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Cardiomyocyte PRL2 Promotes Cardiac Hypertrophy via Directly Dephosphorylating AMPKα2. Circ. Res. (IF 16.5) Pub Date : 2025-02-14 Xue Han,Qiaojuan Shi,Yu Tu,Jiajia Zhang,Mengyang Wang,Weiqi Li,Yanan Liu,Ruyi Zheng,Jiajia Wei,Shiju Ye,Yanmei Zhang,Bozhi Ye,Yi Wang,Huazhong Ying,Guang Liang
BACKGROUND Pathological cardiac hypertrophy can result in heart failure. Protein dephosphorylation plays a primary role in the mediation of various cellular processes in cardiomyocytes. Here, we investigated the effects of a protein tyrosine phosphatase, PRL2 (phosphatase of regenerative liver 2), on pathological cardiac hypertrophy. METHODS The PRL2 knockout mice were subjected to angiotensin II infusion
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Mineral Stress and Vascular Aging: Decoding the Epigenetic Connection to Slow the Clock. Circ. Res. (IF 16.5) Pub Date : 2025-02-13 Qian Li,Lifang Ye,Jeffrey J Hsu
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Fiber, Fatty Acids, and Blood Pressure: A Gut-Level Solution. Circ. Res. (IF 16.5) Pub Date : 2025-02-13 Mohd Mabood Khan,Annet Kirabo
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Deciphering Platelets: Are They Cells or an Evolved Form of Extracellular Vesicles? Circ. Res. (IF 16.5) Pub Date : 2025-02-13 Eric Boilard,Dylan Burger,Edit Buzas,Paolo Gresele,Kellie R Machlus,Nigel Mackman,Pia Siljander,Rienk Nieuwland
Platelets are abundant in blood, where they maintain the integrity of the vasculature. Megakaryocytes, the cells responsible for platelet genesis, produce membrane protrusions from which as many as 5000 anucleate platelets can be released into the bloodstream. Platelets lack genomic DNA but contain different molecules, such as RNA, as well as organelles transmitted from the parent megakaryocyte. There
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SMC Abca1 and Abcg1 Deficiency Enhances Urinary Bladder Distension but Not Atherosclerosis. Circ. Res. (IF 16.5) Pub Date : 2025-02-11 Benedek Halmos,Anouk M La Rose,Daisey Methorst,Anouk G Groenen,Dalibor Nakládal,Venetia Bazioti,Mirjam H Koster,Niels J Kloosterhuis,Azuwerus van Buiten,Elisabeth M Schouten,Nicolette C A Huijkman,Miriam Langelaar-Makkinje,Laura Bongiovanni,Simon M De Neck,Alain de Bruin,Hendrik Buikema,Leo E Deelman,Marius C van den Heuvel,Folkert Kuipers,Igle Jan de Jong,Judith C Sluimer,Helle F Jørgensen,Robert
BACKGROUND Smooth muscle cells (SMCs) regulate blood flow distribution via vasoconstriction mediated by α-ARs (α-adrenergic receptors). Plasma membrane cholesterol accumulation affects α1-AR signaling and promotes loss of SMC contractile markers in vitro. ABCA1 and ABCG1 (ATP-binding cassette transporter A1 and G1) mediate cholesterol efflux to HDL (high-density lipoprotein). ABCA1/ABCG1 show high
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Novel Therapeutic Approach Targeting CXCR3 to Treat Immunotherapy Myocarditis. Circ. Res. (IF 16.5) Pub Date : 2025-02-11 Yuhsin Vivian Huang,Yin Sun,Harrison Chou,Noah Wagner,Maria Rosaria Vitale,Abraham L Bayer,Bruce Xu,Daniel Lee,Zachary Lin,Corynn Branche,Sarah Waliany,Joel W Neal,Heather A Wakelee,Ronald M Witteles,Patricia K Nguyen,Edward E Graves,Gerald J Berry,Pilar Alcaide,Sean M Wu,Han Zhu
BACKGROUND Immune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently limited. METHODS We used a genetic mouse model of PD1 deletion (MRL/Pdcd1-/-) along with a novel drug-treated ICI myocarditis
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Loss of Endothelial TRPC1 Induces Aortic Hypercontractility and Hypertension. Circ. Res. (IF 16.5) Pub Date : 2025-02-06 Yifei Zhu,Yuan Chu,Yihui Lan,Sheng Wang,Yizhi Zhang,Yuan Liu,Xianfeng Wang,Fan Yu,Xin Ma
