Journal of Cardiovascular Translational Research最新文献

{"title":"Mesenchymal Stem Cell-based Apelin Gene Therapy Improves Pulmonary Artery Remodeling in Monocrotaline-induced Pulmonary Hypertension Through PI3K/AKT/eNOS and ERK1/2 Signaling Pathways.","authors":"Li Wang, Weijian Wang, Ting Wu, Liang Chen, Gangjun Zong","doi":"10.1007/s12265-025-10612-3","DOIUrl":"https://doi.org/10.1007/s12265-025-10612-3","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) poses a challenge due to limited curative options and ineffective treatments. Mesenchymal stem cell (MSC) therapy has emerged as a potential intervention for PAH. This study delved into the therapeutic potential and molecular mechanisms underlying MSC-based apelin gene therapy in PAH rats induced by monocrotaline (MCT). Wharton's jelly-derived MSCs transfected with pcSLenti-APLN were utilized as therapeutic agents. Transplanted MSCs successfully homed to the lung tissue of rats and sustained survival for at least three weeks. MSC-mediated apelin gene therapy effectively reduced pulmonary artery pressure, mitigated pulmonary vascular remodeling, and modulated apoptosis in MCT-induced PAH rats. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) and ERK1/2 signaling pathways were involved in the therapeutic effects. Meanwhile, Apelin-MSCs also regulated MCT-induced changes of Bax and Bcl-2 in the lung lobes and pulmonary arterioles. MSC-based apelin gene therapy could be considered a possible therapeutic strategy for PAH.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Mitophagy in Cardiac Metabolic Remodeling of Heart Failure: Insights of Molecular Mechanisms and Therapeutic Prospects.","authors":"Fangying Yan, Liwen Bao","doi":"10.1007/s12265-025-10606-1","DOIUrl":"https://doi.org/10.1007/s12265-025-10606-1","url":null,"abstract":"<p><p>Heart failure (HF) treatment remains one of the major challenges in cardiovascular disease management, and its pathogenesis requires further exploration. Cardiac metabolic remodeling is of great significance as a key pathological process in the progression of HF. The complex alterations of metabolic substrates and associated enzymes in mitochondria create a vicious cycle in HF. These changes lead to increased reactive oxygen species, altered mitochondrial Ca²⁺ handling, and the accumulation of fatty acids, contributing to impaired mitochondrial function. In this context, mitophagy plays a significant role in clearing damaged mitochondria, thereby maintaining mitochondrial function and preserving cardiac function by modulating metabolic remodeling in HF. This article aims to explore the role of mitophagy in cardiac metabolic remodeling in HF, especially in obesity cardiomyopathy, diabetic cardiomyopathy, and excessive afterload-induced heart failure, thoroughly analyze its molecular mechanisms, and review the therapeutic strategies and prospects based on the regulation of mitophagy.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719377","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":"Induced Human-like Coronary Stenosis in Hypercholesterolemic PCSK9 Minipigs.","authors":"Jacob Nicolaisen, Christian Frøsig Bo Poulsen, Martin Mæng Bjørklund, Martin Nors Skov, Maiken Kudahl Larsen, Troels Thim, Jouke Dijkstra, Jacob Fog Bentzon, Evald Høj Christiansen, Niels Ramsing Holm","doi":"10.1007/s12265-025-10607-0","DOIUrl":"https://doi.org/10.1007/s12265-025-10607-0","url":null,"abstract":"<p><p>Translational models for obstructive coronary artery disease are lacking. We aimed to develop a porcine model for obstructive coronary stenosis induced by bioresorbable stent (BRS) implantation in hypercholesterolemic proprotein convertase subtilisin/kexin-9 (PCSK9) minipigs. Fifteen hypercholesterolemic PCSK9 minipigs were randomized to percutaneous coronary intervention with Magmaris, Absorb or Desolve BRS. Optical coherence tomography (OCT) scans were performed at baseline and 6-months followed by histology. Matched OCT analysis showed minimal lumen area decreased from 7.62 ± 1.54 mm² at baseline to 2.12 ± 0.92 mm² at follow-up in the Magmaris group, from 6.99 ± 1.49 mm² to 3.07 ± 1.52 mm² in the Absorb group, and from 6.05 ± 1.11 mm² to 2.65 ± 0.93 mm² in the Desolve group. Histologic examination revealed advanced human-like stenosis. BRS implantation in hypercholesterolemic PCSK9 minipigs induced human-like stenoses and may serve as a feasible preclinical model for obstructive coronary artery disease.