Journal of Cardiovascular Translational Research最新文献

{"title":"RNA Therapies in Cardio-Kidney-Metabolic Syndrome: Advancing Disease Management.","authors":"Abbas Mohammadi, Azin Karimian, Kasra Shokri, Ashkan Mohammadi, Nazanin Hazhir-Karzar, Rayeheh Bahar, Azar Radfar, Mohammadreza Pakyari, Behnam Tehrani","doi":"10.1007/s12265-025-10603-4","DOIUrl":"https://doi.org/10.1007/s12265-025-10603-4","url":null,"abstract":"<p><p>Cardio-Kidney-Metabolic (CKM) Syndrome involves metabolic, kidney, and cardiovascular dysfunction, disproportionately affecting disadvantaged groups. Its staging (0-4) highlights the importance of early intervention. While current management targets hypertension, heart failure, dyslipidemia, and diabetes, RNA-based therapies offer innovative solutions by addressing molecular mechanisms of CKM Syndrome. Emerging RNA treatments, including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), show promise in slowing disease progression across CKM stages. For example, ASOs and siRNAs targeting ApoC-III and ANGPTL3 reduce triglycerides and LDL cholesterol, while siRNAs improve blood pressure control by targeting the renin-angiotensin-aldosterone system. Obesity treatments leveraging miRNAs and circRNAs tackle a key CKM risk factor. In heart failure and diabetes, RNA-based therapies improve cardiac function and glucose control, while early kidney disease trials show potential for RNAi in acute injury. Further research is essential to refine these therapies and ensure equitable access.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624877","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":"Human Cardiac Microtissues Display Improved Engraftment and Survival in a Porcine Model of Myocardial Infarction.","authors":"Evelyne Demkes, Aina Cervera-Barea, Patricia Ebner-Peking, Martin Wolf, Sarah Hochmann, Amy S Scheren, Mayke Bijsterveld, C Marlies van Oostveen, Marlijn Jansen, Joyce Visser, Wiebke Triebert, Caroline Halloin, Johannes G G Dobbe, Judith de Vos, Melanie Schürz, Joachim Danmayr, Maurice C G Aalders, Gerard J J Boink, Klaus Neef, Dirk Strunk, Robert Zweigerdt, Saskia C A de Jager, Joost P G Sluijter","doi":"10.1007/s12265-025-10596-0","DOIUrl":"https://doi.org/10.1007/s12265-025-10596-0","url":null,"abstract":"<p><p>Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) constitute a promising therapy for myocardial infarction (MI). The lack of an effective immunosuppressive regimen, combined with single-cell transplantations, results in suboptimal outcomes, such as poor engraftment and compromised therapeutic efficacy. This study aimed to confirm the increased retention of hiPSC-CMs microtissues (CMTs) over single-cell grafts. To ensure the long-term survival of CMTs for potential cardiac applications, CMTs were transplanted in a porcine model of MI using a triple immunosuppression protocol designed to limit immune cell infiltration. Acute evaluation of spherical hiPSC-CMs aggregates and dissociated aggregates followed by the development of a triple immunosuppression protocol were performed in healthy animals. Long-term survival of CMTs was later examined in pigs that underwent a transient coronary occlusion. Two weeks post-MI, the immunosuppression treatment was initiated and on day 28 the animals were transplanted with CMTs and followed for four more weeks. Acutely, CMTs showed superior retention compared to their dissociated counterparts. The immunosuppression regimen led to no organ damage and stable levels of circulating drugs once optimal dose was achieved. Two weeks post-xenotransplantation in healthy pigs, histology revealed that immunosuppressed animals displayed a significant decrease in total cellular infiltrates, particularly in CD3⁺ T cells. Pigs that underwent coronary occlusion, which later were immunosuppressed and treated with CMTs (5 × 10⁷ cells), showed cell engraftment onto the native myocardium four weeks post-transplantation. This study supports the use of a triple immunosuppression cocktail to ensure long-term survival of CMTs for the treatment of MI.