JACC: Basic to Translational Science最新文献

{"title":"Association Between Clonal Hematopoiesis and Left Ventricular Reverse Remodeling in Nonischemic Dilated Cardiomyopathy","authors":"","doi":"10.1016/j.jacbts.2024.04.010","DOIUrl":"10.1016/j.jacbts.2024.04.010","url":null,"abstract":"<div><p>Although clonal hematopoiesis of indeterminate potential (CHIP) is an adverse prognostic factor for atherosclerotic disease, its impact on nonischemic dilated cardiomyopathy (DCM) is elusive. The authors performed whole-exome sequencing and deep target sequencing among 198 patients with DCM and detected germline mutations in cardiomyopathy-related genes and somatic mutations in CHIP driver genes. Twenty-five CHIP driver mutations were detected in 22 patients with DCM. Ninety-two patients had cardiomyopathy-related pathogenic mutations. Multivariable analysis revealed that CHIP was an independent risk factor of left ventricular reverse remodeling, irrespective of known prognostic factors. CHIP exacerbated cardiac systolic dysfunction and fibrosis in a DCM murine model. The identification of germline and somatic mutations in patients with DCM predicts clinical prognosis.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 8","pages":"Pages 956-967"},"PeriodicalIF":8.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001839/pdfft?md5=cc874762764de0cd7d19f08b5f3343e6&pid=1-s2.0-S2452302X24001839-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141408407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes","authors":"Paul C. Dimayuga PhD ,&nbsp;Kuang-Yuh Chyu MD, PhD ,&nbsp;Xiaoning Zhao PhD ,&nbsp;Jianchang Zhou PhD ,&nbsp;Nicole Wai Man Lio BS ,&nbsp;Fernando Chernomordik MD ,&nbsp;Daniel Berman MD ,&nbsp;Prediman K. Shah MD ,&nbsp;Bojan Cercek MD, PhD","doi":"10.1016/j.jacbts.2024.04.012","DOIUrl":"10.1016/j.jacbts.2024.04.012","url":null,"abstract":"<div><p>The cathelicidin antimicrobial peptide LL-37 is a self-antigen in neutrophil extracellular traps that provokes autoantibody responses in autoimmune/autoinflammatory conditions. LL-37 immunoglobulin (Ig) G autoantibody levels were measured in subjects with and without atherosclerotic cardiovascular disease assessed using the coronary artery calcium score, in patients who had a future myocardial infarction and in a cohort of acute coronary syndrome (ACS) patients. LL-37 IgG levels were not associated with coronary artery calcium score, but future myocardial infarction patients had significantly higher LL-37 IgG at baseline. Reduced LL-37 IgG in ACS was associated with increased LL-37 IgG–immune complex. ACS plasma increased activated CD62P+ platelets from healthy donors mediated in part by LL-37 IgG–immune complexes and platelet Fc gamma receptor 2a.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 877-887"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24001852/pdfft?md5=a6e5c6a86e9151e8b8e985941cfea515&pid=1-s2.0-S2452302X24001852-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Aortic Stenotic Valve-Derived Extracellular Vesicles Induce Endothelial Dysfunction and Thrombogenicity Through AT1R/NADPH Oxidases/SGLT2 Pro-Oxidant Pathway","authors":"Sandy Hmadeh PhD ,&nbsp;Antonin Trimaille MD, MSc ,&nbsp;Kensuke Matsushita MD, PhD ,&nbsp;Benjamin Marchandot MD ,&nbsp;Adrien Carmona MD ,&nbsp;Fatiha Zobairi BSc ,&nbsp;Chisato Sato MD, PhD ,&nbsp;Michel Kindo MD, PhD ,&nbsp;Tam Minh Hoang MD ,&nbsp;Florence Toti PhD ,&nbsp;Kazem Zibara PhD ,&nbsp;Eva Hamade PhD ,&nbsp;Valérie Schini-Kerth PhD ,&nbsp;Gilles Kauffenstein PhD ,&nbsp;Olivier Morel MD, PhD","doi":"10.1016/j.jacbts.2024.02.012","DOIUrl":"10.1016/j.jacbts.2024.02.012","url":null,"abstract":"<div><p>Pathological tissues release a variety of factors, including extracellular vesicles (EVs) shed by activated or apoptotic cells. EVs trapped within the native pathological valves may act as key mediators of valve thrombosis. Human aortic stenosis EVs promote activation of valvular endothelial cells, leading to endothelial dysfunction, and proadhesive and procoagulant responses.