BACKGROUND The increasing prevalence of obesity-related cardiovascular diseases demands a better understanding of the contribution of different cell types to vascular function for developing new treatment strategies. Previous studies have established a fundamental role of TRPC1 (transient receptor potential channel canonical family member 1) in blood vessels. However, little is known about its functional
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Preservation of Vascular Endothelial Function in Late-Onset Postmenopausal Women. Circ. Res. (IF 16.5) Pub Date : 2025-01-31 Sanna Darvish,Kevin O Murray,Katelyn R Ludwig,Krisha H Avalani,Daniel H Craighead,Kaitlin A Freeberg,Shaun Bevers,Julie A Reisz,Angelo D'Alessandro,Kerrie L Moreau,Douglas R Seals,Matthew J Rossman
BACKGROUND Postmenopausal women (PMW) who complete menopause at a late age (55+ years) have lower cardiovascular disease risk than PMW who complete menopause at a normal age (45-54 years). However, the influence of late-onset menopause on vascular endothelial dysfunction is unknown. Moreover, the mechanisms by which a later age at menopause may modulate endothelial function remain to be determined
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Micro RNA Regulating a Mega Difference in Male and Female Cardiac Physiology. Circ. Res. (IF 16.5) Pub Date : 2025-01-30 Wyatt G Paltzer,James F Martin
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Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential. Circ. Res. (IF 16.5) Pub Date : 2025-01-30 Zachary A Kohutek,Heather L Caslin,Daniel J Fehrenbach,J Brett Heimlich,Jonathan D Brown,Meena S Madhur,P Brent Ferrell,Amanda C Doran
Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating
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Placental Hypoxia-Induced Ferroptosis Drives Vascular Damage in Preeclampsia. Circ. Res. (IF 16.5) Pub Date : 2025-01-23 Chanho Park,Sruthi Alahari,Jonathan Ausman,Ruizhe Liu,Frederik Nguyen,Julien Sallais,Martin Post,Isabella Caniggia
BACKGROUND Iron is an essential micronutrient for cell survival and growth; however, excess of this metal drives ferroptosis. Although maternal iron imbalance and placental hypoxia are independent contributors to the pathogenesis of preeclampsia, a hypertensive disorder of pregnancy, the mechanisms by which their interaction impinge on maternal and placental health remain elusive. METHODS We used placentae
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NEDD4-Mediated GSNOR Degradation Aggravates Cardiac Hypertrophy and Dysfunction. Circ. Res. (IF 16.5) Pub Date : 2025-01-23 Xin Tang,Xiameng Liu,Xinqi Sha,Yan Zhang,Yan Zu,Qiyao Fan,Lulu Hu,Shixiu Sun,Zhiren Zhang,Feng Chen,ChengHui Yan,Xin Chen,Yueyue Xu,Wen Chen,Yongfeng Shao,Jiaxi Gu,Jun Pu,Bo Yu,Yaling Han,Liping Xie,Yi Han,Yong Ji
BACKGROUND The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the
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Gut Microbiota Metabolites Sensed by Host GPR41/43 Protect Against Hypertension. Circ. Res. (IF 16.5) Pub Date : 2025-01-22 Rikeish R Muralitharan,Tenghao Zheng,Evany Dinakis,Liang Xie,Anastasia Barbaro-Wahl,Hamdi A Jama,Michael Nakai,Madeleine Paterson,Kwan Charmaine Leung,Zoe McArdle,Katrina Mirabito Colafella,Chad Johnson,Wendy Qin,Ekaterina Salimova,Natalie J Bitto,Maria Kaparakis-Liaskos,David M Kaye,Joanne A O'Donnell,Charles R Mackay,Francine Z Marques
BACKGROUND Fermentation of dietary fiber by the gut microbiota leads to the production of metabolites called short-chain fatty acids, which lower blood pressure and exert cardioprotective effects. Short-chain fatty acids activate host signaling responses via the functionally redundant receptors GPR41 (G-protein-coupled receptor 41) and GPR43 (G-protein-coupled receptor 43), which are highly expressed
