JACC: Basic to Translational Science最新文献

{"title":"Double-Edged Signaling","authors":"Neha E.H. Dinesh PhD , Dieter P. Reinhardt PhD","doi":"10.1016/j.jacbts.2025.101370","DOIUrl":"10.1016/j.jacbts.2025.101370","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101370"},"PeriodicalIF":8.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Implications of ErbB Pathway Modification in Heart Failure with Reduced Ejection Fraction","authors":"Senthil Selvaraj MD, MS, MA , G. Michael Felker MD, MHS","doi":"10.1016/j.jacbts.2025.101371","DOIUrl":"10.1016/j.jacbts.2025.101371","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101371"},"PeriodicalIF":8.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144879347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma-Derived Extracellular Vesicle-Propagated microRNA From Aortic Stenosis Patients Render Pro-Calcifying Effects on Valve Interstitial Cells","authors":"Avinash B. Khandagale PhD ,&nbsp;Padraic Corcoran PhD ,&nbsp;Yuzhen Dan PhD ,&nbsp;Anders Isaksson PhD ,&nbsp;Stefan James MD, PhD ,&nbsp;Agneta Siegbahn MD, PhD ,&nbsp;Christina Christersson MD, PhD","doi":"10.1016/j.jacbts.2025.101327","DOIUrl":"10.1016/j.jacbts.2025.101327","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) and microRNAs (miRs) have been found to be differently expressed in patients with aortic valve stenosis (AS). Here, we profiled the expression of miRs associated with circulating EVs from severe AS patients and found several altered miRs compared with healthy counterparts. EVs from AS patients induced calcification through expression of the pro-osteogenic genes osteocalcin and osteopontin with corresponding proteins. The expression levels of miR-455-3p and miR-103a-3p were found correlated to the calcification of VICs. Alteration in these miR abrogated osteogenic differentiation of VICs. Additionally, BMP4 and transcriptional factor RUNX2 were found affected by these miRs.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101327"},"PeriodicalIF":8.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144863905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Efficacy of a Hemostatic Agent in Overcoming Dual Antiplatelet Therapy","authors":"Evgeni Efimenko PhD ,&nbsp;Hairu Zhao MS ,&nbsp;Keith Moskowitz PhD ,&nbsp;Conrad Smith MD ,&nbsp;Robert Pyo MD ,&nbsp;Thomas G. Diacovo MD","doi":"10.1016/j.jacbts.2025.101356","DOIUrl":"10.1016/j.jacbts.2025.101356","url":null,"abstract":"<div><div>This preclinical evaluation of a prohemostatic agent involved patients who received aspirin and clopidogrel before coronary artery stenting, the use of a humanized animal model to assess the hemostatic properties of patient platelets, as well as microfluidic assays to measure platelet reactivity. We demonstrate that our investigational product can bypass the effects of dual antiplatelet therapy (DAPT) by generating thrombin at sites of vascular injury, thereby restoring the hemostatic properties of patient platelets. Importantly, its effects could be reversed upon administration of a thrombin inhibitor. Thus, this product offers a titratable and reversible strategy for the management of defective hemostasis associated with DAPT.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101356"},"PeriodicalIF":8.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Systems Biology Identifies Disruptions in Mitochondrial Function and Metabolism as Key Contributors to HFpEF","authors":"Andrew A. Gibb PhD ,&nbsp;Kyle LaPenna MD, PhD ,&nbsp;Ryan B. Gaspar BS ,&nbsp;Nadina R. Latchman BS ,&nbsp;Yinfei Tan PhD ,&nbsp;Carmen Choya-Foces PhD ,&nbsp;Jake E. Doiron PhD ,&nbsp;Zhen Li PhD ,&nbsp;Huijing Xia PhD ,&nbsp;Michael P. Lazaropoulos PhD ,&nbsp;Mariell Conwell BS ,&nbsp;Thomas E. Sharp III PhD ,&nbsp;Traci T. Goodchild PhD ,&nbsp;David J. Lefer PhD ,&nbsp;John W. Elrod PhD","doi":"10.1016/j.jacbts.2025.101334","DOIUrl":"10.1016/j.jacbts.2025.101334","url":null,"abstract":"<div><div>Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. We utilized a systems-biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. Male ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14 weeks of age for extensive physiological phenotyping and left ventricle (LV) tissue harvesting for unbiased-metabolomics, RNA-sequencing, and mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes driving HFpEF pathology, versus hypertension + metabolic syndrome. Comparison of ZSF1-lean vs WKY (ie, hypertension-exclusive effects) revealed metabolic remodeling suggesting increased aerobic glycolysis, decreased β-oxidation, and dysregulated purine and pyrimidine metabolism with few transcriptional changes. ZSF1-obese rats displayed worsened metabolic remodeling and robust transcriptional remodeling highlighted by upregulation of inflammatory genes and downregulation of the mitochondrial structure/function and metabolic processes. Integrated network analysis of metabolomic and RNAseq datasets revealed downregulation of most catabolic energy producing pathways, manifesting in a marked decrease in the energetic state (ie, reduced ATP/ADP, PCr/ATP). Cardiomyocyte ultrastructure analysis revealed decreased mitochondrial area, size, and cristae density, as well as increased lipid droplet content in HFpEF hearts. Impaired mitochondrial function was demonstrated by decreased substrate-mediated respiration and dysregulated calcium handling. Collectively, the integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101334"},"PeriodicalIF":8.