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Loss of the Atrial Fibrillation-Related Gene, Zfhx3, Results in Atrial Dilation and Arrhythmias. Circ. Res. (IF 20.1) Pub Date : 2023-07-14 Heather S Jameson,Alan Hanley,Matthew C Hill,Ling Xiao,Jiangchuan Ye,Aneesh Bapat,Elsa Ronzier,Amelia Weber Hall,William J Hucker,Sebastian Clauss,Miranda Barazza,Elizabeth Silber,Julie Mina,Nathan R Tucker,Robert W Mills,Jin-Tang Dong,David J Milan,Patrick T Ellinor
BACKGROUND ZFHX3, a gene that encodes a large transcription factor, is at the second-most significantly associated locus with atrial fibrillation (AF), but its function in the heart is unknown. This study aims to identify causative genetic variation related to AF at the ZFHX3 locus and examine the impact of Zfhx3 loss on cardiac function in mice. METHODS CRISPR-Cas9 genome editing, chromatin immunoprecipitation
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Impact of BNT162b2 and mRNA-1273 Vaccination on Vascular Function in Healthy Adults: A Pilot Study. Circ. Res. (IF 20.1) Pub Date : 2023-07-13 Corinna Serviente,Alexs Matias,Mia Calderone,Muhammet Enes Erol,Stuart Chipkin,Gwenael Layec
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CTLA-4 Pathway Is Instrumental in Giant Cell Arteritis. Circ. Res. (IF 20.1) Pub Date : 2023-07-12 Paul Régnier,Alexandre Le Joncour,Anna Maciejewski-Duval,Guillaume Darrasse-Jèze,Charles Dolladille,Wouter C Meijers,Lisa Bastarache,Pierre Fouret,Patrick Bruneval,Floriane Arbaretaz,Célia Sayetta,Ana Márquez,Michelle Rosenzwajg,David Klatzmann,Patrice Cacoub,Javid J Moslehi,Joe-Elie Salem,David Saadoun
BACKGROUND Giant cell arteritis (GCA) causes severe inflammation of the aorta and its branches and is characterized by intense effector T-cell infiltration. The roles that immune checkpoints play in the pathogenesis of GCA are still unclear. Our aim was to study the immune checkpoint interplay in GCA. METHODS First, we used VigiBase, the World Health Organization international pharmacovigilance database
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Correction to: Use of Computation Ecosystems to Analyze the Kidney-Heart Crosstalk. Circ. Res. (IF 20.1) Pub Date : 2023-07-06
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Vicious Twins: RyR2 Dysfunction and Structural Remodeling. Circ. Res. (IF 20.1) Pub Date : 2023-07-06 Niels Voigt,Fitzwilliam Seibertz,Funsho E Fakuade
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P53 Regulates the Extent of Fibroblast Proliferation and Fibrosis in Left Ventricle Pressure Overload. Circ. Res. (IF 20.1) Pub Date : 2023-07-06 Xiaoyi Liu,Ryan M Burke,Janet K Lighthouse,Cameron D Baker,Ronald A Dirkx,Brian Kang,Yashoswini Chakraborty,Deanne M Mickelsen,Jennifer Twardowski,Stephano S Mello,John M Ashton,Eric M Small
BACKGROUND Cardiomyopathy is characterized by the pathological accumulation of resident cardiac fibroblasts that deposit ECM (extracellular matrix) and generate a fibrotic scar. However, the mechanisms that control the timing and extent of cardiac fibroblast proliferation and ECM production are not known, hampering the development of antifibrotic strategies to prevent heart failure. METHODS We used
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Stretch Harmonizes Sarcomere Strain Across the Cardiomyocyte. Circ. Res. (IF 20.1) Pub Date : 2023-07-04 Jia Li,Joakim Sundnes,Yufeng Hou,Martin Laasmaa,Marianne Ruud,Andreas Unger,Terje R Kolstad,Michael Frisk,Per A Norseng,Limin Yang,Ingunn E Setterberg,Estela S Alves,Michaeljohn Kalakoutis,Ole M Sejersted,Johanna T Lanner,Wolfgang A Linke,Ida G Lunde,Pieter P de Tombe,William E Louch
BACKGROUND Increasing cardiomyocyte contraction during myocardial stretch serves as the basis for the Frank-Starling mechanism in the heart. However, it remains unclear how this phenomenon occurs regionally within cardiomyocytes, at the level of individual sarcomeres. We investigated sarcomere contractile synchrony and how intersarcomere dynamics contribute to increasing contractility during cell lengthening
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Development of a Translational Autologous Microthrombi-Induced MINOCA Pig Model. Circ. Res. (IF 20.1) Pub Date : 2023-07-03 Nikola Cesarovic,Miriam Weisskopf,Thorald Stolte,Nina Trimmel,Melanie M Hierweger,Tobias Hoh,Jasper Iske,Conny Waschkies,Jia Lu Chen,Eva van Gelder,Andrea Leuthardt,Lukas Glaus,Yannick Rösch,Christian T Stoeck,Petra Wolint,Dominik Obrist,Sebastian Kozerke,Volkmar Falk,Maximilian Y Emmert