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 845-864"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000901/pdfft?md5=01e109e05e1c49392f43b2d6319c6c96&pid=1-s2.0-S2452302X24000901-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141614402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LL-37: A Direct Link Between Inflammation and Myocardial Infarction","authors":"David J. Schneider MD","doi":"10.1016/j.jacbts.2024.05.007","DOIUrl":"10.1016/j.jacbts.2024.05.007","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 888-889"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002146/pdfft?md5=97f15ae5ef87c5e122e74a9ea0adffe1&pid=1-s2.0-S2452302X24002146-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression","authors":"","doi":"10.1016/j.jacbts.2024.04.006","DOIUrl":"10.1016/j.jacbts.2024.04.006","url":null,"abstract":"<div><p>The serotonin pathway has long been proposed as a promising target for pulmonary arterial hypertension (PAH)—a progressive and uncurable disease. We developed a highly specific inhibitor of the serotonin synthesizing enzyme tryptophan hydroxylase 1 (TPH1), TPT-001 (TPHi). In this study, the authors sought to treat severe PAH in the Sugen/hypoxia (SuHx) rat model with the oral TPHi TPT-001. Male Sprague Dawley rats were divided into 3 groups: 1) ConNx, control animals; 2) SuHx, injected subcutaneously with SU5416 and exposed to chronic hypoxia for 3 weeks, followed by 6 weeks in room air; and 3) SuHx+TPHi, SuHx animals treated orally with TPHi for 5 weeks. Closed-chest right- and left heart catheterization and echocardiography were performed. Lungs were subject to histologic and mRNA sequencing analyses. Compared with SuHx-exposed rats, which developed severe PAH and right ventricular (RV) dysfunction, TPHi-treated SuHx rats had greatly lowered RV systolic (mean ± SEM: 41 ± 2.3 mm Hg vs 86 ± 6.5 mm Hg; <em>P</em> &lt; 0.001) and end-diastolic (mean ± SEM: 4 ± 0.7 mm Hg vs 14 ± 1.7 mm Hg; <em>P</em> &lt; 0.001) pressures, decreased RV hypertrophy and dilation (all not significantly different from control rats), and reversed pulmonary vascular remodeling. We identified perivascular infiltration of CD3⁺ T cells and proinflammatory F4/80⁺ and CD68⁺ macrophages and proliferating cell nuclear antigen–positive alveolar epithelial cells all suppressed by TPHi treatment. Whole-lung mRNA sequencing in SuHx rats showed distinct gene expression patterns related to pulmonary arterial smooth muscle cell proliferation (Rpph1, Lgals3, Gata4), reactive oxygen species, inflammation (Tnfsrf17, iNOS), and vasodilation (Pde1b, Kng1), which reversed expression with TPHi treatment. Inhibition of TPH1 with a new class of drugs (here, TPT-001) has the potential to attenuate or even reverse severe PAH and associated RV dysfunction in vivo by blocking the serotonin pathway.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 890-902"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X2400175X/pdfft?md5=4e4774270d3ec22c79fc073ffef59952&pid=1-s2.0-S2452302X2400175X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141389680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Uses and Misuses of Mendelian Randomization in Clinical and Translational Science","authors":"Paul C. Lee MS, MSTP ,&nbsp;Douglas L. Mann MD ,&nbsp;Nathan O. Stitziel MD, PhD","doi":"10.1016/j.jacbts.2024.06.005","DOIUrl":"10.1016/j.jacbts.2024.06.005","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 935-938"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24002481/pdfft?md5=c6fff1f0bc7d843b09e2dcce5ff202b3&pid=1-s2.0-S2452302X24002481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141840079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetics and Pharmacogenetics of Atrial Fibrillation","authors":"","doi":"10.1016/j.jacbts.2023.12.006","DOIUrl":"10.1016/j.jacbts.2023.12.006","url":null,"abstract":"<div><p>The heritability of atrial fibrillation (AF) is well established. Over the last decade genetic architecture of AF has been unraveled by genome-wide association studies and family-based studies. However, the translation of these genetic discoveries has lagged owing to an incomplete understanding of the pathogenic mechanisms underlying the genetic variants, challenges in classifying variants of uncertain significance (VUS), and limitations of existing disease models. We review the mechanistic insight provided by basic science studies regarding AF mechanisms, recent developments in high-throughput classification of VUS, and advances in bioengineered cardiac models for developing personalized therapy for AF.