{"title":"Isolated Perfused Hearts for Cardiovascular Research: An Old Dog with New Tricks.","authors":"Tianshuo Yang, Zirui Liu, Songren Shu, Zhice Chen, Xiumeng Hua, Jiangping Song","doi":"10.1007/s12265-024-10517-7","DOIUrl":"10.1007/s12265-024-10517-7","url":null,"abstract":"<p><p>In modern cardiovascular research, isolated perfused hearts have become cost-effective and highly reproducible tools to investigate the mechanisms of cardiovascular diseases (CVDs). Since they were first introduced in the nineteenth century, isolated perfused hearts have been extensively used for testing novel therapies, elucidating cardiac metabolic and electrophysiological activities, and modeling CVDs, including ischemic heart disease, arrhythmias, and hyperacute rejection. In recent years, ex vivo heart perfusion (EVHP) has shown potential in cardiac transplantation by allowing prolonged preservation and reconditioning of donor hearts. In this review, we summarize the evolution of the isolated perfused heart technique and its applications in cardiovascular research to help researchers comprehensively understand the capabilities of isolated heart models and provide guidance to use them to investigate various CVDs.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1207-1217"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876458","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":"Differential Expression of mRNA in Peripheral Blood Mononuclear Cells May Predict Postoperative Atrial Fibrillation in Coronary Artery Bypass Surgery Patients.","authors":"Mingqi Tan, Xiankun Liu, Lianqun Wang, Nan Jiang, Yunpeng Bai, Zhigang Guo","doi":"10.1007/s12265-024-10524-8","DOIUrl":"10.1007/s12265-024-10524-8","url":null,"abstract":"<p><p>Postoperative Atrial Fibrillation (POAF) frequently follows Coronary Artery Bypass Grafting (CABG) surgery. This prospective study investigates genes linked to POAF in CABG patients, aiming to create a predictive model. Employing differential gene and methylation analyses, the study identified four genes (WARS2, CKAP2, CHI3L1, HSD17B6) associated with POAF. Preoperative plasma samples and clinical data were collected from 139 CABG patients, categorized into POAF (+) (43) and POAF (-) (96). Real-time quantitative PCR assessed gene expression, and a predictive model using the LASSO method demonstrated robust performance, with AUC values of 0.8895 in the training set and 0.7840 in the test set. This pioneering study integrates genomics and clinical data, suggesting WARS2, CKAP2, and CHI3L1 as potential indicators for POAF prediction.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1193-1204"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620081","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}
Andrea Villatore, Antonella Monno, Clara Sciorati, Patrizia Rovere-Querini, Simone Sala, Davide Carino, Michele De Bonis, Domenico Cianflone, Angelo A Manfredi, Giovanni Peretto
{"title":"Pentraxin 3 in Myocarditis: Proof-of-Principle Assessment as a Diagnostic and Prognostic Biomarker.","authors":"Andrea Villatore, Antonella Monno, Clara Sciorati, Patrizia Rovere-Querini, Simone Sala, Davide Carino, Michele De Bonis, Domenico Cianflone, Angelo A Manfredi, Giovanni Peretto","doi":"10.1007/s12265-024-10506-w","DOIUrl":"10.1007/s12265-024-10506-w","url":null,"abstract":"<p><p>Pentraxin 3 (PTX3) is an acute phase protein produced in various tissues in response to microbial and sterile stimuli, which regulates the inflammation outcomes. PTX3 has not been investigated in myocarditis. Our aim was to assess circulating and cardiac tissue expression of PTX3 in 55 patients with myocarditis proven by magnetic resonance and/or endomyocardial biopsy. A major proportion of patients with myocarditis displayed significantly increased plasma PTX3 levels as compared with controls (26/30 vs. 0/10), with higher diagnostic yield than conventional biomarkers in the study group. Cardiac tissue analysis revealed PTX3 expression in all patients (40/40), with viral myocarditis exhibiting higher signal intensity than autoimmune myocarditis, and with a predominant localization in cardiomyocytes. Abnormal plasma PTX3 was associated with systolic dysfunction and heart failure at presentation. Interestingly, patients who recovered by 12 months had higher baseline PTX3 levels. Our preliminary data support the potential use of PTX3 as a biomarker in myocarditis.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1048-1058"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318365","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}
