{"title":"Targeting Canonical Wnt-signaling Through GSK-3β in Arrhythmogenic Cardiomyopathy: Conservative or Progressive?","authors":"Brandon Shu Huang Low, Angeliki Asimaki","doi":"10.1007/s12265-024-10567-x","DOIUrl":"10.1007/s12265-024-10567-x","url":null,"abstract":"<p><p>Arrhythmogenic cardiomyopathy is a primary myocardial disease and a major cause of sudden death in all populations of the world. Canonical Wnt signalling is a critical pathway controlling numerous processes including cellular differentiation, hypertrophy and development. GSK3β is a ubiquitous serine/threonine kinase, which acts downstream of Wnt to promote protein ubiquitination and proteasomal degradation. Several studies now suggest that inhibiting GSK3β can prevent and reverse key pathognomonic features of ACM in a range of experimental models. However, varying concerns are reported throughout the literature including the risk of paradoxical arrhythmias, cancer and off-target effects in upstream or downstream pathways. CLINICAL RELEVANCE: In light of the start of the phase 2 TaRGET clinical trial, designed to evaluate the potential therapeutic efficacy of GSK3β inhibition in patients with arrhythmogenic cardiomyopathy, this report aims to review the advantages and disadvantages of this strategy.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"121-132"},"PeriodicalIF":2.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400330","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":"Long Non-Coding RNAs in Diabetic Cardiomyopathy: Potential Function as Biomarkers and Therapeutic Targets of Exercise Training.","authors":"Jie Hu, Xinwen Miao, Li-Hua Yu","doi":"10.1007/s12265-024-10586-8","DOIUrl":"https://doi.org/10.1007/s12265-024-10586-8","url":null,"abstract":"<p><p>Recent studies emphasize the beneficial effects of exercise on diabetic cardiomyopathy (DCM), adding to the growing body of evidence that underscores the role of exercise in improving health outcomes. Despite this, a notable gap persists in the number of healthcare providers who actively prescribe exercise as a therapeutic intervention for DCM management. In addition, exercise modulates the expression of lncRNAs, which play a pivotal role in DCM progression. Further investigation into this relationship may facilitate the identification of novel biomarkers and therapeutic targets for DCM. This review consolidates recent advances in identifying lncRNAs biomarkers in DCM, summarizing the current knowledge on dysregulated lncRNAs and their molecular mechanisms. Additionally, it offers new insights into the mechanistic roles of lncRNAs, highlighting their potential as biomarkers and therapeutic targets for DCM. Overall, this review aims to inform future research and reinforce the significance of addressing diabetes-related cardiovascular diseases to potentially improve clinical outcomes.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949529","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":"Gut Microbiota as Predictive Biomarker for Chronic Heart Failure in Patients with Different Nutritional Risk.","authors":"Chen Yang, Xiaopeng Li, Miaomiao Hu, Ting Li, Li Jiang, Yong Zhang","doi":"10.1007/s12265-024-10529-3","DOIUrl":"10.1007/s12265-024-10529-3","url":null,"abstract":"<p><p>To examine the relationship between gut microbiota and disease development in chronic heart failure patients with different nutritional risk. The study analyzed stool samples from 62 CHF patients and 21 healthy peoples using 16S rRNA gene sequencing. CHF patients were separated into risk (n = 30) and non-risk group (n = 32) based on NRS2002 scores. Analysis methods used were LEfSe, random forest regression model, ROC curves, BugBase, PICRUSt2, metagenomeSeq. Risk group includes 11 cases of HFrEF, 6 cases of HFpEF, and 13 cases of HFmrEF. LefSe analysis confirmed that the risk group had higher levels of Enterobacter and Escherichia-Shigella. Correlation analysis revealed a negative correlation between prealbumin and Escherichia-Shigella. The presence of Enterobacter and Escherichia-Shigella worsens intestinal inflammation in CHF patients, impacting lysine metabolism by influencing its degradation metabolic function. This interference further disrupts albumin and prealbumin synthesis, leading to malnutrition in CHF patients and ultimately worsening the disease.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1240-1257"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442761","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}