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 918-934"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000032/pdfft?md5=8e8cd374accbaa0bed42435343824903&pid=1-s2.0-S2452302X24000032-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140466369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clopidogrel-Mediated P2Y12 Inhibition According to Renal Function in Patients With Diabetes Mellitus and CAD","authors":"","doi":"10.1016/j.jacbts.2024.03.003","DOIUrl":"10.1016/j.jacbts.2024.03.003","url":null,"abstract":"<div><p>This prospective ex vivo and in vitro pharmacodynamic (PD)/pharmacokinetic investigation was conducted in patients with diabetes mellitus with (n = 31) and without chronic kidney disease (n = 30). PD assessments included platelet reactivity index, maximum platelet aggregation, and P2Y₁₂ reaction units. Ex vivo pharmacokinetic assessments included plasma levels of clopidogrel and its active metabolite. In vitro PD assessments were conducted on baseline samples incubated with escalating concentrations of clopidogrel and its active metabolite. Among patients with diabetes mellitus treated with clopidogrel, impaired renal function was associated with increased maximum platelet aggregation. This finding could be attributed partially to upregulation of the P2Y₁₂ activity without differences in drug absorption or metabolism. (Impact of Chronic Kidney Disease on Clopidogrel Effects in Diabetes Mellitus; <span><span>NCT03774394</span><svg><path></path></svg></span>)</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 865-876"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000998/pdfft?md5=49959eebd33f5b556c9900664d0e659c&pid=1-s2.0-S2452302X24000998-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower Extremity Lymphatic Flow/Drainage Assessment by Indocyanine Green Fluorescent Lymphography in Heart Failure Patients","authors":"","doi":"10.1016/j.jacbts.2024.02.016","DOIUrl":"10.1016/j.jacbts.2024.02.016","url":null,"abstract":"<div><p>The purpose of this study was to present a protocol for visualizing lymphatic flow in patients with heart failure (HF) by using indocyanine green fluorescence lymphography. We studied 37 subjects: 20 patients with acute heart failure (AHF) and lower limb edema, 7 patients with chronic heart failure (CHF) without lower limb edema, and 10 control subjects (no HF, no limb edema). All subjects were assessed at rest, and 11 subjects (6 control and 5 with CHF) were assessed again after a 10-minute walk. The lymph flow was visualized in all selected patients without complications. At rest, there was either no lymph flow or minimal lymph flow in all control subjects and patients with CHF, whereas the majority of patients with AHF demonstrated significant lymph flow. This study describes a new method to visualize/assess lymphatic flow in patients with HF, allowing for continuous, real-time tracking of lymphatic flow in the lower extremity.</p></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 906-917"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X24000950/pdfft?md5=cf5f3bffacb0536cdc473b5471bce1ce&pid=1-s2.0-S2452302X24000950-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141132648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Inhibition of Peripheral Serotonin Synthesis in Pulmonary Hypertension","authors":"Olympia Bikou MD ,&nbsp;Katrin Schäfer MD","doi":"10.1016/j.jacbts.2024.05.009","DOIUrl":"10.1016/j.jacbts.2024.05.009","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"9 7","pages":"Pages 903-905"},"PeriodicalIF":8.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2452302X2400216X/pdfft?md5=8f19f50f39efa1e15662f6b3d4ffb2f9&pid=1-s2.0-S2452302X2400216X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141841612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}