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Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification. Circ. Res. (IF 16.5) Pub Date : 2025-01-22 Chin Yee Ho,Meng-Ying Wu,Jirapath Thammaphet,Sadia Ahmad,James Ho C S,Lilia Draganova,Grace Anderson,Umesh S Jonnalagadda,Robert Hayward,Rukshana Shroff,Wilson Tan Lek Wen,Anja Verhulst,Roger Sy Foo,Catherine M Shanahan
BACKGROUND Vascular calcification is a detrimental aging pathology markedly accelerated in patients with chronic kidney disease. PLA (prelamin A) is a biomarker of vascular smooth muscle cell aging that accelerates calcification however the mechanisms remain undefined. METHODS Vascular smooth muscle cells were transduced with PLA using an adenoviral vector and epigenetic modifications were monitored
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TRIPLE Score: GPVI and CD36 Expression Predict a Prothrombotic Platelet Function Phenotype. Circ. Res. (IF 16.5) Pub Date : 2025-01-22 Alexander P Bye,Neline Kriek,Carly Kempster,Joanne L Dunster,Joanne L Mitchell,Tanya Sage,Suzannah Rawlings,Maria V Diaz Alonso,Valentina Shpakova,Abigail Whyte,Leanne Dymott,Sharon Mark,Mark Brunton,Joana Batista,Harriet McKinney,Patrick Thomas,Kate Downes,Amanda J Unsworth,Neil Ruparelia,Charlie McKenna,Chris I Jones,Jonathan M Gibbins
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Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease. Circ. Res. (IF 16.5) Pub Date : 2025-01-21 Rolando A Cuevas,Luis Hortells,Claire C Chu,Ryan Wong,Alex Crane,Camille K Boufford,Cailyn Regan,William J Moorhead,Michael J Bashline,Aneesha Parwal,Angelina M Parise,Parya Behzadi,Mark J Brown,Aditi U Gurkar,Dennis Bruemmer,John Sembrat,Ibrahim Sultan,Thomas G Gleason,Marie Billaud,Cynthia St Hilaire
BACKGROUND Calcific aortic valve disease is the pathological remodeling of valve leaflets. The initial steps in valve leaflet osteogenic reprogramming are not fully understood. As TERT (telomerase reverse transcriptase) overexpression primes mesenchymal stem cells to differentiate into osteoblasts, we investigated whether TERT contributes to the osteogenic reprogramming of valve interstitial cells
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Heart to Heal: Unveiling Follistatin's Potential for Myocardial Regeneration. Circ. Res. (IF 16.5) Pub Date : 2025-01-16 Alessia Costa,Christian Bär
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Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension. Circ. Res. (IF 16.5) Pub Date : 2025-01-16 Ashley L Mutchler,Alexandria Porcia Haynes,Mohammad Saleem,Sydney Jamison,Mohd Mabood Khan,Lale Ertuglu,Annet Kirabo
Access to excess dietary sodium has heightened the risk of cardiovascular diseases, particularly affecting individuals with salt sensitivity of blood pressure. Our research indicates that innate antigen-presenting immune cells contribute to rapid blood pressure increases in response to excess sodium intake. Emerging evidence suggests that epigenetic reprogramming, with subsequent transcriptional and
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Endothelial METAP1: Tipping the Angiogenic Scales in Postpartum Preeclampsia. Circ. Res. (IF 16.5) Pub Date : 2025-01-16 Jessica L Faulkner,Matthew R Alexander
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Targeting Endothelial Cell Mitochondrial Quality Control in PAH. Circ. Res. (IF 16.5) Pub Date : 2025-01-16 Mahin Gadkari,Karthik Suresh
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ABE-Mediated Cardiac Gene Silencing via Single AAVs Requires DNA Accessibility. Circ. Res. (IF 16.5) Pub Date : 2025-01-16 Zhanzhao Liu,Luzi Yang,Yuhan Yang,Jiting Li,Zhan Chen,Congting Guo,Qianhao Guo,Qiuxuan Li,Dongyu Zhao,Xiaomin Hu,Fei Gao,Yuxuan Guo