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Renin Cell Development: Insights From Chromatin Accessibility and Single-Cell Transcriptomics. Circ. Res. (IF 20.1) Pub Date : 2023-07-03 Alexandre G Martini,Jason P Smith,Silvia Medrano,Gal Finer,Nathan C Sheffield,Maria Luisa S Sequeira-Lopez,R Ariel Gomez
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Mitochondrial GSNOR Alleviates Cardiac Dysfunction via ANT1 Denitrosylation. Circ. Res. (IF 20.1) Pub Date : 2023-06-28 Xin Tang,Shuang Zhao,Jieqiong Liu,Xiameng Liu,Xinqi Sha,Changgao Huang,Lulu Hu,Shixiu Sun,Yuanqing Gao,Hongshan Chen,Zhiren Zhang,Dongjin Wang,Yuexi Gu,Shaoliang Chen,Liansheng Wang,Aihua Gu,Feng Chen,Jun Pu,Xin Chen,Bo Yu,Liping Xie,Zhengrong Huang,Yi Han,Yong Ji
BACKGROUND The cardiac-protective role of GSNOR (S-nitrosoglutathione reductase) in the cytoplasm, as a denitrosylase enzyme of S-nitrosylation, has been reported in cardiac remodeling, but whether GSNOR is localized in other organelles and exerts novel effects remains unknown. We aimed to elucidate the effects of mitochondrial GSNOR, a novel subcellular localization of GSNOR, on cardiac remodeling
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Loss of Macrophage mTORC2 Drives Atherosclerosis via FoxO1 and IL-1β Signaling. Circ. Res. (IF 20.1) Pub Date : 2023-06-23 Xiangyu Zhang,Trent D Evans,Sunny Chen,Ismail Sergin,Jeremiah Stitham,Se-Jin Jeong,Astrid Rodriguez-Velez,Yu-Sheng Yeh,Arick Park,In-Hyuk Jung,Abhinav Diwan,Joel D Schilling,Oren Rom,Arif Yurdagul,Slava Epelman,Jaehyung Cho,Irfan J Lodhi,Bettina Mittendorfer,Babak Razani
BACKGROUND The mTOR (mechanistic target of rapamycin) pathway is a complex signaling cascade that regulates cellular growth, proliferation, metabolism, and survival. Although activation of mTOR signaling has been linked to atherosclerosis, its direct role in lesion progression and in plaque macrophages remains poorly understood. We previously demonstrated that mTORC1 (mTOR complex 1) activation promotes
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A Novel Role for FKBP5 in Atrial Cardiomyopathy. Circ. Res. (IF 20.1) Pub Date : 2023-06-22 Diane Fatkin,Monique Ohanian,Kemar J Brown
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Correction to: Cell-Specific Mechanisms in the Heart of COVID-19 Patients. Circ. Res. (IF 20.1) Pub Date : 2023-06-22
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DRP1-Mediated Mitophagy: Safeguarding Obese Hearts From Cardiomyopathy. Circ. Res. (IF 20.1) Pub Date : 2023-06-22 Xi Fang,Åsa B Gustafsson
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TGF-β1/SMAD3 Regulates Programmed Cell Death 5 That Suppresses Cardiac Fibrosis Post-Myocardial Infarction by Inhibiting HDAC3. Circ. Res. (IF 20.1) Pub Date : 2023-06-22 Lin Weng,Jingjing Ye,Fenghe Yang,Shi Jia,Minghong Leng,Bo Jia,Chunling Xu,Yang Zhao,Ruxia Liu,Yufei Xiong,Yiqing Zhou,Junhui Zhao,Ming Zheng
BACKGROUND Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying
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Increased Ca2+ Transient Underlies RyR2-Related Left Ventricular Noncompaction. Circ. Res. (IF 20.1) Pub Date : 2023-06-16 Mingke Ni,Yanhui Li,Jinhong Wei,Zhenpeng Song,Hui Wang,Jinjing Yao,Yong-Xiang Chen,Darrell Belke,John Paul Estillore,Ruiwu Wang,Alexander Vallmitjana,Raul Benitez,Leif Hove-Madsen,Wei Feng,Ju Chen,Thomas M Roston,Shubhayan Sanatani,Anna Lehman,S R Wayne Chen
BACKGROUND A loss-of-function cardiac ryanodine receptor (RyR2) mutation, I4855M+/-, has recently been linked to a new cardiac disorder termed RyR2 Ca2+ release deficiency syndrome (CRDS) as well as left ventricular noncompaction (LVNC). The mechanism by which RyR2 loss-of-function causes CRDS has been extensively studied, but the mechanism underlying RyR2 loss-of-function-associated LVNC is unknown
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iPSC-Based Modeling of Variable Clinical Presentation in Hypertrophic Cardiomyopathy. Circ. Res. (IF 20.1) Pub Date : 2023-06-15 Rubén Escribá,José M Larrañaga-Moreira,Yvonne Richaud-Patin,Léa Pourchet,Ioannis Lazis,Senda Jiménez-Delgado,Alba Morillas-García,Martín Ortiz-Genga,Juan Pablo Ochoa,David Carreras,Guillermo Javier Pérez,José Luis de la Pompa,Ramón Brugada,Lorenzo Monserrat,Roberto Barriales-Villa,Angel Raya