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624873","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 Dual Latex Balloon Catheter for Temporarily Closing Acute Postinfarction Ventricle Septum Defect (VSD) in a Pig Model.","authors":"Hua-Di Qin, Yang Yang, Fei Xie, Lin Hou, Hui Gao, Jing-Wei Tang, Xiang-Sen Shao, Chun-Chang Qin","doi":"10.1007/s12265-025-10601-6","DOIUrl":"https://doi.org/10.1007/s12265-025-10601-6","url":null,"abstract":"<p><p>Acute postinfarction ventricular septum defect has a persistently high mortality rate due to unstable scars in the acute phase, which make surgery or occluder use unsuitable. Delayed closure increases the risk of irreversible hemodynamic deterioration. To address this, a dual latex balloon catheter was designed for temporary closure and tested in a pig model. The catheter, with a 10 French profile and 80 cm in length, includes two independent latex balloons and an anticoagulant channel to prevent thrombus formation. It was inserted via the jugular vein and guided over a 0.014-inch wire to straddle and seal the ventricular septum defect. In eight Yorkshire pigs with ventricular septum defects and acute myocardial infarction, the catheter effectively closed defects ranging from 6.1 to 10.5 mm for two weeks without complications. This innovative tool shows promise as a bridge therapy for managing acute postinfarction ventricular septum defect and warrants further evaluation.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615560","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":"New Types of Post-Translational Modification of Proteins in Cardiovascular Diseases.","authors":"Juntao Fang, Shaoyu Wu, Hengli Zhao, Chuanmeng Zhou, Ling Xue, Zhiyong Lei, Hui Li, Zhixin Shan","doi":"10.1007/s12265-025-10600-7","DOIUrl":"https://doi.org/10.1007/s12265-025-10600-7","url":null,"abstract":"<p><p>Post-translational modifications (PTMs), which are covalent alterations of proteins after their synthesis, are critical for their proper function and the maintenance of cellular physiology. The significance of PTMs in the context of cardiovascular diseases (CVDs) has been increasingly recognized due to their potential to influence protein stability, activity, and localization, thereby affecting the progression of CVDs. The identification and understanding of PTMs in CVDs at the molecular level are vital for the discovery of new biomarkers and new targets for clinical interventions. This article provides a comprehensive overview of the role and mechanisms of new types of PTMs, such as acetylation, crotonylation, succinylation, S-nitrosylation, malonylation, S-palmitonylation, β-hydroxybutyrylation and lactylation, in CVDs, highlighting their importance in advancing diagnostic and therapeutic approaches for CVDs.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542071","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":"Apelin13 Loaded Nano-Niosomes Confer Cardioprotection in a Rat Model of Myocardial Ischemia Reperfusion by Targeting the Nrf2/HO-1 Pathway.","authors":"Neda Tekiyeh Maroof, Saeed Mehrzadi, Maryam Naseroleslami, Nahid Aboutaleb","doi":"10.1007/s12265-025-10597-z","DOIUrl":"https://doi.org/10.1007/s12265-025-10597-z","url":null,"abstract":"<p><p>Although apelin-13 has cardioprotective impact, its short half-life in the bloodstream has challenged its clinical application. Using nanocarriers can increase the bioavailability, functionality, and stability of drugs. Current investigation aims to find whether apelin13-loaded nano-niosomes confer cardioprotection in an animal model of myocardial ischemia/reperfusion injury (MI/R) via suppressing ferroptosis, targeting Nrf2 pathway, and AMPK/GSK-3β axis. Ligation of the left anterior coronary artery descending was done to establish the MI/R model and 15 μg/kg of apelin13-loaded nano-niosomes were intramyocardially administrated. Echocardiography, RT-PCR, immunohistochemistry, western blot, ELISA kits, and H&E staining were applied to measure the related indicators. Treatment with both apelin13 and apelin13 loaded nano-niosomes could improve cardiac function and attenuate oxidative stress, myocardial inflammatory factors, and hence ferroptosis by activating the Nrf2 and its downstream proteins HO1, NQO1, AMPK/GSK-3β signaling pathway. In conclusion, apelin13-loaded nano-niosomes are effective MI therapeutic agents against MI/R-induced ferroptosis by activation of Nrf2 via AMPK/GSK-3β axis.