Phillip van Dijck, Carmen Hannemann, Henryk Dreger, Verena Stangl, Karl Stangl, Antje Ludwig, Bernd Hewing
{"title":"Increased Expression of Inactive Rhomboid Protein 2 in Circulating Monocytes after Acute Myocardial Infarction.","authors":"Phillip van Dijck, Carmen Hannemann, Henryk Dreger, Verena Stangl, Karl Stangl, Antje Ludwig, Bernd Hewing","doi":"10.1007/s12265-024-10519-5","DOIUrl":"10.1007/s12265-024-10519-5","url":null,"abstract":"<p><p>Increased TNF-α levels following acute myocardial infarction (AMI) contribute to impaired recovery of myocardial function. Interaction of inactive rhomboid protein 2 (iRhom2) with TNF-α converting enzyme (TACE) is required for TNF-α shedding from immune cells. We hypothesized that iRhom2 expression increases in circulating monocytes following AMI. Transcript levels of iRhom2, TACE and TNF-α were evaluated by quantitative real-time PCR in isolated monocytes of 50 AMI patients at admission (d1) and 3 days (d3) after. We observed a significant increase in levels of iRhom2 mRNA expression in monocytes between d1-3, while TNF-α and TACE mRNA expression remained unchanged. At d3, iRhom2 mRNA expression positively correlated with levels of intermediate monocytes or serum TNF-α, and negatively with LV systolic function. iRhom2 may contribute to regulation of post-infarction inflammation and is associated with LV dysfunction following AMI. iRhom2 modulation should be evaluated as a potential therapeutic strategy to attenuate cardiac remodeling following AMI.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1059-1066"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922360","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":"Vaccarin Ameliorates Doxorubicin-Induced Cardiotoxicity via Inhibition of p38 MAPK Mediated Mitochondrial Dysfunction.","authors":"Xin Shi, Yang Cao, Hongyu Wang, Qi Zhao, Cong Yan, Shengzhu Li, Ling Jing","doi":"10.1007/s12265-024-10525-7","DOIUrl":"10.1007/s12265-024-10525-7","url":null,"abstract":"<p><p>Doxorubicin is a frequently used chemotherapeutic agent for treating various malignancies. However, it leads to severe cardiotoxic side effects, such as heart failure, and elevates the risk of sudden cardiac death among cancer patients. While oxidative stress has been identified as the primary cause of doxorubicin-induced cardiotoxicity, therapeutic antioxidant approaches have yielded unsatisfactory outcomes. The aim of this study is to explore the therapeutic potential of vaccarin, an active flavonoid glycoside extracted from traditional Chinese herbal agent Semen Vaccariae, in doxorubicin-induced cardiotoxicity. We observed that vaccarin significantly ameliorates doxorubicin-induced heart dysfunction in mouse model and suppresses oxidative stress mediated cell apoptosis via specifically inhibiting the activation of p38 MAPK pathway. In vitro, we observed that vaccarin alleviates doxorubicin-induced mitochondrial membrane depolarization and ROS generation in H9c2 cell, but the p38 MAPK agonist anisomycin reverses these effects. Our findings provide a promising natural antioxidant to protect against DOX-induced cardiotoxicity.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1155-1171"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419254","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":"Pathogenic Autoimmunity in Atherosclerosis Evolves from HSP60-Reactive CD4 + T Cells.","authors":"Shixiang Wang, Yongquan Chen, Danyan Zhou, Jiawei Zhang, Guofeng Guo, Youquan Chen","doi":"10.1007/s12265-024-10516-8","DOIUrl":"10.1007/s12265-024-10516-8","url":null,"abstract":"<p><p>Clinical evidence suggests anti-Hsp60 antibodies could contribute to atherosclerosis (AS) development, with unclear mechanisms. This study aims to explore the role of anti-HSP60-mediated autoimmunity in AS progression. HSP60-MHC tetramers were used to characterize HSP60-specific CD4 + T cells and assess TCR responses in mice. These cells were transplanted into AS mice to examine immune cell differentiation and infiltration in plaques and blood. Mice were injected with recombinant HSP60 or anti-HSP60 sera to evaluate effects on plaque progression and macrophage activity. Experiments with muMT<sup>-/-</sup>Apoe<sup>-/-</sup> mice examined humoral immunity's role in this autoimmunity. HSP60-reactive CD4 + T cells in AS mice differentiated into follicular helper cells, not Th1/Th17. Anti-HSP60 treatments increased macrophage infiltration and M1 polarization, indicating an anti-HSP60-driven inflammatory progression, dependent on humoral immunity. Anti-HSP60 influences macrophage infiltration, polarization, and plaque formation via humoral immunity, shedding light on its potential role in AS progression.