BACKGROUND Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation
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An Alternative Mechanism of Subcellular Iron Uptake Deficiency in Cardiomyocytes. Circ. Res. (IF 20.1) Pub Date : 2023-06-14 Yuanyuan Dai,Nadezda Ignatyeva,Hang Xu,Ruheen Wali,Karl Toischer,Sören Brandenburg,Christof Lenz,Julius Pronto,Funsho E Fakuade,Samuel Sossalla,Elisabeth M Zeisberg,Andreas Janshoff,Ingo Kutschka,Niels Voigt,Henning Urlaub,Torsten Bloch Rasmussen,Jens Mogensen,Stephan E Lehnart,Gerd Hasenfuss,Antje Ebert
BACKGROUND Systemic defects in intestinal iron absorption, circulation, and retention cause iron deficiency in 50% of patients with heart failure. Defective subcellular iron uptake mechanisms that are independent of systemic absorption are incompletely understood. The main intracellular route for iron uptake in cardiomyocytes is clathrin-mediated endocytosis. METHODS We investigated subcellular iron
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Functional LTCC-β2AR Complex Needs Caveolin-3 and Is Disrupted in Heart Failure. Circ. Res. (IF 20.1) Pub Date : 2023-06-14 Jose L Sanchez-Alonso,Laura Fedele,Jaël S Copier,Carla Lucarelli,Catherine Mansfield,Aleksandra Judina,Steven R Houser,Thomas Brand,Julia Gorelik
BACKGROUND Beta-2 adrenergic receptors (β2ARs) but not beta-2 adrenergic receptors (β1ARs) form a functional complex with L-type Ca2+ channels (LTCCs) on the cardiomyocyte membrane. However, how microdomain localization in the plasma membrane affects the function of these complexes is unknown. We aim to study the coupling between LTCC and β adrenergic receptors in different cardiomyocyte microdomains
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Genomic Innovation in Early Life Cardiovascular Disease Prevention and Treatment. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Changwei Li,Yang Pan,Ruiyuan Zhang,Zhijie Huang,Davey Li,Yunan Han,Claire Larkin,Varun Rao,Xiao Sun,Tanika N Kelly
Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Although CVD events do not typically manifest until older adulthood, CVD develops gradually across the life-course, beginning with the elevation of risk factors observed as early as childhood or adolescence and the emergence of subclinical disease that can occur in young adulthood or midlife. Genomic background, which
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Life Course Cardiovascular Health: Risk Factors, Outcomes, and Interventions. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Havisha Pedamallu,Rachel Zmora,Amanda M Perak,Norrina B Allen
Since it was first defined by the American Heart Association in 2010, cardiovascular health (CVH) has been extensively studied across the life course. In this review, we present the current literature examining early life predictors of CVH, the later life outcomes of child CVH, and the relatively few interventions which have specifically addressed how to preserve and promote CVH across populations
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Diet and Food and Nutrition Insecurity and Cardiometabolic Disease. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Eric J Brandt,Dariush Mozaffarian,Cindy W Leung,Seth A Berkowitz,Venkatesh L Murthy
Poor nutrition is the leading cause of poor health, health care spending, and lost productivity in the United States and globally, which acts through cardiometabolic diseases as precursors to cardiovascular disease, cancer, and other conditions. There is great interest in how the social determinants of health (the conditions in which people are born, live, work, develop, and age) impact cardiometabolic
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Physical Activity Over the Lifecourse and Cardiovascular Disease. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Andrew S Perry,Erin E Dooley,Hiral Master,Nicole L Spartano,Evan L Brittain,Kelley Pettee Gabriel