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458135","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":"Sensitivity of Left Atrial Flow Dynamics to Echocardiographic and Computed Tomography Data.","authors":"Ahmad Bshennaty, Brennan J Vogl, Ghasaq Saleh, Agata Sularz, Mohamad Alkhouli, Hoda Hatoum","doi":"10.1007/s12265-025-10598-y","DOIUrl":"https://doi.org/10.1007/s12265-025-10598-y","url":null,"abstract":"<p><p>Computational simulations are a powerful tool in the understanding, diagnosing, and treatment of cardiovascular diseases. Incomplete clinical data often limits computational assessment, which may lead to inaccuracies. This study aims to assess the sensitivity of left atrial flow dynamics to echocardiographic and computed tomography data. Models of the LA were reconstructed at the E-wave(Geometry 1)and end-diastolic(Geometry 2)phases from CT scans. CFD simulations were carried out using 3 different sets of BCs. BC2 and BC3 presented similar results that were significantly different from BC1. The effect from the choice of geometry was significant with BC2 and BC3 but minor with BC1. Differences in parameters across the simulated cases highlight the importance of using consistent BCs and geometries for CFD studies. Acquiring the pressure in the LA does not seem to be necessary for the accuracy of CFD simulations. Validation of all simulations indicates reliable patient-specific results.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458137","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":"Resonance Raman Spectroscopy Detects Ischemia in Experimental Coarctation of the Aorta in a Rodent Model.","authors":"Alyssa R Thomas, Kristen Lazelle, Julia Garcia Mancebo, Padraic Romfh, John N Kheir","doi":"10.1007/s12265-025-10599-x","DOIUrl":"10.1007/s12265-025-10599-x","url":null,"abstract":"<p><p>Coarctation of the aorta (CoA) can cause aortic obstruction, ischemia, and death. Resonance Raman Spectroscopy (RRS) measures tissue oxyhemoglobin (ShbO₂) and mitochondrial redox state (3RMR) non-invasively. Metal wire was placed around the aorta of Sprague Dawley rats to generate a systolic blood pressure (SBP) gradient. RRS-ShbO₂ and 3RMR were measured pre- (hand) and post-obstruction (foot). In model 1 (n = 8), the gradient rapidly reached 120 mmHg. In model 2 (n = 30), gradients of 20 mmHg (n = 9) and 40 mmHg (n = 12) were maintained for 2 h. In model 1, foot-ShbO₂ and 3RMR changed significantly (P = 0.004 and P = 0.007) at SBP gradients of 80-mmHg or above. In model 2, the 40-mmHg gradient group showed significant declines in foot-ShbO2 (P = 0.014) and increases in 3RMR (P = 0.008) by 1 h. Foot-ShbO₂ and 3RMR correlated strongly with serum mixed venous saturation (ShbO₂: r = 0.73, P < 0.0001; 3RMR: r = -0.55, P < 0.0001). RRS effectively detects ischemia caused by aortic obstruction in a CoA model.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458136","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":"Targeting KDM4C Prevents Heart Failure after Acute Myocardial Infarction Via Activation of SOS2.","authors":"Caiping Tan, Xiaoqi Chen, Lingqi Xu, Jiaping Chen, Yingbing Tu","doi":"10.1007/s12265-025-10594-2","DOIUrl":"https://doi.org/10.1007/s12265-025-10594-2","url":null,"abstract":"<p><p>Here, we focused on the function of SOS2 in heart failure (HF) after acute myocardial infarction (AMI) and investigated the mechanism. An oxygen-glucose deprivation (OGD) model in HL-1 cardiomyocytes and the ligation of the left anterior descending coronary artery in mice were conducted for MI modeling. SOS2 