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Arterial NALCN Knockdown Ameliorates Mineralocorticoid-Induced Hypertension and Arterial Overcontractility. Circ. Res. (IF 16.5) Pub Date : 2025-01-10 Hyeryeong Lee,Solah Park,Dong Jun Sung,Jin Ryeol An,Mi Seon Seo,Hyun Ju Noh,Jueng Soo You,Sung Hea Kim,Hana Cho,Bokyung Kim,Sang Woong Park,Young Min Bae
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Vps4a Mediates a Unified Membrane Repair Machinery to Attenuate Ischemia/Reperfusion Injury. Circ. Res. (IF 16.5) Pub Date : 2025-01-07 Xiaozhi Huang,Jiayin Zhang,Chen Xu,Ranran Cao,Peijun Jiang,Xue Ji,Wenyi Wang,Zhishan Huang,Peidong Han
BACKGROUND Cardiac ischemia/reperfusion disrupts plasma membrane integrity and induces various types of programmed cell death. The ESCRT (endosomal sorting complex required for transport) proteins, particularly AAA-ATPase Vps4a (vacuolar protein sorting 4a), play an essential role in the surveillance of membrane integrity. However, the role of ESCRT proteins in the context of cardiac injury remains
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Stick to the Script: How Endomucin Keeps the Glycocalyx in Line. Circ. Res. (IF 16.5) Pub Date : 2025-01-02 Ronald McMillan,Benjamin Rodriguez,Annet Kirabo
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Targeting Cardiac Fibrosis With a Vaccine Against Fibroblast Activation Protein. Circ. Res. (IF 16.5) Pub Date : 2025-01-02 William M Oldham
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Cellular and Molecular Mechanisms Leading to Air Travel-Induced Thrombosis. Circ. Res. (IF 16.5) Pub Date : 2025-01-02 Julie Tourn,Lydie Crescence,Laurie Bruzzese,Laurence Panicot-Dubois,Christophe Dubois
Venous thromboembolism, characterized by deep vein thrombosis and pulmonary embolism, is the third cardiovascular disease in the world. Deep vein thrombosis occurs when a blood clot forms in areas of impaired blood flow, and it is significantly affected by environmental factors. Local hypoxia, caused by venous stasis, plays a critical role in deep vein thrombosis under normal conditions, and this effect
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Vascular-Adipose Crosstalk: Angiogenesis and Adipose Tissue Remodeling. Circ. Res. (IF 16.5) Pub Date : 2025-01-02 Timothy P Fitzgibbons,Sophia Kogan,Khanh-Van Tran
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Discovery of Titin and Its Role in Heart Function and Disease. Circ. Res. (IF 16.5) Pub Date : 2025-01-02 Henk L Granzier,Siegfried Labeit
This review examines the giant elastic protein titin and its critical roles in heart function, both in health and disease, as discovered since its identification nearly 50 years ago. Encoded by the TTN (titin gene), titin has emerged as a major disease locus for cardiac disorders. Functionally, titin acts as a third myofilament type, connecting sarcomeric Z-disks and M-bands, and regulating myocardial
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BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness. Circ. Res. (IF 16.5) Pub Date : 2025-01-01 Yanan Liu,Mengke Li,Zhipeng Chen,Min Zuo,Kaiwen Bao,Ziyan Zhao,Meng Yan,Yongping Bai,Ding Ai,Hu Wang,Hongfeng Jiang
BACKGROUND Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)-induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg2+/Mn2+-dependent 1B)-lysine 63(K63) deubiquitination. In this study, we aimed to elucidate the role
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X-Chromosome-Linked miRNAs Regulate Sex Differences in Cardiac Physiology. Circ. Res. (IF 16.5) Pub Date : 2024-12-30 James I Emerson,Wei Shi,Jose Paredes-Larios,William G Walker,Josiah E Hutton,Ileana M Cristea,William F Marzluff,Frank L Conlon