Despite improvements in cardiovascular care in recent decades, cardiovascular disease (CVD) remains a leading cause of death worldwide. At its core, CVD is a largely preventable disease with diligent risk factor management and early detection. As highlighted in the American Heart Association's Life's Essential 8, physical activity plays a central role in CVD prevention at an individual and population
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Gut Microbiota and Microbial Metabolism in Early Risk of Cardiometabolic Disease. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Curtis L Gabriel,Jane F Ferguson
Cardiometabolic disease comprises cardiovascular and metabolic dysfunction and underlies the leading causes of morbidity and mortality, both within the United States and worldwide. Commensal microbiota are implicated in the development of cardiometabolic disease. Evidence suggests that the microbiome is relatively variable during infancy and early childhood, becoming more fixed in later childhood and
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Molecular Biomarkers for Cardiometabolic Disease: Risk Assessment in Young Individuals. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Usman A Tahir,Robert E Gerszten
Cardiometabolic diseases, including cardiovascular disease and diabetes, are major causes of morbidity and mortality worldwide. Despite progress in prevention and treatment, recent trends show a stalling in the reduction of cardiovascular disease morbidity and mortality, paralleled by increasing rates of cardiometabolic disease risk factors in young adults, underscoring the importance of risk assessments
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Epigenetics of Early Cardiometabolic Disease: Mechanisms and Precision Medicine. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Andrea A Baccarelli,José Ordovás
Epigenetics has transformed our understanding of the molecular basis of complex diseases, including cardiovascular and metabolic disorders. This review offers a comprehensive overview of the current state of knowledge on epigenetic processes implicated in cardiovascular and metabolic diseases, highlighting the potential of DNA methylation as a precision medicine biomarker and examining the impact of
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Air Pollution, Built Environment, and Early Cardiovascular Disease. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Kai Zhang,Robert D Brook,Yuanfei Li,Sanjay Rajagopalan,Juyong Brian Kim
As the world's population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related
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Pregnancy as an Early Cardiovascular Moment: Peripartum Cardiovascular Health. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Sadiya S Khan,Natalie A Cameron,Kathryn J Lindley
Pregnancy is commonly referred to as a window into future CVH (cardiovascular health). During pregnancy, physiological adaptations occur to promote the optimal growth and development of the fetus. However, in approximately 20% of pregnant individuals, these perturbations result in cardiovascular and metabolic complications, which include hypertensive disorders of pregnancy, gestational diabetes, preterm
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Introduction to the Compendium on Early Cardiovascular Disease. Circ. Res. (IF 20.1) Pub Date : 2023-06-08 Matthew Nayor,Donald M Lloyd-Jones,Ravi V Shah
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An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis. Circ. Res. (IF 20.1) Pub Date : 2023-06-02 Jun-Ichi Abe,Masaki Imanishi,Shengyu Li,Aijun Zhang,Kyung Ae Ko,Venkata S K Samanthapudi,Ling-Ling Lee,Angelica Paniagua Bojorges,Young Jin Gi,Brian P Hobbs,Anita Deswal,Joerg Herrmann,Steven H Lin,Eduardo N Chini,Ying H Shen,Keri L Schadler,Thi-Hong-Minh Nguyen,Anisha A Gupte,Cielito Reyes-Gibby,Sai-Ching J Yeung,Rei J Abe,Elizabeth A Olmsted-Davis,Sunil Krishnan,Robert Dantzer,Nicolas L Palaskas
BACKGROUND ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and
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Missense Mutation in Human CHD4 Causes Ventricular Noncompaction by Repressing ADAMTS1. Circ. Res. (IF 20.1) Pub Date : 2023-05-31 Wei Shi,Angel P Scialdone,James I Emerson,Liu Mei,Lauren K Wasson,Haley A Davies,Christine E Seidman,Jonathan G Seidman,Jeanette G Cook,Frank L Conlon
