{"title":"Mesenchymal Stem Cell-Derived Exosomes and Their MicroRNAs in Heart Repair and Regeneration.","authors":"Nukhba Akbar, Syeda Saima Razzaq, Asmat Salim, Kanwal Haneef","doi":"10.1007/s12265-023-10449-8","DOIUrl":"10.1007/s12265-023-10449-8","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) can be differentiated into cardiac, endothelial, and smooth muscle cells. Therefore, MSC-based therapeutic approaches have the potential to deal with the aftermaths of cardiac diseases. However, transplanted stem cells rarely survive in damaged myocardium, proposing that paracrine factors other than trans-differentiation may involve in heart regeneration. Apart from cytokines/growth factors, MSCs secret small, single-membrane organelles named exosomes. The MSC-secreted exosomes are enriched in lipids, proteins, nucleic acids, and microRNA (miRNA). There has been an increasing amount of data that confirmed that MSC-derived exosomes and their active molecule microRNA (miRNAs) regulate signaling pathways involved in heart repair/regeneration. In this review, we systematically present an overview of MSCs, their cardiac differentiation, and the role of MSC-derived exosomes and exosomal miRNAs in heart regeneration. In addition, biological functions regulated by MSC-derived exosomes and exosomal-derived miRNAs in the process of heart regeneration are reviewed.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"505-522"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158040","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}
Glisant Plasa, Elizabeth Hillier, Judy Luu, Dominic Boutet, Mitchel Benovoy, Matthias G Friedrich
{"title":"Automated Data Transformation and Feature Extraction for Oxygenation-Sensitive Cardiovascular Magnetic Resonance Images.","authors":"Glisant Plasa, Elizabeth Hillier, Judy Luu, Dominic Boutet, Mitchel Benovoy, Matthias G Friedrich","doi":"10.1007/s12265-023-10474-7","DOIUrl":"10.1007/s12265-023-10474-7","url":null,"abstract":"<p><p>Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) is a novel, powerful tool for assessing coronary function in vivo. The data extraction and analysis however are labor-intensive. The objective of this study was to provide an automated approach for the extraction, visualization, and biomarker selection of OS-CMR images. We created a Python-based tool to automate extraction and export of raw patient data, featuring 3336 attributes per participant, into a template compatible with common data analytics frameworks, including the functionality to select predictive features for the given disease state. Each analysis was completed in about 2 min. The features selected by both ANOVA and MIC significantly outperformed (p < 0.001) the null set and complete set of features in two datasets, with mean AUROC scores of 0.89eatures f 0.94lete set of features in two datasets, with mean AUROC scores that our tool is suitable for automated data extraction and analysis of OS-CMR images.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"705-715"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478546","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}
Jing Zhang, Wen-Qian Huang, Yu-Rong Zhang, Na Liang, Nan-Ping Li, Gang-Kai Tan, Shao-Xin Gong, Ai-Ping Wang
{"title":"Upregulation of eIF2α by m<sup>6</sup>A modification accelerates the proliferation of pulmonary artery smooth muscle cells in MCT-induced pulmonary arterial hypertension rats.","authors":"Jing Zhang, Wen-Qian Huang, Yu-Rong Zhang, Na Liang, Nan-Ping Li, Gang-Kai Tan, Shao-Xin Gong, Ai-Ping Wang","doi":"10.1007/s12265-023-10458-7","DOIUrl":"10.1007/s12265-023-10458-7","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a malignant cardiovascular disease. Eukaryotic initiation factor 2α (eIF2α) plays an important role in the proliferation of pulmonary artery smooth muscle cells (PASMCs) in hypoxia-induced pulmonary hypertension (HPH) rats. However, the regulatory mechanism of eIF2α remains poorly understood in PAH rats. Here, we discover eIF2α is markedly upregulated in monocrotaline (MCT)-induced PAH rats, eIF2α can be upregulated by mRNA methylation, and upregulated eIF2α can promote PASMC proliferation in MCT-PAH rats. GSK2606414, eIF2α inhibitor, can downregulate the expression of eIF2α and alleviate PASMC proliferation in MCT-PAH rats. And we further discover the mRNA of eIF2α has a common sequence with N 6-methyladenosine (m<sup>6</sup>A) modification by bioinformatics analysis, and the expression of METTL3, WTAP, and YTHDF1 is upregulated in MCT-PAH rats. These findings suggest a potentially novel mechanism by which eIF2α is upregulated by m<sup>6</sup>A modification in MCT-PAH rats, which is involved in the pathogenesis of PAH.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"598-608"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136397571","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}
Si Chen, Zhan Li, Haolong Li, Xiaoli Zeng, Hui Yuan, Yongzhe Li