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota Transplant Therapy Is Safe and Feasible in Pulmonary Arterial Hypertension","authors":"Daphne Moutsoglou MD, PhD ,&nbsp;Madelyn Blake BS ,&nbsp;Dina C. Belhasan MD ,&nbsp;Gretchen Peichel BAN ,&nbsp;Brenda M. Vang AAS ,&nbsp;E. Kenneth Weir MD ,&nbsp;Sharon Lopez BS ,&nbsp;Kurt W. Prins MD, PhD ,&nbsp;Amanda J. Kabage MS ,&nbsp;Sasha Z. Prisco MD, PhD ,&nbsp;Benjamin P. Kremer BS ,&nbsp;Alexander Khoruts MD, MS ,&nbsp;Thenappan Thenappan MD","doi":"10.1016/j.jacbts.2025.101347","DOIUrl":"10.1016/j.jacbts.2025.101347","url":null,"abstract":"<div><div>Pulmonary arterial hypertension (PAH) is a complex inflammatory disease that the gut microbiome likely contributes to and may be a potential therapeutic avenue for nontoxically improving outcomes. Here, we show that microbiota transplant therapy (MTT) is safe and feasible. The MTT regimen achieves only modest levels of donor microbiota engraftment but is accompanied by a transient reduction in circulating pro-inflammatory cytokines. These findings of decreased systemic inflammation with only modest donor engraftment support the potential of MTT as a novel treatment for PAH. (Microbiota Transplant Therapy for Pulmonary Arterial Hypertension: Early Safety and Feasibility Study; <span><span>NCT04884971</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101347"},"PeriodicalIF":8.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cracking the Code of a Preclinical Rodent Model of HFpEF","authors":"Chae-Myeong Ha PhD,&nbsp;Adam R. Wende PhD","doi":"10.1016/j.jacbts.2025.101357","DOIUrl":"10.1016/j.jacbts.2025.101357","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101357"},"PeriodicalIF":8.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primed to Fail","authors":"Harvey G. Roweth PhD","doi":"10.1016/j.jacbts.2025.101358","DOIUrl":"10.1016/j.jacbts.2025.101358","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101358"},"PeriodicalIF":8.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired Secondary Platelet Response in Chronic Kidney Disease as a Consequence of Prior Platelet Activation","authors":"Constance C.F.M.J. Baaten PhD ,&nbsp;Julia Wollenhaupt PhD ,&nbsp;Tobias M. Henning MD ,&nbsp;Sonja Vondenhoff MS ,&nbsp;Jonas R. Schröer MD ,&nbsp;Eleni Stamellou MD, PhD, MS ,&nbsp;Turgay Saritas MD, PhD ,&nbsp;Berkan Kurt MD ,&nbsp;Leonard Boger MD ,&nbsp;Alessandra Antwerpen ,&nbsp;Juliane Hermann PhD ,&nbsp;Magdolna Nagy PhD ,&nbsp;Marieke Sternkopf PhD ,&nbsp;Eva Miriam Buhl PhD ,&nbsp;Ute Raffetseder PhD ,&nbsp;Paola E.J. van der Meijden PhD ,&nbsp;Marijke J.E. Kuijpers PhD ,&nbsp;Henri M.H. Spronk PhD ,&nbsp;Stefan J. Schunk MD ,&nbsp;Joachim Jankowski PhD ,&nbsp;Heidi Noels PhD","doi":"10.1016/j.jacbts.2025.101355","DOIUrl":"10.1016/j.jacbts.2025.101355","url":null,"abstract":"<div><div>Patients with chronic kidney disease (CKD) are at increased risk of thrombotic and hemorrhagic complications. Findings on platelet defects in CKD are conflicting. Therefore, we examined platelet function in CKD stage 3 to 5 dialysis patients without antithrombotic therapy, in CKD5D/hemodialysis patients on acetylsalicylic acid (ASA) as well as in a CKD mouse model. Patients with advanced CKD without antithrombotic therapy show platelet preactivation with a partial secondary platelet dysfunction mainly upon collagen/GPVI stimulation. Platelets from hemodialysis patients on ASA showed a less severe CKD-associated secondary platelet dysfunction compared with those not taking ASA, with comparable observations in CKD mice on ASA vs vehicle.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101355"},"PeriodicalIF":8.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focal Adhesion Kinase Drives Rho/ROCK and mTOR Signaling to Protect and Augment Aortic Dissections","authors":"Zhen Zhou MD ,&nbsp;Pujun Guan PhD ,&nbsp;Ripon Sarkar PhD ,&nbsp;Yang Yu MD ,&nbsp;Alexis Richard PhD ,&nbsp;Dar Weiss PhD ,&nbsp;Yuki Kawamura PhD ,&nbsp;Chen Zhang MD ,&nbsp;Yanming Li PhD ,&nbsp;Tomas Vaisar PhD ,&nbsp;Daniel R. Martin PhD ,&nbsp;L. Maximillian Buja MD ,&nbsp;Zhouxuan Li PhD ,&nbsp;Kartik Venkatachalam PhD ,&nbsp;Ying H. Shen MD, PhD ,&nbsp;Scott A. LeMaire MD ,&nbsp;Jay D. Humphrey PhD ,&nbsp;Dianna M. Milewicz MD, PhD","doi":"10.1016/j.jacbts.2025.101353","DOIUrl":"10.1016/j.jacbts.2025.101353","url":null,"abstract":"<div><div>Dysfunctional mechanosensing via focal adhesions (FAs) significantly contributes to thoracic aortic dissection in the β-aminopropionitrile mouse model by triggering FA kinase activation and subsequent Rho/ROCK and mTOR signaling pathways. The present findings indicate that these signaling pathways play distinct roles in ascending vs descending dissections. Specifically, in the ascending aorta, smooth muscle cell FA kinase–Rho/ROCK signaling acts as a beneficial adaptive mechanism to prevent dissections, whereas mTOR signaling is pathogenic and contributes to dissections.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 9","pages":"Article 101353"},"PeriodicalIF":8.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}