BACKGROUND Left ventricular noncompaction (LVNC) is a prevalent cardiomyopathy associated with excessive trabeculation and thin compact myocardium. Patients with LVNC are vulnerable to cardiac dysfunction and at high risk of sudden death. Although sporadic and inherited mutations in cardiac genes are implicated in LVNC, understanding of the mechanisms responsible for human LVNC is limited. METHODS
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Spatial Multiplexed Protein Profiling of Cardiac Ischemia-Reperfusion Injury. Circ. Res. (IF 20.1) Pub Date : 2023-05-30 Luyan Yao,Funan He,Quanyi Zhao,Dandan Li,Shufang Fu,Mingzhi Zhang,Xingzhong Zhang,Bingying Zhou,Li Wang
BACKGROUND Reperfusion therapy is critical to myocardial salvage in the event of a myocardial infarction but is complicated by ischemia-reperfusion injury (IRI). Limited understanding of the spatial organization of cardiac cells, which governs cellular interaction and function, has hindered the search for targeted interventions minimizing the deleterious effects of IRI. METHODS We used imaging mass
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PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth. Circ. Res. (IF 20.1) Pub Date : 2023-05-26 Si Chen,Jiawei Chen,Wenting Du,Deanne M Mickelsen,Hangchuan Shi,Han Yu,Sparsh Kumar,Chen Yan
BACKGROUND Cyclic nucleotides play critical roles in cardiovascular biology and disease. PDE10A (phosphodiesterase 10A) is able to hydrolyze both cAMP and cGMP. PDE10A expression is induced in various human tumor cell lines, and PDE10A inhibition suppresses tumor cell growth. Chemotherapy drug such as doxorubicin (DOX) is widely used in chemotherapy. However, cardiotoxicity of DOX remains to be a serious
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LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts. Circ. Res. (IF 20.1) Pub Date : 2023-05-26 Chi-Ting Su,Daniel H W See,Yue-Jhu Huang,Tzu-Ming Jao,Shin-Yun Liu,Chih-Yi Chou,Chun-Fu Lai,Wei-Chou Lin,Chih-Yuan Wang,Jenq-Wen Huang,Kuan-Yu Hung
BACKGROUND As a part of natural disease progression, acute kidney injury (AKI) can develop into chronic kidney disease via renal fibrosis and inflammation. LTBP4 (latent transforming growth factor beta binding protein 4) regulates transforming growth factor beta, which plays a role in renal fibrosis pathogenesis. We previously investigated the role of LTBP4 in chronic kidney disease. Here, we examined
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Distinct Roles of DRP1 in Conventional and Alternative Mitophagy in Obesity Cardiomyopathy. Circ. Res. (IF 20.1) Pub Date : 2023-05-26 Mingming Tong,Risa Mukai,Satvik Mareedu,Peiyong Zhai,Shin-Ichi Oka,Chun-Yang Huang,Chiao-Po Hsu,Fawad A K Yousufzai,Luke Fritzky,Wataru Mizushima,Gopal J Babu,Junichi Sadoshima
BACKGROUND Obesity induces cardiomyopathy characterized by hypertrophy and diastolic dysfunction. Whereas mitophagy mediated through an Atg7 (autophagy related 7)-dependent mechanism serves as an essential mechanism to maintain mitochondrial quality during the initial development of obesity cardiomyopathy, Rab9 (Ras-related protein Rab-9A)-dependent alternative mitophagy takes over the role during
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Rebalancing Cardiac Structure and Function With Synthetic Mitochondria-Endoplasmic Reticulum Tethers. Circ. Res. (IF 20.1) Pub Date : 2023-05-25 Prasanna Katti,Brian Glancy
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UnWNTing the Heart: Targeting WNT Signaling in Pulmonary Arterial Hypertension. Circ. Res. (IF 20.1) Pub Date : 2023-05-25 Elena A Goncharova,Tatiana V Kudryashova,Vinicio A de Jesus Perez,Olga Rafikova
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Inflammasomes and Atherosclerosis: a Mixed Picture. Circ. Res. (IF 20.1) Pub Date : 2023-05-25 Alan R Tall,Karin E Bornfeldt
The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) and colchicine trials suggest an important role of inflammasomes and their major product IL-1β (interleukin 1β) in human atherosclerotic cardiovascular disease. Moreover, studies in mouse models indicate a causal role of inflammasomes and IL-1β in atherosclerosis. However, recent studies have led to a more granular view of the role
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Tumor Cell EnVoys Advance the Education of Platelets. Circ. Res. (IF 20.1) Pub Date : 2023-05-25 James I Hearn,Elizabeth E Gardiner
