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Mendelian Randomization Reveals Interleukin-6 Receptor-Lipoprotein(a) Interplay With Independent Cardiovascular Risk Reductions. 孟德尔随机化揭示白细胞介素-6受体-脂蛋白(a)相互作用与心血管风险降低。
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-05-08 DOI: 10.1016/j.jacbts.2026.101564
Azin Kheirkhah, Silvia Di Maio, Stefan Coassin, Sebastian Schönherr, Claudia Lamina, Lukas Forer, Florian Kronenberg, Johanna F Schachtl-Riess
{"title":"Mendelian Randomization Reveals Interleukin-6 Receptor-Lipoprotein(a) Interplay With Independent Cardiovascular Risk Reductions.","authors":"Azin Kheirkhah, Silvia Di Maio, Stefan Coassin, Sebastian Schönherr, Claudia Lamina, Lukas Forer, Florian Kronenberg, Johanna F Schachtl-Riess","doi":"10.1016/j.jacbts.2026.101564","DOIUrl":"https://doi.org/10.1016/j.jacbts.2026.101564","url":null,"abstract":"<p><p>In the study at hand, 2-sample Mendelian randomization supported a causal effect of interleukin-6 receptor (IL-6R) signaling on Lp(a) concentrations, revealing a direct interplay between 2 causal risk factors for cardiovascular disease (CVD). Importantly, epidemiological analyses in UK Biobank showed that neglecting the IL-6R functional state can confound the association between IL-6 levels and Lp(a). However, the effect of circulating IL-6 on Lp(a) concentrations was modest even when the functional state of the receptor was considered. In line, factorial Mendelian randomization indicated that down-regulation of IL-6R signaling and Lp(a) independently reduce CVD risk, highlighting complementary opportunities for CVD risk mitigation.</p>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":" ","pages":"101564"},"PeriodicalIF":8.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147838145","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}
引用次数: 0
Systems Biology Identifies TARS2 as a Cardiomyocyte Regulator of Mitochondrial Oxidative Stress in Dilated Cardiomyopathy 系统生物学鉴定TARS2是扩张型心肌病线粒体氧化应激的心肌细胞调节剂。
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-05-01 Epub Date: 2026-04-27 DOI: 10.1016/j.jacbts.2026.101535
Liming Chen PhD , Xuan Li PhD , Xiaolei Sun PhD , Xiaolin Wang PhD , Jian Wu PhD , Enyong Su PhD , Shijun Wang PhD , Huan Sun MD, PhD , Leilei Ma PhD , Yunzeng Zou MD, PhD
{"title":"Systems Biology Identifies TARS2 as a Cardiomyocyte Regulator of Mitochondrial Oxidative Stress in Dilated Cardiomyopathy","authors":"Liming Chen PhD ,&nbsp;Xuan Li PhD ,&nbsp;Xiaolei Sun PhD ,&nbsp;Xiaolin Wang PhD ,&nbsp;Jian Wu PhD ,&nbsp;Enyong Su PhD ,&nbsp;Shijun Wang PhD ,&nbsp;Huan Sun MD, PhD ,&nbsp;Leilei Ma PhD ,&nbsp;Yunzeng Zou MD, PhD","doi":"10.1016/j.jacbts.2026.101535","DOIUrl":"10.1016/j.jacbts.2026.101535","url":null,"abstract":"<div><div>Dilated cardiomyopathy (DCM), a leading cause of heart failure, is characterized by progressive cardiomyocyte (CM) loss and mitochondrial dysfunction; yet, the molecular drivers of mitochondrial oxidative stress (MitOS) remain unclear. By integrating bulk, single-cell, and spatial transcriptomics with machine learning, we identified threonyl-tRNA synthetase 2 (TARS2) as a CM-enriched regulator of MitOS. TARS2 was consistently up-regulated in human DCM hearts and associated with apoptotic signaling and enhanced macrophage crosstalk. Functional studies demonstrated that TARS2 overexpression disrupted mitochondrial homeostasis, triggered excessive mitochondrial reactive oxygen species, and induced CM apoptosis, whereas genetic inhibition restored mitochondrial function, reduced apoptosis, and improved cardiac performance. These findings uncover TARS2 as a novel regulator of mitochondrial dysfunction and pathological remodeling in DCM, providing both mechanistic insights and therapeutic implications, and establish a systems biology framework for translational discovery of disease targets in cardiovascular medicine.