was downregulated in the heart tissues of mice with AMI. SOS2 activated the PI3K/Akt signaling, thereby alleviating cardiomyocyte apoptosis and inflammatory response, which were compromised by PI3K/Akt signaling inhibitor LY294002. Lysine-specific demethylase 4C (KDM4C) levels were downregulated in the heart tissue of AMI mice and OGD-induced HL-1 cells, accompanied by a reduction in H3K9Me3, while KDM4C overexpression triggered SOS2 expression by removing H3K9Me3 modification from its promoter. Knockdown of SOS2 abated the effects of KDM4C overexpression, thereby accentuating HF in mice. This study revealed that KDM4C protected mice against HF following AMI by restoration of SOS2 and the PI3K/Akt signaling.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122910","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":"Shorter Leukocyte Telomere Length Is Associated with Increased Major Adverse Cardiovascular Events or Mortality in Patients with Essential Hypertension.","authors":"Hongna Fu, Yuanting Zhu, Luyang Lin, Peng Jiang, Guoyi Cai, Lijin Zeng, Xinyu Li, Yuchun Zhang, Chunhao Li, Hong Zhan, Bo Zhang, Zhen Yang","doi":"10.1007/s12265-024-10558-y","DOIUrl":"10.1007/s12265-024-10558-y","url":null,"abstract":"<p><p>The association between leukocyte telomere length (LTL) alteration and major adverse cardiovascular events (MACE) or mortality in patients with hypertension is still unclear. 20,034 patients with essential hypertension were enrolled from UK biobank. Multivariable COX regression models were performed to assess the association. LTL was shorter in hypertensive patients with MACE compared to those without MACE. Hypertensive patients in the lowest LTL quartile were at higher risk to develop MACE (adjusted HR 1.15 [95% CI 1.02-1.29], vs top LTL quartile, p-trend = 0.03). Similarly, shorter LTL was related with increased mortality (adjusted HR 1.18[95% CI 1.06-1.3], lowest vs top LTL quartile, p-trend < 0.001). This investigation demonstrated that shorter LTL is associated with increased risk of MACE or mortality in patients with essential hypertension, which indicates that LTL may be a potential predictor of prognosis or underlying therapeutic target for hypertension.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"198-208"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466386","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":"Past Trends and Future Directions of Cardiac Regenerative Medicine - A Systematic Analysis of Clinical Trial Registries.","authors":"Maaike Wulfse, Mats T Vervoorn, Jantijn J G J Amelink, Elisa M Ballan, Saskia C A de Jager, Joost P G Sluijter, Pieter A Doevendans, Peter-Paul M Zwetsloot, Niels P Van der Kaaij","doi":"10.1007/s12265-024-10563-1","DOIUrl":"10.1007/s12265-024-10563-1","url":null,"abstract":"<p><p>Cell therapy, gene therapy, and tissue engineering have been explored as potential strategies to repair or regenerate damaged cardiac tissue. Despite the presence of encouraging preclinical data, clinical trials of regenerative cardiac therapies have yielded mixed results. Our study aimed to investigate the fate of all registered clinical trials within regenerative cardiac medicine, with the purpose of exploring the potential role of publication bias (or trial-completion bias), how published and unpublished research affects the field, and to draw lessons and recommendations for future clinical trials. In this analysis, we show that only a third of all registered trials has yielded results and that a significant number of trials are not completed. Furthermore, we identified significant heterogeneity in study design, study phase, funding, specific therapies used, primary outcome measures and methods of outcome assessment. These observations might hinder the successful translation of cardiac regenerative therapies into clinical practice.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"209-220"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365371","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}