Michiaki Nagai, Keigo Dote, Masaya Kato, Shota Sasaki, Noboru Oda, Sunny S Po, Tarun W Dasari
{"title":"Blood Pressure Variability After Non-invasive Low-level Tragus Stimulation in Acute Heart Failure.","authors":"Michiaki Nagai, Keigo Dote, Masaya Kato, Shota Sasaki, Noboru Oda, Sunny S Po, Tarun W Dasari","doi":"10.1007/s12265-024-10544-4","DOIUrl":"10.1007/s12265-024-10544-4","url":null,"abstract":"<p><p>Higher blood pressure (BP) variability (BPV) was shown to be strong predictors of poor cardiovascular outcomes in heart failure (HF). It is currently unknown if low-level tragus stimulation (LLTS) would lead to improvement in BPV in acute HF (AHF). The 22 patients with AHF (median 80 yrs, males 60%) were randomly assigned to active or sham group using an ear clip attached to the tragus (active group) or the earlobe (sham group) for 1 h daily over 5 days. In the active group, standard deviation (SD), coefficient of variation (CV) and δ in SBP were significantly decreased after LLTS (all p < 0.05). All the changes in SD, CV and δ in SBP before and after stimulation were also significantly different between active and sham groups (all p < 0.05). This proof-of-concept study demonstrates the beneficial effects of LLTS on BPV in AHF.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1347-1352"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537953","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":"HnRNPA1 Prevents Endothelial-to-mesenchymal Transition-induced VSMC Activation and Neointimal Hyperplasia in Vein Grafts.","authors":"Haoliang Liu, Chaoqun Wang, Rui Wang, Yi Zhang, Bohao Jian, Zhuoming Zhou, Zhongkai Wu, Mengya Liang","doi":"10.1007/s12265-024-10545-3","DOIUrl":"10.1007/s12265-024-10545-3","url":null,"abstract":"<p><p>Endothelial-to-mesenchymal transition (EndoMT) is associated with neointimal hyperplasia and vein graft failure, and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has emerged as a major modulator of EMT. We aimed to investigate the functional consequence of EndoMT in neointimal hyperplasia and the precise role of hnRNPA1 in the regulation of EndoMT and neointimal hyperplasia. We investigated the spatial and temporal distribution characteristics of EndoMT cells in a mouse model of vein graft transplantation. In vitro, we studied the interaction between EndoMT cells and VSMCs, and the underlying mechanism was investigated by cytokine antibody assays. In cultured HUVECs, we studied the effect of hnRNPA1 on EndoMT and the cellular interactions by using siRNA-mediated knockdown and adenovirus-mediated overexpression. We further investigated the role of hnRNPA1 in EndoMT and neointimal hyperplasia in vivo with an AAV-mediated EC-specific hnRNPA1 overexpression murine model. We demonstrated the presence of EndoMT cells during the initial stage of neointimal formation, and that EndoMT cells promoted the proliferation and migration of VSMCs in vitro. Mechanistic studies revealed that EndoMT cells express and secrete a higher level of PDGF-B. Furthermore, we found a regulatory role for hnRNPA1 in EndoMT in vitro and in vivo. Similarly, we found that hnRNPA1 overexpression in ECs reduced the expression and secretion of PDGF-B during EndoMT, effectively inhibiting EndoMT cell-mediated activation of VSMCs in vitro and neointimal formation in vivo. Taken together, these findings indicate that EndoMT cells can activate VSMCs through a paracrine mechanism mediated by hnRNPA1 and lead to neointimal hyperplasia.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1400-1414"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751758","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}
Lorenzo Fassina, Francesco Paolo Lo Muzio, Leonhard Berboth, Jens Ötvös, Alessandro Faragli, Alessio Alogna
{"title":"Prediction of Left Ventricle Pressure Indices Via a Machine Learning Approach Combining ECG, Pulse Oximetry, and Cardiac Sounds: a Preclinical Feasibility Study.","authors":"Lorenzo Fassina, Francesco Paolo Lo Muzio, Leonhard Berboth, Jens Ötvös, Alessandro Faragli, Alessio Alogna","doi":"10.1007/s12265-024-10546-2","DOIUrl":"10.1007/s12265-024-10546-2","url":null,"abstract":"<p><p>Heart failure (HF) is defined as the inability of the heart to meet body oxygen demand requiring an elevation in left ventricular filling pressures (LVP) to compensate. LVP increase can be assessed in the cardiac catheterization laboratory, but this procedure is invasive and time-consuming to the extent that physicians rather rely on non-invasive diagnostic tools. In this work, we assess the feasibility to develop a novel machine-learning (ML) approach to predict clinically relevant LVP indices. Synchronized invasive (pressure-volume tracings) and non-invasive signals (ECG, pulse oximetry, and cardiac sounds) were collected from anesthetized, closed-chest Göttingen minipigs. Animals were either healthy or had HF with reduced ejection fraction and circa 500 heartbeats were included in the analysis for each animal. The ML algorithm showed excellent prediction of LVP indices estimating, for instance, the end-diastolic pressure with a R<sup>2</sup> of 0.955. This novel ML algorithm could assist clinicians in the care of HF patients.