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 5","pages":"Article 101535"},"PeriodicalIF":8.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772026","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}
引用次数: 0
Cardiomyocyte-Derived Apelin Rescues Viral Myocarditis-Induced Cardiac Lymphatic Dysfunction and Remodeling 心肌细胞来源的Apelin拯救病毒性心肌炎诱导的心脏淋巴功能障碍和重塑。
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-05-01 Epub Date: 2026-04-27 DOI: 10.1016/j.jacbts.2026.101537
Yuan-Nan Lin MD , Jing Xu MD , Yi-Hao Wu MD , Mao-Xiang Jin MD , Yu-Tian Wang MD , Yu-Qing Wu MD , Hao-Hua Zhan MD , Xin-Ge Qian MD , Zhe-Ning Wang MD , Lei-Wang MD , Yue-Chun Li MD
{"title":"Cardiomyocyte-Derived Apelin Rescues Viral Myocarditis-Induced Cardiac Lymphatic Dysfunction and Remodeling","authors":"Yuan-Nan Lin MD ,&nbsp;Jing Xu MD ,&nbsp;Yi-Hao Wu MD ,&nbsp;Mao-Xiang Jin MD ,&nbsp;Yu-Tian Wang MD ,&nbsp;Yu-Qing Wu MD ,&nbsp;Hao-Hua Zhan MD ,&nbsp;Xin-Ge Qian MD ,&nbsp;Zhe-Ning Wang MD ,&nbsp;Lei-Wang MD ,&nbsp;Yue-Chun Li MD","doi":"10.1016/j.jacbts.2026.101537","DOIUrl":"10.1016/j.jacbts.2026.101537","url":null,"abstract":"<div><div>Recent research has indicated that cardiac lymphatic vessels (CLVs) serve as a direct drainage route into the mediastinal lymph nodes for inflammation resolution. However, the role of CLVs in coxsackievirus B3–induced acute viral myocarditis (AVMC) remains unknown. In this study, we found that AVMC in mice promoted pathological cardiac lymphangiogenesis while impairing CLV-mediated drainage, leading to heart inflammation and dysfunction. Overexpression of apelin in cardiomyocytes improved CLV integrity and promoted effective lymph drainage to decrease inflammatory responses and enhance cardiac function. In vitro studies revealed that apelin stabilizes lymphatic endothelial cadherin and zonula occludens 1 to enhance lymphatic function via the AKT signaling pathway. Moreover, pre-existing lymphatic defects induced by blocking vascular endothelial growth factor receptor 3 partially diminished the benefits of cardiomyocyte-derived apelin overexpression in AVMC. Taken together, these data indicate that functional CLVs restored by cardiomyocyte-derived apelin facilitate inflammation resolution and improve heart dysfunction in AVMC. Thus, CLV-based therapeutic strategies may serve as a novel approach for alleviating AVMC heart damage.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 5","pages":"Article 101537"},"PeriodicalIF":8.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771871","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}
引用次数: 0
PD-1/PD-L1 Signaling in Non-ICI Myocarditis. PD-1/PD-L1信号在非ici心肌炎中的作用。
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-19 DOI: 10.1016/j.jacbts.2026.101539
Laura I Yousif, Aukje G Sijtema, Ymke Appels, Pieter F van den Berg, Joseph Pierre Aboumsallem, Olivier C Manintveld, Dirk J Duncker, Rudolf A de Boer, Wouter C Meijers