{"title":"RNA Sequencing of Whole Blood in Premature Coronary Artery Disease: Identification of Novel Biomarkers and Involvement of T Cell Imbalance.","authors":"Si Chen, Zhan Li, Haolong Li, Xiaoli Zeng, Hui Yuan, Yongzhe Li","doi":"10.1007/s12265-023-10465-8","DOIUrl":"10.1007/s12265-023-10465-8","url":null,"abstract":"<p><p>Serum biomarkers were explored based on the peripheral blood gene expression profiles of premature coronary artery disease (PCAD). RNA sequencing (RNA-Seq) was used to detect PCAD-specific differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (RT-PCR) was used to validate the most significant DEGs, and enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the effect on corresponding serum proteins. Fifty-nine PCAD-specific DEGs were identified. Functional analysis showed positive regulation of T cell-mediated cytotoxicity, regulation of T cell-mediated immunity, and the regulation of alpha-beta T cell proliferation which were enriched in PCAD. RT-PCR validated the significant difference in the expression of BAG6, MUC5B, and APOA2 between PCAD and late-onset coronary artery disease (LCAD) patients. ELISA validation showed serum MUC5B increased dramatically in PCAD when compared to LCAD. Our study found T cells contribute to the occurrence of PCAD, and the inflammatory factor MUC5B may be a novel serum marker in PCAD patients.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"638-647"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460125","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}
Bin Jiang, Xinlong Wang, Nancy Rivera-Bolanos, Guillermo A Ameer
{"title":"Generation of Autologous Vascular Endothelial Cells for Patients with Peripheral Artery Disease.","authors":"Bin Jiang, Xinlong Wang, Nancy Rivera-Bolanos, Guillermo A Ameer","doi":"10.1007/s12265-023-10452-z","DOIUrl":"10.1007/s12265-023-10452-z","url":null,"abstract":"<p><p>Peripheral artery disease (PAD) is a prevalent cardiovascular disease with risks of limb loss. Our objective is to establish an autologous cell source for vascular regeneration to achieve limb salvage in PAD. Six PAD patients (age 50-80) were enrolled with their peripheral blood collected to derive vascular endothelial cells (ECs) with two different approaches: (1) endothelial progenitor cell (EPC) approach and (2) induced pluripotent stem cell (iPSC) approach. The iPSC approach successfully generated patient-specific ECs for all PAD patients, while the EPC approach did not yield any colony-forming ECs in any of the patients. The patient-derived iPSC-ECs expressed endothelial markers and exhibited endothelial functions. However, elevated inflammatory status with VCAM-1 expression was observed in the patient-derived cells. Pharmacological treatment with resveratrol resulted in patient-specific responses in cell viability and VCAM-1 expression. Our study demonstrates the potential of iPSC-ECs for autologous regenerative therapy in PAD, offering promise for personalized treatments for ischemic PAD.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"558-569"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677857","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}
Zhi Du, Kai Wang, Yawei Cui, Xudong Xie, Ruoyu Zhu, Fanghong Dong, Xiaogang Guo
{"title":"The China Hypertrophic Cardiomyopathy Project (CHCMP): The Rationale and Design of a Multicenter, Prospective, Registry Cohort Study.","authors":"Zhi Du, Kai Wang, Yawei Cui, Xudong Xie, Ruoyu Zhu, Fanghong Dong, Xiaogang Guo","doi":"10.1007/s12265-023-10477-4","DOIUrl":"10.1007/s12265-023-10477-4","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is associated with adverse outcomes, such as heart failure, arrhythmia, and mortality. Sudden cardiac death (SCD) is a common cause of death in HCM patients, and identification of patients at a high risk of SCD is crucial in clinical practice. The China Hypertrophic Cardiomyopathy Project is a hospital-based, multicenter, prospective, registry cohort study of HCM patients, covering a total of 3000 participants and with a 5-year follow-up plan. A large number of demographic characteristics and clinical data will be fully collected to identify prognostic factors in Chinese HCM patients. Furthermore, the main purpose of this study is to integrate demographic and clinical characteristics to establish new 5-year SCD risk predictive equations for Chinese HCM patients by the use of machine learning technologies. The project has crucial clinical significance for risk stratification and determination of HCM patients with high risk of adverse outcomes. CLINICAL TRIALS REGISTRATION: ChiCTR2300070909.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"732-738"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097932","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":"Role of Flow-Sensitive Endothelial Genes in Atherosclerosis and Antiatherogenic Therapeutics Development.","authors":"Kyung In Baek, Kitae Ryu","doi":"10.1007/s12265-023-10463-w","DOIUrl":"10.1007/s12265-023-10463-w","url":null,"abstract":"<p><p>Atherosclerosis is a chronic inflammatory disease that is the underlying cause of cardiovascular disease which initiates from endothelial dysfunction from genetic and environmental risk factors, including biomechanical forces: blood flow. Endothelial cells (ECs) lining the inner arterial wall regions exposed to disturbed flow are prone to atherosclerosis development, whereas the straight regions exposed to stable flow are spared from the disease. These flow patterns induce genome- and epigenome-wide changes in gene expression in ECs. Through the sweeping changes in gene expression, disturbed flow reprograms ECs from athero-protected cell types under the stable flow condition to pro-atherogenic cell conditions. The pro-atherogenic changes induced by disturbed flow, in combination with additional risk factors such as hypercholesterolemia, lead to the progression of atherosclerosis. The flow-sensitive genes and proteins are critical in understanding the mechanisms and serve as novel targets for antiatherogenic therapeutics.