BACKGROUND Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states. METHODS We identified microRNAs (miRNAs/miR) with sex-differential expression in mouse hearts. RESULTS Four conserved miRNAs are present in a single locus on the X-chromosome and are expressed at higher levels in females than males. We show miRNA, miR-871
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Venous Endothelial Cell Transcriptomic Profiling Implicates METAP1 in Preeclampsia. Circ. Res. (IF 16.5) Pub Date : 2024-12-27 Maria A Pabon,Robert M Weisbrod,Claire Castro,Haobo Li,Peng Xia,Jiayi Kang,Maddalena Ardissino,Katherine E Economy,Zihui Yang,Yanxi Shi,Eunice Kim,Anna Perillo,Leanne Barrett,Jenifer M Brown,Sanjay Divakaran,Murat Cetinbas,Ruslan I Sadreyev,Antonio de Marvao,Malissa J Wood,Nandita S Scott,Emily S Lau,Jennifer E Ho,Marcelo F Di Carli,Jason D Roh,Naomi M Hamburg,Michael C Honigberg
BACKGROUND Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia. METHODS Venous ECs were isolated from postpartum patients
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Collagen Pyridinoline Cross-Links Are Absent in Reversible Myocardial Fibrosis. Circ. Res. (IF 16.5) Pub Date : 2024-12-24 Eman Akam-Baxter,Sterling J Ridley,Brianna F Moon,Peter Caravan,David E Sosnovik
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ACKR1hiECs Promote Aortic Dissection Through Adjusting Macrophage Behavior. Circ. Res. (IF 16.5) Pub Date : 2024-12-18 Yayu Wang,Xiong Jia,Yifei Zhang,Bin Zhang,Yazhe Zhou,Xiaoru Li,Xiaoying Zhu,Jinquan Xia,Jun Ren,Chang Zou,Qijun Zheng
BACKGROUND Type A aortic dissection (TAAD) is a life-threatening condition characterized by complex pathophysiology, in which macrophages play a critical but not yet fully understood role. This study focused on the role of endothelial cells with elevated expression of ACKR1 (atypical chemokine receptor 1) and their interaction with proinflammatory macrophages in TAAD development. METHODS Single-cell
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Follistatin From hiPSC-Cardiomyocytes Promotes Myocyte Proliferation in Pigs With Postinfarction LV Remodeling. Circ. Res. (IF 16.5) Pub Date : 2024-12-18 Yuhua Wei,Gregory Walcott,Thanh Nguyen,Xiaoxiao Geng,Bijay Guragain,Hanyu Zhang,Akazha Green,Manuel Rosa-Garrido,Jack M Rogers,Daniel J Garry,Lei Ye,Jianyi Zhang
BACKGROUND When human induced pluripotent stem cells (hiPSCs) that CCND2-OE (overexpressed cyclin-D2) were differentiated into cardiomyocytes (CCND2-OEhiPSC-CMs) and administered to the infarcted hearts of immunodeficient mice, the cells proliferated after administration and repopulated >50% of the scar. Here, we knocked out human leukocyte antigen class I and class II expression in CCND2-OEhiPSC-CMs
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SGLT2 Inhibition Induces Cardioprotection by Increasing Parasympathetic Activity. Circ. Res. (IF 16.5) Pub Date : 2024-12-17 Maryna V Basalay,Alla Korsak,Zhenhe He,Alexander V Gourine,Sean M Davidson,Derek M Yellon
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ET-3/ETBR Mediates Na+-Activated Immune Signaling and Kidney Lymphatic Dynamics. Circ. Res. (IF 16.5) Pub Date : 2024-12-16 Ashley L Mutchler,Jianyong Zhong,Hai-Chun Yang,Shilin Zhao,Rachelle Crescenzi,Shannon Taylor,Roy L Rao,Elaine L Shelton,Annet Kirabo,Valentina Kon
BACKGROUND Lymphatic collecting vessels in the kidney are critical in clearing interstitial fluid, macromolecules, and infiltrating immune cells. Dysfunction of the lymphatic vessels can disrupt this process and exacerbate injury-associated inflammation in many disease conditions. We previously found that sodium accumulates within the kidney interstitium during proteinuric kidney injury and elevated