{"title":"PD-1/PD-L1 Signaling in Non-ICI Myocarditis.","authors":"Laura I Yousif, Aukje G Sijtema, Ymke Appels, Pieter F van den Berg, Joseph Pierre Aboumsallem, Olivier C Manintveld, Dirk J Duncker, Rudolf A de Boer, Wouter C Meijers","doi":"10.1016/j.jacbts.2026.101539","DOIUrl":"https://doi.org/10.1016/j.jacbts.2026.101539","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI)-mediated myocarditis is a notorious complication of cancer treatment; however, the role of immune checkpoints in the heart during inflammation remains unknown. We investigated myocardial expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in non-ICI myocarditis. We performed a cross-species single-cell/-nucleus RNA sequencing comparative analysis, including 3 different models of myocarditis in mice and human hearts, with in vitro validation in human cells. This provided compelling evidence that PD-1/PD-L1 signaling in both murine and human non-ICI myocarditis is inherent to the myocardial inflammatory response. Specifically, cardiac endothelial cells and fibroblasts exhibited robust and sustained PD-L1 up-regulation in myocarditis, while also coinciding temporally with peak PD-1 expression on T cells, which presents an important defense mechanism. Therefore, immune checkpoints have global importance in myocarditis and may serve as a therapeutic target.</p>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":" ","pages":"101539"},"PeriodicalIF":8.4,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723050","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}
引用次数: 0
Metabolic Reprogramming of Fibroblasts by Extracellular Vesicles 细胞外囊泡对成纤维细胞的代谢重编程：纤维化的治疗轴。
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-01 Epub Date: 2026-04-27 DOI: 10.1016/j.jacbts.2026.101538
Yu Tian MS , Andrew A. Gibb PhD
{"title":"Metabolic Reprogramming of Fibroblasts by Extracellular Vesicles","authors":"Yu Tian MS ,&nbsp;Andrew A. Gibb PhD","doi":"10.1016/j.jacbts.2026.101538","DOIUrl":"10.1016/j.jacbts.2026.101538","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 4","pages":"Article 101538"},"PeriodicalIF":8.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771848","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}
引用次数: 0
Full Issue PDF 完整版PDF
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-01 Epub Date: 2026-04-27 DOI: 10.1016/S2452-302X(26)00069-0
{"title":"Full Issue PDF","authors":"","doi":"10.1016/S2452-302X(26)00069-0","DOIUrl":"10.1016/S2452-302X(26)00069-0","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 4","pages":"Article 101551"},"PeriodicalIF":8.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797883","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}
引用次数: 0
Pillars of Peer Review 同行评议的支柱。
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-01 Epub Date: 2026-04-27 DOI: 10.1016/j.jacbts.2026.101531
Matthias Nahrendorf MD, PhD (Editor-in-Chief, JACC: Basic to Translational Science)
{"title":"Pillars of Peer Review","authors":"Matthias Nahrendorf MD, PhD (Editor-in-Chief, JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2026.101531","DOIUrl":"10.1016/j.jacbts.2026.101531","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 4","pages":"Article 101531"},"PeriodicalIF":8.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771776","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}
引用次数: 0
Is Obesity a Major Driver of Primary Aldosteronism? 肥胖是原发性醛固酮增多症的主要驱动因素吗？
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-01 Epub Date: 2026-04-27 DOI: 10.1016/j.jacbts.2026.101541
John E. Hall PhD , Ana C.M. Omoto PhD , Michael E. Hall MD, MS