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709945","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":"Roles of Lipoxygenases in Cardiovascular Diseases.","authors":"Ting Liu, Ding Ai","doi":"10.1007/s12265-025-10605-2","DOIUrl":"https://doi.org/10.1007/s12265-025-10605-2","url":null,"abstract":"<p><p>Lipoxygenases (LOXs) are a family of dioxygenases that catalyze the peroxidation of polyunsaturated fatty acids, such as linoleic acid and arachidonic acid, initiating the synthesis of bioactive lipid mediators. The LOX-mediated production of these bioactive molecules in various cell types plays a critical role in the pathophysiology of cardiovascular diseases, including atherosclerosis, hypertension, and myocardial ischemia-reperfusion injury. In this review, we summarize the roles of LOXs and their products in different cardiovascular cells and conditions, offering valuable insights may contribute to the development of novel therapeutic strategies for cardiovascular diseases.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709947","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 Egr2 Protects against TAC-induced Heart Failure in Mice by Suppressing Inflammation and Apoptosis Via Targeting Acot1 in Cardiomyocytes.","authors":"Xiaolu Hou, Guoling Hu, Heling Wang, Ying Yang, Qi Sun, Xiuping Bai","doi":"10.1007/s12265-025-10602-5","DOIUrl":"https://doi.org/10.1007/s12265-025-10602-5","url":null,"abstract":"<p><p>Heart failure (HF) is a clinical syndrome caused by structural or functional abnormalities in heart. Egr2 has been reported to be protective for multiple diseases, but its effect on HF remains unknown. The present study intended to investigate the potential role of Egr2 in HF and its possible downstream effectors. High Egr2 expression in heart was observed in HF mice. Egr2 knockdown alleviated cardiac damage and function in HF mice. Egr2 knockdown inhibited myocardial inflammation and apoptosis both in vivo and in vitro. Egr2 inhibited Acot1 transcription expression via directly binding to its promoter. Acot1 overexpression reduced Lipopolysaccharide (LPS)-induced cardiomyocyte inflammation and apoptosis. Functional rescue experiments revealed that Acot1 reversed the effects of Egr2 on LPS-induced cell apoptosis and inflammation. Overall, Egr2 knockdown might ameliorate HF by inhibiting inflammation and apoptosis in cardiomyocytes by targeting Acot1. This study might provide evidence to better understand the molecular mechanisms of HF pathogenesis.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648584","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":"PLK1 Downregulation Attenuates ET-1-Induced Cardiomyocyte Hypertrophy by Suppressing the ERK1/2 Pathway.","authors":"Jie Ding, Anqi Yang, Liping Zhou, Fulei Zhang, Huixing Zhou, Yuemei Zhang, Yan Wang, Yi Liu, Dandan Liang, Yuanyuan Liu, Yahan Wu","doi":"10.1007/s12265-025-10604-3","DOIUrl":"https://doi.org/10.1007/s12265-025-10604-3","url":null,"abstract":"<p><p>Cardiomyocyte hypertrophy is a key remodeling response to cardiac stress and an independent risk factor for heart failure. However, the molecular mechanism of cardiomyocyte hypertrophy is not yet fully understood. We here found Polo-like kinase 1 (PLK1) was crucial in regulating endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. Notably, PLK1 expression was significantly elevated in ET-1-induced hypertrophic cardiomyocytes and pressure overload-induced hypertrophic cardiac tissue. Knocking down Plk1 reduced the cell size of hypertrophic cardiomyocytes and suppressed the expression of hypertrophic markers, including ANP, BNP and β-MHC. The PLK1 inhibitor BI2536 had similar effects on hypertrophic cardiomyocytes. Mechanistically, the ERK1/2 pathway was identified as the key downstream pathway mediating the effects of PLK1 on ET-1-induced cardiomyocyte hypertrophy. Finally, the deficiency of PLK1 attenuated the hypertrophy of hiPSC-CMs. In summary, our study revealed that PLK1 regulates ET-1-induced cardiomyocyte hypertrophy through the ERK1/2 pathway, providing insights into the pathogenesis and potential therapies for pathological cardiac hypertrophy.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648585","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":"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}