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Endothelial FUNDC1 Deficiency Drives Pulmonary Hypertension. Circ. Res. (IF 16.5) Pub Date : 2024-12-10 Yandong Pei,Dongfeng Ren,Yuanhao Yin,Jiajia Shi,Qianyuan Ai,Wenxin Hao,Xiaofan Luo,Chenyue Zhang,Yanping Zhao,Chenyu Bai,Lin Zhu,Qiong Wang,Shuangling Li,Yuwei Zhang,Jiangtao Lu,Lin Liu,Lin Zhou,Yuli Wu,Yiqi Weng,Yongle Jing,Chengzhi Lu,Yujie Cui,Hao Zheng,Yanjun Li,Guo Chen,Gang Hu,Quan Chen,Xudong Liao
BACKGROUND Pulmonary hypertension (PH) is associated with endothelial dysfunction. However, the cause of endothelial dysfunction and its impact on PH remain incompletely understood. We aimed to investigate whether the hypoxia-inducible FUNDC1 (FUN14 domain-containing 1)-dependent mitophagy pathway underlies PH pathogenesis and progression. METHODS We first analyzed FUNDC1 protein levels in lung samples
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Salt's Sex-Specific Impact of Gut Microbiota in Hypertension. Circ. Res. (IF 16.5) Pub Date : 2024-12-05 Selam Desta,Claude F Albritton,Annet Kirabo
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Correction to: Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF. Circ. Res. (IF 16.5) Pub Date : 2024-12-05
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Transcription Factor 21 Regulates Cardiac Myofibroblast Formation and Fibrosis. Circ. Res. (IF 16.5) Pub Date : 2024-12-04 Anne Katrine Z Johansen,Rajesh K Kasam,Ronald J Vagnozzi,Suh-Chin J Lin,Jose Gomez-Arroyo,Adenike Shittu,Stephanie L K Bowers,Yasuhide Kuwabara,Kelly M Grimes,Kathrynne Warrick,Michelle A Sargent,Tanya A Baldwin,Susan E Quaggin,Artem Barski,Jeffery D Molkentin
BACKGROUND TCF21 (transcription factor 21) is a bHLH (basic helix-loop-helix) protein required for the developmental specification of cardiac fibroblasts (CFs) from epicardial progenitor cells that surround the embryonic heart. In the adult heart, TCF21 is expressed in tissue-resident fibroblasts and is downregulated in response to injury or stimuli leading to myofibroblast differentiation. These findings
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A Vaccine Against Fibroblast Activation Protein Improves Murine Cardiac Fibrosis by Preventing the Accumulation of Myofibroblasts. Circ. Res. (IF 16.5) Pub Date : 2024-12-04 Shota Yoshida,Hiroki Hayashi,Takuro Kawahara,Shunsuke Katsuki,Mitsukuni Kimura,Rissei Hino,Jiao Sun,Ryo Nakamaru,Akiko Tenma,Masayoshi Toyoura,Satoshi Baba,Munehisa Shimamura,Tomohiro Katsuya,Ryuichi Morishita,Hiromi Rakugi,Tetsuya Matoba,Hironori Nakagami
BACKGROUND Myofibroblasts are primary cells involved in chronic response-induced cardiac fibrosis. Fibroblast activation protein (FAP) is a relatively specific marker of activated myofibroblasts and a potential target molecule. This study aimed to clarify whether a vaccine targeting FAP could eliminate myofibroblasts in chronic cardiac stress model mice and reduce cardiac fibrosis. METHODS We coadministered
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Autoimmune-Like Mechanism in Heart Failure Enables Preventive Vaccine Therapy. Circ. Res. (IF 16.5) Pub Date : 2024-12-04 Elisa Martini,Marco Cremonesi,Arianna Felicetta,Simone Serio,Simone Puccio,Erica Pelamatti,Jasper J P van Beek,Vasiliki Papadopoulou,Chiara Catalano,Francesca Fanuele,Desirée Giuliano,Gianluca Basso,Cecilia Assunta Bonfiglio,Cristina Panico,Marco Vacchiano,Pierluigi Carullo,Laura Papa,Carla D'Andrea,Naz Tuzger,Sergio Marchini,Paola Magistroni,Silvia Deaglio,Antonio Amoroso,Enrico Lugli,Gianluigi Condorelli
BACKGROUND Heart failure (HF) is strongly associated with inflammation. In pressure overload (PO)-induced HF, cardiac stress triggers adaptive immunity, ablation or inhibition of which blocks disease progression. We hypothesized that PO-HF might fulfill the often-used criteria of autoimmunity: if so, the associated adaptive immune response would be not only necessary but also sufficient to induce HF;