{"title":"Is Obesity a Major Driver of Primary Aldosteronism?","authors":"John E. Hall PhD ,&nbsp;Ana C.M. Omoto PhD ,&nbsp;Michael E. Hall MD, MS","doi":"10.1016/j.jacbts.2026.101541","DOIUrl":"10.1016/j.jacbts.2026.101541","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 4","pages":"Article 101541"},"PeriodicalIF":8.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147771845","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}
引用次数: 0
Methylated PIH1D1 as a Heart-Specific Biomarker for Anthracycline-Induced Cardiac Remodeling in Breast Cancer Patients 甲基化pihd1作为蒽环类药物诱导乳腺癌患者心脏重构的心脏特异性生物标志物
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-01 Epub Date: 2026-03-11 DOI: 10.1016/j.jacbts.2026.101510
Po-Yen Hsu MS , Wan-Hong Huang MS , Yi-Yun Lee BS , Robert Passier PhD , Szu-Chin Li MD, PhD , Chong-Lin Hong MD, PhD , Shih-Kai Hung MD, PhD , Hong-Yi Lin MD, PhD , Chun-Hung Lin MD , Chen-Yu Chien MD , Yi-Da Li MD, MS , Hsiang-Chun Lee MD, PhD , Laurent Désaubry PhD , Canan G. Nebigil PhD , Michael W.Y. Chan PhD
{"title":"Methylated PIH1D1 as a Heart-Specific Biomarker for Anthracycline-Induced Cardiac Remodeling in Breast Cancer Patients","authors":"Po-Yen Hsu MS ,&nbsp;Wan-Hong Huang MS ,&nbsp;Yi-Yun Lee BS ,&nbsp;Robert Passier PhD ,&nbsp;Szu-Chin Li MD, PhD ,&nbsp;Chong-Lin Hong MD, PhD ,&nbsp;Shih-Kai Hung MD, PhD ,&nbsp;Hong-Yi Lin MD, PhD ,&nbsp;Chun-Hung Lin MD ,&nbsp;Chen-Yu Chien MD ,&nbsp;Yi-Da Li MD, MS ,&nbsp;Hsiang-Chun Lee MD, PhD ,&nbsp;Laurent Désaubry PhD ,&nbsp;Canan G. Nebigil PhD ,&nbsp;Michael W.Y. Chan PhD","doi":"10.1016/j.jacbts.2026.101510","DOIUrl":"10.1016/j.jacbts.2026.101510","url":null,"abstract":"<div><div>Anthracyclines, key chemotherapy agents, pose cardiotoxicity risks. In a 3-year study of 89 breast cancer patients treated with doxorubicin or epirubicin, more than 50% showed reduced left ventricular ejection fraction and progressive ventricular dilation. Although troponin-I flagged acute damage, it failed to predict long-term remodeling. Using a human methylome atlas, researchers identified 33 heart-specific methylated CpG sites and validated methylated <em>PIH1D1</em> (m<em>PIH1D1</em>) as a novel biomarker. Elevated m<em>PIH1D1</em> levels strongly correlated with ventricular dilation but not left ventricular ejection fraction decline, indicating its sensitivity to early cardiac remodeling. m<em>PIH1D1</em> may complement troponin-I in risk assessment and cardiotoxicity management for patients undergoing anthracycline-based chemotherapy.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 4","pages":"Article 101510"},"PeriodicalIF":8.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147387943","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}
引用次数: 0
JACC: Basic to Translational Science 2025 Thomas Force Young Investigator Award Winner JACC：基础到转化科学2025年Thomas Force青年研究者奖得主
IF 8.4 1区 医学
JACC: Basic to Translational Science Pub Date : 2026-04-01 Epub Date: 2026-04-27 DOI: 10.1016/j.jacbts.2026.101529
Matthias Nahrendorf MD, PhD (Editor-in-Chief: JACC: Basic to Translational Science)
{"title":"JACC: Basic to Translational Science 2025 Thomas Force Young Investigator Award Winner","authors":"Matthias Nahrendorf MD, PhD (Editor-in-Chief: JACC: Basic to Translational Science)","doi":"10.1016/j.jacbts.2026.101529","DOIUrl":"10.1016/j.jacbts.2026.101529","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"11 4","pages":"Article 101529"},"PeriodicalIF":8.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147797881","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}
引用次数: 0
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