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HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy. Circ. Res. (IF 20.1) Pub Date : 2023-05-25 MacRae F Linton,Patricia G Yancey,Huan Tao,Sean S Davies
Epidemiologic studies detected an inverse relationship between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major risk factor for ASCVD and suggesting atheroprotective functions of HDL. However, the role of HDL-C as a mediator of risk for ASCVD has been called into question by the failure of HDL-C-raising drugs
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Multiomics Analyses of Peripheral Artery Disease Muscle Biopsies. Circ. Res. (IF 20.1) Pub Date : 2023-05-25 Ishita Jain,Beu P Oropeza,Ngan F Huang
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Correction to: LncRNA PSR Regulates Vascular Remodeling Through Encoding a Novel Protein Arteridin. Circ. Res. (IF 20.1) Pub Date : 2023-05-23
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A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Tamanna K Singh,David A Zidar,Keith McCrae,Kristin B Highland,Kristin Englund,Scott J Cameron,Mina K Chung
COVID-19 has become the first modern-day pandemic of historic proportion, affecting >600 million individuals worldwide and causing >6.5 million deaths. While acute infection has had devastating consequences, postacute sequelae of SARS-CoV-2 infection appears to be a pandemic of its own, impacting up to one-third of survivors and often causing symptoms suggestive of cardiovascular phenomena. This review
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Cell-Specific Mechanisms in the Heart of COVID-19 Patients. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Emily J Tsai,Daniela Cˇiháková,Nathan R Tucker
From the onset of the pandemic, evidence of cardiac involvement in acute COVID-19 abounded. Cardiac presentations ranged from arrhythmias to ischemia, myopericarditis/myocarditis, ventricular dysfunction to acute heart failure, and even cardiogenic shock. Elevated serum cardiac troponin levels were prevalent among hospitalized patients with COVID-19; the higher the magnitude of troponin elevation,
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COVID-19 and the Cardiovascular System: Requiem for a Medical Minotaur. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Milka Koupenova,Mina K Chung,Michael R Bristow
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Platelets and SARS-CoV-2 During COVID-19: Immunity, Thrombosis, and Beyond. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Anthony Sciaudone,Heather Corkrey,Fiachra Humphries,Milka Koupenova
COVID-19 is characterized by dysregulated thrombosis and coagulation that can increase mortality in patients. Platelets are fast responders to pathogen presence, alerting the surrounding immune cells and contributing to thrombosis and intravascular coagulation. The SARS-CoV-2 genome has been found in platelets from patients with COVID-19, and its coverage varies according to the method of detection
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Interaction of COVID-19 With Common Cardiovascular Disorders. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Peter K Boulos,Scott V Freeman,Timothy D Henry,Ehtisham Mahmud,John C Messenger
The onset and widespread dissemination of the severe acute respiratory syndrome coronavirus-2 in late 2019 impacted the world in a way not seen since the 1918 H1N1 pandemic, colloquially known as the Spanish Flu. Much like the Spanish Flu, which was observed to disproportionately impact young adults, it became clear in the early days of the coronavirus disease 2019 (COVID-19) pandemic that certain
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Repurposing Drugs for the Treatment of COVID-19 and Its Cardiovascular Manifestations. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Rui-Sheng Wang,Joseph Loscalzo
COVID-19 is an infectious disease caused by SARS-CoV-2 leading to the ongoing global pandemic. Infected patients developed a range of respiratory symptoms, including respiratory failure, as well as other extrapulmonary complications. Multiple comorbidities, including hypertension, diabetes, cardiovascular diseases, and chronic kidney diseases, are associated with the severity and increased mortality