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GSK3β Deficiency Expands Obese Adipose Vasculature to Mitigate Metabolic Disorders. Circ. Res. (IF 16.5) Pub Date : 2024-12-04 Li Wang,Jiajia Li,Ping Tang,Dongliang Zhu,Lixin Tai,Yuan Wang,Tsukiko Miyata,James R Woodgett,Li-Jun Di
BACKGROUND Maintaining a well-developed vascular system alongside adipose tissue (AT) expansion significantly reduces the risk of metabolic complications. Although GSK3β (glycogen synthase kinase-3 beta) is known for its role in various cellular processes, its specific functions in AT and regulation of body homeostasis have not been reported. METHODS GSK3β-floxed and GSK3α-floxed mice were crossed
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Social Bonds Retain Oxytocin-Mediated Brain-Liver Axis to Retard Atherosclerosis. Circ. Res. (IF 16.5) Pub Date : 2024-11-27 Seien Ko,Atsushi Anzai,Xueyuan Liu,Kenichiro Kinouchi,Kazuhiro Yamanoi,Takuto Torimitsu,Genki Ichihara,Hiroki Kitakata,Kohsuke Shirakawa,Yoshinori Katsumata,Jin Endo,Kaori Hayashi,Masahide Yoshida,Katsuhiko Nishimori,Kenji F Tanaka,Tatsushi Onaka,Motoaki Sano,Masaki Ieda
BACKGROUNDS Social interaction with others is essential to life. Although social isolation and loneliness have been implicated as increased risks of cardiometabolic and cardiovascular diseases and all-cause mortality, the cellular and molecular mechanisms by which social connection maintains cardiometabolic and cardiovascular health remain largely unresolved. METHODS To investigate how social connection
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Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment. Circ. Res. (IF 16.5) Pub Date : 2024-11-25 Zhengping Hu,Issahy Cano,Fengyang Lei,Jie Liu,Ramon Bossardi Ramos,Harper Gordon,Eleftherios I Paschalis,Magali Saint-Geniez,Yin Shan Eric Ng,Patricia A D'Amore
BACKGROUND EMCN (endomucin), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of VEGF (vascular endothelial growth factor) activity through modulating VEGFR2 (VEGF receptor 2) endocytosis. The goal of this study is to investigate the phenotypic
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ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm. Circ. Res. (IF 16.5) Pub Date : 2024-11-08 Hao Wu,Zhiqing Li,Liu Yang,Lin He,Hao Liu,Shiyu Yang,Qinfeng Xu,Yanjie Li,Wenqiang Li,Yiran Li,Ze Gong,Yicong Shen,Xueyuan Yang,Jiaqi Huang,Fang Yu,Li Li,Junming Zhu,Luyang Sun,Yi Fu,Wei Kong
BACKGROUND Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood. METHODS Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice. To investigate the
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Kindlin-2 Phase Separation in Response to Flow Controls Vascular Stability. Circ. Res. (IF 16.5) Pub Date : 2024-11-04 Nina Ma,Fangfang Wu,Jiayu Liu,Ziru Wu,Lu Wang,Bochuan Li,Yuming Liu,Xue Dong,Junhao Hu,Xi Fang,Heng Zhang,Ding Ai,Jing Zhou,Xiaohong Wang
BACKGROUND Atheroprotective shear stress preserves endothelial barrier function, while atheroprone shear stress enhances endothelial permeability. Yet, the underlying mechanisms through which distinct flow patterns regulate EC integrity remain to be clarified. This study aimed to investigate the involvement of Kindlin-2, a key component of focal adhesion and endothelial adherens junctions crucial for
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CAR-Macrophage Therapy Alleviates Myocardial Ischemia-Reperfusion Injury. Circ. Res. (IF 16.5) Pub Date : 2024-10-28 Jiawan Wang,Heng Du,Wanrun Xie,Jinmiao Bi,Hao Zhang,Xu Liu,Yuhan Wang,Shaolong Zhang,Anhua Lei,Chuting He,Hailong Yuan,Jiahe Zhang,Yujing Li,Pengfei Xu,Siqi Liu,Yanan Zhou,Jianghua Shen,Jingdong Wu,Yihong Cai,Chaofan Yang,Zeya Li,Yingxin Liang,Yang Zhao,Jin Zhang,Moshi Song
