in the Rhein+Dox group compared to the model group. Eleven core network genes were selected. Further, Rhein+Dox group showed significantly downregulated expression of p38/p-p38, HSP90AA1, c-Jun/p-c-Jun, c-Fos/p-c-Fos, Bax, and cleaved-caspase-3/caspase-3 while Bcl-2 expression significantly upregulated compared to the Dox group. The study suggests that Rhein mediates cardioprotection against Dox-induced myocardial injury, at least partly, by influencing multiple core genes in the MAPK signaling pathway to inhibit myocardial cell apoptosis.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1139-1150"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139393","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":"Therapeutic Efficacy of Selenium Pre-treatment in Mitigating Cadmium-Induced Cardiotoxicity in Zebrafish (Danio rerio).","authors":"Rachael M Heuer, Priscila Falagan-Lotsch, Jessica Okutsu, Madison Deperalto, Rebekka R Koop, Olaedo G Umeh, Gabriella A Guevara, Md Imran Noor, Myles A Covington, Delia S Shelton","doi":"10.1007/s12012-024-09910-0","DOIUrl":"10.1007/s12012-024-09910-0","url":null,"abstract":"<p><p>Cardiovascular diseases are a rampant public health threat. Environmental contaminants, such as Cadmium (Cd), a toxic metal, are risk factors for cardiovascular diseases. Given that human exposure to Cd is increasing, there is a need for therapies to ameliorate Cd toxicity. Selenium (Se), an essential trace element, has been proposed to rescue the effects of Cd toxicity, with mixed effects. Se's narrow therapeutic window necessitates precise dosing to avoid toxicity. Here, we assessed the effects of various waterborne Cd and Se concentrations and sequences on cardiac function using zebrafish (Danio rerio). We showed that Cd induced pericardial edemas and modified heart rates in zebrafish larvae in a concentration-dependent manner. To identify the therapeutic range of Se for Cd-induced cardiotoxicity, zebrafish embryos were treated with 0, 10, 50, 100, 150, or 200 μg/L Se for 1-4 days prior to exposure to 2.5 and 5 μg/L Cd. We found that a 50 µg/L Se pre-treatment before 2.5 μg/L Cd, but not 5 μg/L Cd, reduced the prevalence of pericardial edemas and ameliorated Cd-induced bradycardia in zebrafish. Zebrafish exposed to 10 and 50 μg/L of Se for up to 4 days showed typical heart morphology, whereas other Se-exposed and control fish presented pericardial edemas. Longer Se pre-treatment durations led to fewer incidences of pericardial edemas. Overall, this study highlights the importance of optimizing Se concentrations and pre-treatment periods to harness its protective effects against Cd-induced cardiotoxicity. These findings provide insights into potential therapeutic strategies for reducing Cd-related cardiovascular damage in humans.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1287-1300"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104711","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":"Sevoflurane Affects Myocardial Autophagy Levels After Myocardial Ischemia Reperfusion Injury via the microRNA-542-3p/ADAM9 Axis.","authors":"Jiying Ao, Xueting Zhang, Degang Zhu","doi":"10.1007/s12012-024-09908-8","DOIUrl":"10.1007/s12012-024-09908-8","url":null,"abstract":"<p><p>This research focused on investigating the effects of sevoflurane (Sev) on myocardial autophagy levels after myocardial ischemia reperfusion (I/R) injury via the microRNA-542-3p (miR-542-3p)/ADAM9 axis. Mice underwent 30 min occlusion of the left anterior descending coronary (LAD) followed by 2 h reperfusion. Cardiac infarction was determined by 2,3,5-triphenyltetrazolium chloride triazole (TTC) staining. Cardiac function was examined by echocardiography. Cardiac markers and oxidative stress factors were evaluated by ELISA. Autophagy-associated factors were detected by western blot. Relationship between miR-542-3p and ADAM9 was tested by dual-luciferase reporter gene assay, RT-qPCR, and western blot. Sev treatment ameliorated cardiac dysfunction, myocardial oxidative stress, and histopathological damages, decreased myocardial infarction size and myocardial apoptotic cells after myocardial I/R injury. Sev treatment elevated miR-542-3p expression and decreased ADAM9 expression in myocardial tissues after myocardial I/R injury. miR-542-3p overexpression could enhance the ameliorative effects of Sev on myocardial injury and myocardial autophagy in I/R mice. miR-542-3p targeted and negatively regulated ADAM9 expression. ADAM9 overexpression reversed the ameliorative effects of miR-542-3p up-regulation on myocardial injury and myocardial autophagy in Sev-treated I/R mice. Sev treatment could ameliorate myocardial injury and myocardial autophagy in I/R mice, mediated by mechanisms that include miR-542-3p up-regulation and ADAM9 down-regulation.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1226-1235"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911863","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":"High Mobility Group Box 1 and Cardiovascular Diseases: Study of Act and Connect.","authors":"Rufaida Wasim, Aditya Singh, Anas Islam, Saad Mohammed, Aamir Anwar, Tarique Mahmood","doi":"10.1007/s12012-024-09919-5","DOIUrl":"10.1007/s12012-024-09919-5","url":null,"abstract":"<p><p>Cardiovascular disease is the deadly disease that can result in sudden death, and inflammation plays an important role in its onset and progression. High mobility group box 1 (HMGB1) is a nuclear protein that regulates transcription, DNA replication, repair, and nucleosome assembly. HMGB1 is released passively by necrotic tissues and actively secreted by stressed cells. Extracellular HMGB1 functions as a damage associated molecular patterns molecule, producing numerous redox forms that induce a range of cellular responses by binding to distinct receptors and interactors, including tissue inflammation and regeneration. Extracellular HMGB1 inhibition reduces inflammation and is protective in experimental models of myocardial ischemia/reperfusion damage, myocarditis, cardiomyopathies caused by mechanical stress, diabetes, bacterial infection, or chemotherapeutic drugs. HMGB1 administration following a myocardial infarction followed by permanent coronary artery ligation improves cardiac function by stimulating tissue regeneration. HMGB1 inhibits contractility and produces hypertrophy and death in cardiomyocytes, while also stimulating cardiac fibroblast activity and promoting cardiac stem cell proliferation and differentiation. Maintaining normal nuclear HMGB1 levels, interestingly, protects cardiomyocytes from apoptosis by limiting DNA oxidative stress, and mice with HMGB1cardiomyocyte-specific overexpression are partially protected from cardiac injury. Finally, elevated levels of circulating HMGB1 have been linked to human heart disease. As a result, following cardiac damage, HMGB1 elicits both detrimental and helpful responses, which may be due to the formation and stability of the various redox forms, the particular activities of which in this context are mostly unknown. This review covers recent findings in HMGB1 biology and cardiac dysfunction.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":" ","pages":"1268-1286"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145274","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}