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1307-1315"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626848","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}
Ning Zhang, Liangju Liu, Xiaowang Lv, Yixuan Wang, Wei Zhang, Xin Wen, Fan Yu, Tingting Zhou
{"title":"TMAO Impairs Mouse Aortic Vasodilation by Inhibiting TRPV4 Channels in Endothelial Cells.","authors":"Ning Zhang, Liangju Liu, Xiaowang Lv, Yixuan Wang, Wei Zhang, Xin Wen, Fan Yu, Tingting Zhou","doi":"10.1007/s12265-024-10543-5","DOIUrl":"10.1007/s12265-024-10543-5","url":null,"abstract":"<p><p>Trimethylamine oxide (TMAO) is an intestinal flora metabolite associated with risk of cardiovascular diseases. Transient receptor potential vanilloid 4 (TRPV4) is a Ca<sup>2+</sup>-permeable ion channel that is essential for vasodilation and endothelial function. Currently, there are few studies on the effect of TMAO on TRPV4 channels. In the present study, Ca<sup>2+</sup> imaging of vascular tissue showed that TMAO inhibited TRPV4-mediated Ca<sup>2+</sup> influx into aortic endothelial cells in a dose-dependent manner. Furthermore, a whole-cell patch clamp assay showed that TMAO blocked TRPV4-mediated cation currents. Notably, results of aortic vascular tension measurement showed that TMAO impaired endothelium-dependent vasodilation in mouse aortic vessels through the TRPV4-NO pathway. Our results indicated that TMAO inhibited Ca<sup>2+</sup> entry in endothelial cells and impaired vasodilation through the TRPV4-NO pathway in mice. These results provide scientific evidence for novel pathogenic mechanisms underlying the role of TMAO in cardiovascular disease.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1415-1426"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558846","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":"Cirbp: A Key Regulator in Hypothermic Cardioprotection of Aged Donor Hearts During Transplantation.","authors":"Danni Meng, Michail Spanos, Junjie Xiao","doi":"10.1007/s12265-024-10536-4","DOIUrl":"10.1007/s12265-024-10536-4","url":null,"abstract":"","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1466-1467"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620080","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 Kernel Attention-based Transformer Model for Survival Prediction of Heart Disease Patients.","authors":"Palak Kaushal, Shailendra Singh, Rajesh Vijayvergiya","doi":"10.1007/s12265-024-10537-3","DOIUrl":"10.1007/s12265-024-10537-3","url":null,"abstract":"<p><p>Survival analysis is employed to scrutinize time-to-event data, with emphasis on comprehending the duration until the occurrence of a specific event. In this article, we introduce two novel survival prediction models: CosAttnSurv and CosAttnSurv <math><mo>+</mo></math> DyACT. CosAttnSurv model leverages transformer-based architecture and a softmax-free kernel attention mechanism for survival prediction. Our second model, CosAttnSurv <math><mo>+</mo></math> DyACT, enhances CosAttnSurv with Dynamic Adaptive Computation Time (DyACT) control, optimizing computation efficiency. The proposed models are validated using two public clinical datasets related to heart disease patients. When compared to other state-of-the-art models, our models demonstrated an enhanced discriminative and calibration performance. Furthermore, in comparison to other transformer architecture-based models, our proposed models demonstrate comparable performance while exhibiting significant reduction in both time and memory requirements. Overall, our models offer significant advancements in the field of survival analysis and emphasize the importance of computationally effective time-based predictions, with promising implications for medical decision-making and patient care.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"1295-1306"},"PeriodicalIF":2.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893423","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}