Lan Gao PhD , Qindong Shi PhD , Bin Sun MD , Xiaoyu Zhang MD , Peiying Zheng MD , Linjing Zhou MD , Gang Tian PhD , Hao Li PhD
{"title":"c-FLIP Protects Cardiac Microcirculation in Sepsis-Induced Myocardial Dysfunction Via FUNDC1-Mediated Regulation of Mitochondrial Autophagy","authors":"Lan Gao PhD , Qindong Shi PhD , Bin Sun MD , Xiaoyu Zhang MD , Peiying Zheng MD , Linjing Zhou MD , Gang Tian PhD , Hao Li PhD","doi":"10.1016/j.jacbts.2025.02.016","DOIUrl":"10.1016/j.jacbts.2025.02.016","url":null,"abstract":"<div><div>This study investigates the role of c-FLIP in sepsis-induced myocardial dysfunction (SIMD), focusing on cardiac microcirculation and mitochondrial autophagy. Using SIMD rat and LPS-induced cardiac microvascular endothelial cell injury models, we found that c-FLIP deficiency disrupts mitochondrial homeostasis, exacerbating microcirculatory damage. c-FLIP differentially regulates mitochondrial autophagy via FUNDC1. Overexpression of c-FLIP balances autophagy, protects mitochondria, reduces inflammation, and ameliorates SIMD, highlighting its potential as a therapeutic target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101257"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078023","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}
Jun-Zhuo Shi MS , Yong-Jian Zhu MD , Meng-Jie Zhang BS , Yi Yan PhD , Lu-Ling Zhao MS , Hong-Da Zhang MD , Yan Liu MD , Wen-Hui Wu PhD , Zhe Cheng MD , Chun-Guang Qiu MD , Jie-Jian Kou MS , Yun-Feng Zhou PhD , Xiao-Bin Pang PhD , Ji-Wang Chen MD , Xin-Mei Xie MS , Yang-Yang He PhD , Zhi-Cheng Jing MD
{"title":"Hypoxanthine Promotes Pulmonary Vascular Remodeling and Adenosine Deaminase Is a Therapeutic Target for Pulmonary Hypertension","authors":"Jun-Zhuo Shi MS , Yong-Jian Zhu MD , Meng-Jie Zhang BS , Yi Yan PhD , Lu-Ling Zhao MS , Hong-Da Zhang MD , Yan Liu MD , Wen-Hui Wu PhD , Zhe Cheng MD , Chun-Guang Qiu MD , Jie-Jian Kou MS , Yun-Feng Zhou PhD , Xiao-Bin Pang PhD , Ji-Wang Chen MD , Xin-Mei Xie MS , Yang-Yang He PhD , Zhi-Cheng Jing MD","doi":"10.1016/j.jacbts.2025.03.005","DOIUrl":"10.1016/j.jacbts.2025.03.005","url":null,"abstract":"<div><div>Uric acid metabolism is implicated in the pathogenesis of pulmonary arterial hypertension, wherein the key metabolite hypoxanthine exhibits elevated levels, thereby promoting pulmonary vascular remodeling through facilitation of cell proliferation and migration as well as regulation of adenosine triphosphate binding cassette transport signaling pathway. Consequently, therapeutic interventions targeting hypoxanthine synthesis may hold promise for the management of pulmonary arterial hypertension.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101273"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896126","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}
María Valero-Muñoz PhD, Eng Leng Saw PhD, Hannah Cooper BA, David R. Pimentel MD, Flora Sam MD
{"title":"White Adipose Tissue in Obesity-Associated HFpEF","authors":"María Valero-Muñoz PhD, Eng Leng Saw PhD, Hannah Cooper BA, David R. Pimentel MD, Flora Sam MD","doi":"10.1016/j.jacbts.2025.02.021","DOIUrl":"10.1016/j.jacbts.2025.02.021","url":null,"abstract":"<div><div>Obesity and hypertension are prevalent comorbidities in heart failure with preserved ejection fraction (HFpEF). Increased adiposity is implicated in its pathophysiology. We investigated changes in white adipose tissue (WAT) in obesity-associated HFpEF utilizing patient samples and a murine model of obesity-associated HFpEF. WAT analysis revealed \"browning\", characterized by smaller adipocytes and increased UCP1 expression, alongside fibrosis and reduced vascular markers during acute HF decompensation. During chronic, stable HFpEF, “browning” markers declined. There is a dynamic process in WAT, where acute HF exacerbations trigger transient “browning”, fibrosis, and vascular deterioration, which partially reverse but fibrosis persists. WAT dysfunction worsens during acute HF, highlighting a potential therapeutic target for obesity-related HFpEF.