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Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Mark C Chappell
The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection
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Microfluidic Organ-Chips and Stem Cell Models in the Fight Against COVID-19. Circ. Res. (IF 20.1) Pub Date : 2023-05-11 Sandro Satta,Sarah J Rockwood,Kaidong Wang,Shaolei Wang,Maedeh Mozneb,Madelyn Arzt,Tzung K Hsiai,Arun Sharma
SARS-CoV-2, the virus underlying COVID-19, has now been recognized to cause multiorgan disease with a systemic effect on the host. To effectively combat SARS-CoV-2 and the subsequent development of COVID-19, it is critical to detect, monitor, and model viral pathogenesis. In this review, we discuss recent advancements in microfluidics, organ-on-a-chip, and human stem cell-derived models to study SARS-CoV-2
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Critical Role of the cGAS-STING Pathway in Doxorubicin-Induced Cardiotoxicity. Circ. Res. (IF 20.1) Pub Date : 2023-05-08 Wei Luo,Xiaoyi Zou,Yidan Wang,Zheng Dong,Xinyu Weng,Zhiqiang Pei,Shuai Song,Yongchao Zhao,Zilun Wei,Rifeng Gao,Beijian Zhang,Liwei Liu,Peiyuan Bai,Jin Liu,Xiang Wang,Tingwen Gao,Yang Zhang,Xiaolei Sun,Hang Chen,Kai Hu,Shisuo Du,Aijun Sun,Junbo Ge
BACKGROUND Doxorubicin is an effective chemotherapy drug for treating various types of cancer. However, lethal cardiotoxicity severely limits its clinical use. Recent evidence has indicated that aberrant activation of the cytosolic DNA-sensing cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING (stimulator of interferon genes) pathway plays a critical role in cardiovascular
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Transcriptomic and Proteomic of Gastrocnemius Muscle in Peripheral Artery Disease. Circ. Res. (IF 20.1) Pub Date : 2023-05-08 Luigi Ferrucci,Julián Candia,Ceereena Ubaida-Mohien,Alexey Lyashkov,Nirad Banskota,Christiaan Leeuwenburgh,Stephanie Wohlgemuth,Jack M Guralnik,Mary Kaileh,Dongxue Zhang,Robert Sufit,Supriyo De,Myriam Gorospe,Rachel Munk,Charlotte A Peterson,Mary M McDermott
BACKGROUND Few effective therapies exist to improve lower extremity muscle pathology and mobility loss due to peripheral artery disease (PAD), in part because mechanisms associated with functional impairment remain unclear. METHODS To better understand mechanisms of muscle impairment in PAD, we performed in-depth transcriptomic and proteomic analyses on gastrocnemius muscle biopsies from 31 PAD participants
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Downregulation of FKBP5 Promotes Atrial Arrhythmogenesis. Circ. Res. (IF 20.1) Pub Date : 2023-05-08 Xiaolei Wang,Jia Song,Yue Yuan,Luge Li,Issam Abu-Taha,Jordi Heijman,Liang Sun,Shokoufeh Dobrev,Markus Kamler,Liang Xie,Xander H T Wehrens,Frank T Horrigan,Dobromir Dobrev,Na Li
BACKGROUND Atrial fibrillation (AF), the most common arrhythmia, is associated with the downregulation of FKBP5 (encoding FKBP5 [FK506 binding protein 5]). However, the function of FKBP5 in the heart remains unknown. Here, we elucidate the consequences of cardiomyocyte-restricted loss of FKBP5 on cardiac function and AF development and study the underlying mechanisms. METHODS Right atrial samples from
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Mechanism of Tumor-Platelet Communications in Cancer. Circ. Res. (IF 20.1) Pub Date : 2023-05-05 Tejasvi Dudiki,Manoj Veleeparambil,Irina Zhevlakova,Sudipta Biswas,Eric A Klein,Peter Ford,Eugene A Podrez,Tatiana V Byzova
BACKGROUND Thrombosis is one of the main complications in cancer patients often leading to mortality. However, the mechanisms underlying platelet hyperactivation are poorly understood. METHODS Murine and human platelets were isolated and treated with small extracellular vesicles (sEVs) from various cancer cell lines. The effects of these cancer-sEVs on platelets were evaluated both in vitro and in