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"609-623"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444802","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":"Genetically Proxied Therapeutic Effect of Metformin Use, Blood Pressure, and Hypertension's Risk: a Drug Target-Based Mendelian Randomization Study.","authors":"Junhong Jiang, Di Hu, Qi Zhang, Zenan Lin","doi":"10.1007/s12265-023-10460-z","DOIUrl":"10.1007/s12265-023-10460-z","url":null,"abstract":"<p><p>In this work, we aim to evaluate the association of the genetically proxied effect of metformin on blood pressure (BP) and hypertension through a drug target-based Mendelian randomization (MR) analysis. Thirty-two instrumental variables for five metformin targets (i.e., AMP-activated protein kinase (AMPK), growth differentiation factor 15 (GDF15), mitochondrial glycerol 3 (MG3), mitochondrial complex I (MCI), and glucagon (GCG)) were introduced to the MR analysis on the datasets of hypertension, systolic and diastolic blood pressure (SBP and DBP). The MR analyses demonstrated that the MCI- and MG3-specific metformin's use would significantly reduce SBP, DBP, and hypertension risk. The meta-analyses showed that the genetically proxied metformin's use equivalent to a 6.75 mmol/mol reduction on HbA1c could decrease both the SBP (beta = - 1.05, P < 0.001) and DBP (beta = - 0.51, P = 0.096). Furthermore, metformin's use was also implied to reduce the hypertension risk. The MG3- and MCI-dependent metformin's effect may play key roles in the anti-hypertension function.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"716-722"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138444800","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}
Yangyang Jiang, Shuchao Pang, Xiaoyu Liu, Lixin Wang, Yi Liu
{"title":"The Gut Microbiome Affects Atherosclerosis by Regulating Reverse Cholesterol Transport.","authors":"Yangyang Jiang, Shuchao Pang, Xiaoyu Liu, Lixin Wang, Yi Liu","doi":"10.1007/s12265-024-10480-3","DOIUrl":"10.1007/s12265-024-10480-3","url":null,"abstract":"<p><p>The human system's secret organ, the gut microbiome, has received considerable attention. Emerging research has yielded substantial scientific evidence indicating that changes in gut microbial composition and microbial metabolites may contribute to the development of atherosclerotic cardiovascular disease. The burden of cardiovascular disease on healthcare systems is exacerbated by atherosclerotic cardiovascular disease, which continues to be the leading cause of mortality globally. Reverse cholesterol transport is a powerful protective mechanism that effectively prevents excessive accumulation of cholesterol for atherosclerotic cardiovascular disease. It has been revealed how the gut microbiota modulates reverse cholesterol transport in patients with atherosclerotic risk. In this review, we highlight the complex interactions between microbes, their metabolites, and their potential impacts in reverse cholesterol transport. We also explore the feasibility of modulating gut microbes and metabolites to facilitate reverse cholesterol transport as a novel therapy for atherosclerosis.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"624-637"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478561","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}
Xiaorong Jian, Dehua Yang, Li Wang, Hongxiang Wang
{"title":"CREB1 Silencing Protects Against Inflammatory Response in Rats with Deep Vein Thrombosis Through Reducing RPL9 Expression and Blocking NF-κB Signaling.","authors":"Xiaorong Jian, Dehua Yang, Li Wang, Hongxiang Wang","doi":"10.1007/s12265-023-10450-1","DOIUrl":"10.1007/s12265-023-10450-1","url":null,"abstract":"<p><p>Apoptosis and inflammation of vascular endothelial cells (VECs) are the most important causes of deep vein thrombosis (DVT). cAMP response element binding protein 1 (CREB1) encodes a transcription factor that binds as a homodimer to the cAMP-responsive element and can promote inflammation. CREB1 is found to be upregulated in the plasma of patients with venous thromboembolism. However, the biological functions of CREB1 in DVT remain unknown. We evaluated the effect of CREB1 in a rat model of inferior vena cava (IVA) stenosis-induced DVT. IVC stenosis resulted in stable thrombus, inflammatory response and CREB1 upregulation, whereas CREB1 knockdown inhibited thrombus and inflammation in DVT rats. In vitro analysis showed that CREB1 knockdown inhibited VEC apoptosis. Mechanistically, CREB1 knockdown reduced Ribosomal protein L9 (RPL9) expression and blocked the NF-κB pathway. Therefore, CREB1 may become a potential therapeutic target of DVT prevention.</p>","PeriodicalId":15224,"journal":{"name":"Journal of Cardiovascular Translational Research","volume":" ","pages":"570-584"},"PeriodicalIF":4.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61562814","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}