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1172-1180"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065351","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":"Inhibition of METTL4: Targeting a Methyltransferase that Alleviates Heart Failure by Modulating Excess N6-Methyladenine in Mitochondrial DNA.","authors":"Jiaqi Wang, Michail Spanos, Yihua Bei","doi":"10.1007/s12265-024-10535-5","DOIUrl":"10.1007/s12265-024-10535-5","url":null,"abstract":"","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1205-1206"},"PeriodicalIF":2.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590429","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":"A Novel Swine Model for Inducing Functional Tricuspid Valve Regurgitation.","authors":"Dawei Lin, Peng Zhang, Yongchao Zhao, Wanjiao Chen, Dandan Chen, Xiaochun Zhang, Daxin Zhou, Junbo Ge","doi":"10.1007/s12265-024-10510-0","DOIUrl":"10.1007/s12265-024-10510-0","url":null,"abstract":"<p><p>Functional tricuspid regurgitation (FTR) is the most common TR, although experimental models to effectively study it are scarce; therefore, this study aimed to establish a robust experimental swine model. A swine FTR model was developed using radiofrequency ablation, atrial septostomy, and right atrial volume overload. The baseline and follow-up echocardiography was performed to evaluate the progression FTR and changes in the heart. Autopsy was employed to verify the anatomy of tricuspid valve. One-month post intervention, among the subjects, one (8.3%) exhibited severe FTR, eight (66.7%) exhibited moderate TR, and three (25%) exhibited mild FTR. Each pig developed an atrial septal defect (diameter, 1.5 ± 0.5 cm). The tricuspid annular diameter significantly increased with enlargement of right heart (P < 0.05). No significant difference was found on left heart size and mitral regurgitation. We successfully developed a novel swine FTR model, providing a reliable and effective platform for further research on FTR.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1004-1010"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944927","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}
Radosław Wilimski, Jan Budzianowski, Michał Łomiak, Anna Olasińska-Wiśniewska, Katarzyna Pieniak, Szymon Jędrzejczyk, Olaf Domaszk, Magdalena Chudzik, Krzysztof J Filipiak, Jarosław Hiczkiewicz, Wojciech Faron, Tomasz Urbanowicz, Marek Jemielity, Marek Grygier, Marcin Grabowski, Mariusz Kuśmierczyk, Bartosz Rymuza, Zenon Huczek, Janusz Kochman, Edwin van der Pol, Rienk Nieuwland, Aleksandra Gąsecka
{"title":"Extracellular Vesicles to Predict Outcomes After Transcatheter Aortic Valve Implantation - a Prospective, Multicenter Cohort Study.","authors":"Radosław Wilimski, Jan Budzianowski, Michał Łomiak, Anna Olasińska-Wiśniewska, Katarzyna Pieniak, Szymon Jędrzejczyk, Olaf Domaszk, Magdalena Chudzik, Krzysztof J Filipiak, Jarosław Hiczkiewicz, Wojciech Faron, Tomasz Urbanowicz, Marek Jemielity, Marek Grygier, Marcin Grabowski, Mariusz Kuśmierczyk, Bartosz Rymuza, Zenon Huczek, Janusz Kochman, Edwin van der Pol, Rienk Nieuwland, Aleksandra Gąsecka","doi":"10.1007/s12265-024-10521-x","DOIUrl":"10.1007/s12265-024-10521-x","url":null,"abstract":"<p><strong>Introduction: </strong>Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at intermediate and high surgical risk. Circulating extracellular vesicles (EVs) are nanoparticles involved in cardiovascular diseases. We aimed to (i) determine the effect of TAVI on plasma concentrations of five EV subtypes and (ii) evaluate the predictive value of EVs for post-TAVI outcomes.</p><p><strong>Methods: </strong>Blood samples were collected 1 day before TAVI and at hospital discharge. Concentrations of EVs were evaluated using flow cytometry.</p><p><strong>Results: </strong>Concentration of leukocytes EVs decreased after TAVI, compared to the measurement before (p = 0.008). Among 123 patients discharged from the hospital, 19.5% experienced MACCE during the median of 10.3 months. Increased pre-TAVI concentration of phosphatidylserine-exposing EVs was an independent predictor of MACCE in multivariable analysis (OR 5.313, 95% CI 1.164-24.258, p = 0.031).</p><p><strong>Conclusions: </strong>Patients with increased pre-TAVI concentration of procoagulant, PS-exposing EVs have over fivefold higher odds of adverse outcomes.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"992-1003"},"PeriodicalIF":4.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160041","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}