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Role of Dickkopf-3 in Blood Pressure Regulation in Mice and Hypertensive Rats. Circ. Res. (IF 20.1) Pub Date : 2023-05-05 Carla Letizia Busceti,Albino Carrizzo,Franca Bianchi,Massimiliano De Lucia,Antonio Damato,Chiara Cazzin,Eleonora Venturini,Paola Di Pietro,Roxana Paula Ginerete,Luisa Di Menna,Maria Cotugno,Rosita Stanzione,Simona Marchitti,Serena Migliarino,Michele Ciccarelli,Sebastiano Sciarretta,Valeria Bruno,Giuseppe Battaglia,Francesco Fornai,Massimo Volpe,Speranza Rubattu,Ferdinando Nicoletti,Carmine Vecchione
BACKGROUND Dkk3 (Dickkopf-3) is a secreted glycoprotein known for its proapoptotic and angiogenic activity. The role of Dkk3 in cardiovascular homeostasis is largely unknown. Remarkably, the Dkk3 gene maps within a chromosome segment linked to the hypertensive phenotype in spontaneously hypertensive rats (SHR). METHODS We used Dkk3-/- mice or stroke-resistant (sr) and stroke-prone (sp) SHR to examine
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BIN1, Myotubularin, and Dynamin-2 Coordinate T-Tubule Growth in Cardiomyocytes. Circ. Res. (IF 20.1) Pub Date : 2023-05-04 Harmonie Perdreau-Dahl,David B Lipsett,Michael Frisk,Fatemeh Kermani,Cathrine R Carlson,Andreas Brech,Xin Shen,Anna Bergan-Dahl,Yufeng Hou,Tomi Tuomainen,Pasi Tavi,Peter P Jones,Marianne Lunde,J Andrew Wasserstrom,Jocelyn Laporte,Nina D Ullrich,Geir Christensen,J Preben Morth,William E Louch
BACKGROUND Transverse tubules (t-tubules) form gradually in the developing heart, critically enabling maturation of cardiomyocyte Ca2+ homeostasis. The membrane bending and scaffolding protein BIN1 (bridging integrator 1) has been implicated in this process. However, it is unclear which of the various reported BIN1 isoforms are involved, and whether BIN1 function is regulated by its putative binding
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A Critical Role for ERO1α in Arterial Thrombosis and Ischemic Stroke. Circ. Res. (IF 20.1) Pub Date : 2023-05-03 Vishwanath Jha,Bei Xiong,Tripti Kumari,Gavriel Brown,Jinzhi Wang,Kyungho Kim,Jingu Lee,Nathan Asquith,John Gallagher,Lillian Asherman,Taylor Lambert,Yanyan Bai,Xiaoping Du,Jeong-Ki Min,Rajan Sah,Ali Javaheri,Babak Razani,Jin-Moo Lee,Joseph E Italiano,Jaehyung Cho
BACKGROUND Platelet adhesion and aggregation play a crucial role in arterial thrombosis and ischemic stroke. Here, we identify platelet ERO1α (endoplasmic reticulum oxidoreductase 1α) as a novel regulator of Ca2+ signaling and a potential pharmacological target for treating thrombotic diseases. METHODS Intravital microscopy, animal disease models, and a wide range of cell biological studies were utilized
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Intestinal Lymphatic Dysfunction in Kidney Disease. Circ. Res. (IF 20.1) Pub Date : 2023-04-27 Jianyong Zhong,Annet Kirabo,Hai-Chun Yang,Agnes B Fogo,Elaine L Shelton,Valentina Kon
Kidney disease is associated with adverse consequences in many organs beyond the kidney, including the heart, lungs, brain, and intestines. The kidney-intestinal cross talk involves intestinal epithelial damage, dysbiosis, and generation of uremic toxins. Recent studies reveal that kidney injury expands the intestinal lymphatics, increases lymphatic flow, and alters the composition of mesenteric lymph
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Clinical Potential of Adrenomedullin Signaling in the Cardiovascular System. Circ. Res. (IF 20.1) Pub Date : 2023-04-27 László Bálint,Nathan P Nelson-Maney,Yanna Tian,Stephen D Serafin,Kathleen M Caron
Numerous clinical studies have revealed the utility of circulating AM (adrenomedullin) or MR-proAM (mid-regional proAM 45-92) as an effective prognostic and diagnostic biomarker for a variety of cardiovascular-related pathophysiologies. Thus, there is strong supporting evidence encouraging the exploration of the AM-CLR (calcitonin receptor-like receptor) signaling pathway as a therapeutic target. This
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The Lymphatic Vasculature in Cardiac Development and Ischemic Heart Disease. Circ. Res. (IF 20.1) Pub Date : 2023-04-27 Xiaolei Liu,Guillermo Oliver
In recent years, the lymphatic system has received increasing attention due to the fast-growing number of findings about its diverse novel functional roles in health and disease. It is well documented that the lymphatic vasculature plays major roles in the maintenance of tissue-fluid balance, the immune response, and in lipid absorption. However, recent studies have identified an additional growing