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101262"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019452","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":"Periodontitis Accelerates Progression of Heart Failure With Preserved Ejection Fraction in Mice","authors":"Samar Daana MSc , Yair Rokach PhD , Suzan Abedat PhD , Dean Nachman MD , Hadeya Mohsen BSc , Sama Karram DMD, MSc , Yael Zandberg DMD , Rinat Tzach-Nachman DMD, PhD , Jonathan Cohen MD, PhD , Offer Amir MD , Yael Houri-Haddad DMD, PhD , Rabea Asleh MD, PhD, MHA","doi":"10.1016/j.jacbts.2025.03.002","DOIUrl":"10.1016/j.jacbts.2025.03.002","url":null,"abstract":"<div><div>Chronic low-grade inflammation and nitric oxide (NO) depletion are important contributors to heart failure with preserved ejection fraction (HFpEF) pathophysiology. Periodontitis (PD) is a common inflammatory disease implicated in dysregulation of NO hemostasis. Epidemiological studies have shown an association between PD and increased risk of cardiovascular disease, including heart failure. However, a causative relationship between the 2 diseases has not yet been proven. In this study, we sought to investigate the direct effect of PD induction on HFpEF progression in a mouse model. Induction of PD in HFpEF mice resulted in significant oral microbial dysbiosis, accelerated progression of diastolic dysfunction by echocardiography, and increased myocardial inflammation and fibrosis. These deleterious effects seen with PD were shown to be mediated by increased systemic blood pressure, increased systemic inflammation, and NO depletion. Our study provides evidence of potential mechanistic links between PD and HFpEF progression and suggests PD as a new therapeutic target for HFpEF.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101270"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274902","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}
Ao Liu MD, PhD , Peiyuan Bai MD, PhD , Hongmin You MD , Zehao Zhuang MD , Fangyan Tian MD, PhD , Haobo Weng MD, PhD , Xuemei Wei MD , Lu Tang MD , Litao Wang MD, PhD , Chaobao Liu MD , Jinghong Zhang MD , Minmin Sun MD, PhD , Shuning Zhang MD, PhD , Xianhong Shu MD, PhD , Junbo Ge MD, PhD
{"title":"SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity","authors":"Ao Liu MD, PhD , Peiyuan Bai MD, PhD , Hongmin You MD , Zehao Zhuang MD , Fangyan Tian MD, PhD , Haobo Weng MD, PhD , Xuemei Wei MD , Lu Tang MD , Litao Wang MD, PhD , Chaobao Liu MD , Jinghong Zhang MD , Minmin Sun MD, PhD , Shuning Zhang MD, PhD , Xianhong Shu MD, PhD , Junbo Ge MD, PhD","doi":"10.1016/j.jacbts.2025.02.015","DOIUrl":"10.1016/j.jacbts.2025.02.015","url":null,"abstract":"<div><div>Doxorubicin-induced cardiotoxicity (DIC) poses a significant challenge in cancer treatment. This study investigated the role of SLAMF7 in DIC, particularly in macrophage-mediated inflammation. Using SLAMF7 knockout mice, we found that SLAMF7 deficiency exacerbates DIC and amplifies inflammatory responses. Mechanistically, SLAMF7 interacts with TNF receptor-associated factor 6 to attenuate nuclear factor κB signaling, reducing oxidative stress and proinflammatory cytokines. Notably, administering recombinant SLAMF7 protein effectively mitigated DIC. These findings underscore the critical role of SLAMF7 in protecting against DIC, positioning it as a promising therapeutic target.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101256"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078027","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}
Xing Luo PhD , Ji Li PhD , Yuwu Chen MD , Xiuzhu Weng MD , Xiaoyi Bao PhD , Xiaoxuan Bai MD , Ying Lv PhD , Shan Zhang PhD , Xinxin Zhu MD , Biyi Xu MD , Chen Zhao MD , Ming Zeng MD , Tianyu Wu MD , Qianhui Sun MD , Shengfang Wang PhD , Minghao Liu MD , Thomas Johnson PhD , Stephen J. White PhD , Peter Libby MD , Sining Hu PhD , Haibo Jia PhD
{"title":"Cigarette Tar Enhanced ECs Pyroptosis via CAMKII/Drp1/mtDNA","authors":"Xing Luo PhD , Ji Li PhD , Yuwu Chen MD , Xiuzhu Weng MD , Xiaoyi Bao PhD , Xiaoxuan Bai MD , Ying Lv PhD , Shan Zhang PhD , Xinxin Zhu MD , Biyi Xu MD , Chen Zhao MD , Ming Zeng MD , Tianyu Wu MD , Qianhui Sun MD , Shengfang Wang PhD , Minghao Liu MD , Thomas Johnson PhD , Stephen J. White PhD , Peter Libby MD , Sining Hu PhD , Haibo Jia PhD","doi":"10.1016/j.jacbts.2025.03.015","DOIUrl":"10.1016/j.jacbts.2025.03.015","url":null,"abstract":"<div><div>Smoking is the only cardiovascular risk factor for plaque erosion. We found cigarette tar resulted in erosion-like lesion development in apolipoprotein E<sup>−/−</sup> mice, with mural thrombosis, discontinuous endothelium, platelet activation, smooth muscle cell proliferation, and hyaluronic acid accumulation in the aorta. Single-cell transcriptomics revealed that genes relating to pyroptosis, platelet activation, and leukocytes adhesion were significantly increased in an endothelial cell subset. Rescue assays indicated cigarette tar caused human coronary artery endothelial cell pyroptosis by enhanced calcium–calmodulin-dependent protein kinase II / dynamin-related protein 1–mediated mitochondrial fission and mitochondrial DNA release via activating Ca<sup>2+</sup> signaling. Inhibition of endothelial cell pyroptosis may be a novel therapeutic strategy to reduce plaque erosion.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101283"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896128","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}
Nipun Malhotra MSc , Omer Cavus MD , Michael J. Wallace BS , John T. Bobik BS , Kevin You , Sarah S. Takenaka BS , Danielle Abdallah BS , Eleanor J. Mohler , Steve Antwi-Boasiako BS , Nathaniel P. Murphy MD, PhD , Holly Sucharski-Argall PhD , Xianyao Xu MSc , Stephen P. Chelko PhD , Thomas J. Hund PhD , Jason D. Roberts MD, MAS , Peter J. Mohler PhD , Mona El Refaey PhD
{"title":"Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy","authors":"Nipun Malhotra MSc , Omer Cavus MD , Michael J. Wallace BS , John T. Bobik BS , Kevin You , Sarah S. Takenaka BS , Danielle Abdallah BS , Eleanor J. Mohler , Steve Antwi-Boasiako BS , Nathaniel P. Murphy MD, PhD , Holly Sucharski-Argall PhD , Xianyao Xu MSc , Stephen P. Chelko PhD , Thomas J. Hund PhD , Jason D. Roberts MD, MAS , Peter J. Mohler PhD , Mona El Refaey PhD","doi":"10.1016/j.jacbts.2025.03.013","DOIUrl":"10.1016/j.jacbts.2025.03.013","url":null,"abstract":"<div><div>Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease, and current pharmacological therapies are directed toward the management of electrical manifestations. To date, none address the underlying pathophysiology of this progressive condition. We evaluated the therapeutic efficacy of Tideglusib (TD) in Ank2 cardio-selective-knockout and homozygous desmoglein-2 mutant ACM mouse models. TD was able to prevent and reverse the reduced cardiac function in treated mice. Moreover, TD-treated adult mice displayed a reduction in ventricular arrhythmia following adrenergic stimulation. We provide compelling preclinical data for TD as a potential therapy for patients with ACM.</div></div>","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101281"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896068","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":"Exploring Mechanisms of Pulmonary Artery Banding in a Rat Model of Dilated Cardiomyopathy","authors":"Yi Ye PhD, Veli K. Topkara MD, MSc","doi":"10.1016/j.jacbts.2025.04.017","DOIUrl":"10.1016/j.jacbts.2025.04.017","url":null,"abstract":"","PeriodicalId":14831,"journal":{"name":"JACC: Basic to Translational Science","volume":"10 8","pages":"Article 101303"},"PeriodicalIF":8.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896123","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}
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