BACKGROUND Given the growing acknowledgment of the detrimental effects of excessive myocardial fibrosis on pathological remodeling after myocardial ischemia-reperfusion injury (I/R), targeting the modulation of myocardial fibrosis may offer protective and therapeutic advantages. However, effective clinical interventions and therapies that target myocardial fibrosis remain limited. As a promising chimeric
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HFpEF's Fuel Flaw: Impaired Fatty Acid Oxidation Stalls Mitophagy. Circ. Res. (IF 16.5) Pub Date : 2024-10-24 Xi Fang,Åsa B Gustafsson
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Salt-Responsive Gut Microbiota Induces Sex-Specific Blood Pressure Changes. Circ. Res. (IF 16.5) Pub Date : 2024-10-23 Pritam Bardhan,Xue Mei,Ngoc Khanh Lai,Blair Mell,Ramakumar Tummala,Sachin Aryal,Ishan Manandhar,Hyeongu Hwang,Tania Akter Jhuma,Rohit Reddy Atluri,Jun Kyoung,Ying Li,Bina Joe,Hong-Bao Li,Tao Yang
BACKGROUND Tryptophan metabolism is important in blood pressure regulation. The tryptophan-indole pathway is exclusively mediated by the gut microbiota. ACE2 (angiotensin-converting enzyme 2) participates in tryptophan absorption, and a lack of ACE2 leads to changes in the gut microbiota. The gut microbiota has been recognized as a regulator of blood pressure. Furthermore, there is ample evidence for
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Cytotoxic T Cells Drive Outcome in Inflammatory Dilated Cardiomyopathy. Circ. Res. (IF 16.5) Pub Date : 2024-10-21 Maurits A Sikking,Daniel Harding,Michiel T H M Henkens,Sophie L V M Stroeks,Max F G H M Venner,Bastien Nihant,Rick E W van Leeuwen,Silvia Fanti,Xiaofei Li,Pieter van Paassen,Christian Knackstedt,Hans-Peter Brunner-la Rocca,Vanessa P M van Empel,Job A J Verdonschot,Federica M Marelli-Berg,Stephane R B Heymans
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Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation. Circ. Res. (IF 16.5) Pub Date : 2024-10-18 Johannes Zeller,Julia Loseff-Silver,Khashayar Khoshmanesh,Sara Baratchi,Austin Lai,Tracy L Nero,Abhishek Roy,Anna Watson,Nalin Dayawansa,Prerna Sharma,Anastasia Barbaro-Wahl,Yung Chih Chen,Mitchell Moon,Mark Louis P Vidallon,Angela Huang,Julia Thome,Karen S Cheung Tung Shing,Dalton Harvie,Marie N Bongiovanni,David Braig,Craig J Morton,Nay M Htun,Dion Stub,Anthony Walton,John Horowitz,Xiaowei Wang,Geoffrey
BACKGROUND CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand
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Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP. Circ. Res. (IF 16.5) Pub Date : 2024-10-18 Minjun Kang,Choon-Soo Lee,HyunJu Son,Jeongha Lee,Jaewon Lee,Hyun Ju Seo,Moo-Kang Kim,Murim Choi,Hyun-Jai Cho,Hyo-Soo Kim
BACKGROUND Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear. METHODS The embryonic lethality resulting from Lphn2 deletion necessitates
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Ferroptosis-Mediated Inflammation Promotes Pulmonary Hypertension. Circ. Res. (IF 16.5) Pub Date : 2024-10-18 Felipe Kazmirczak,Neal T Vogel,Sasha Z Prisco,Michael T Patterson,Jeffrey Annis,Ryan T Moon,Lynn M Hartweck,Jenna B Mendelson,Minwoo Kim,Natalia Calixto Mancipe,Todd Markowski,LeeAnn Higgins,Candace Guerrero,Ben Kremer,Madelyn L Blake,Christopher J Rhodes,Jesse W Williams,Evan L Brittain,Kurt W Prins
BACKGROUND Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that
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EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis. Circ. Res. (IF 16.5) Pub Date : 2024-10-18 Di Chen,Yipei Tang,Philip E Lapinski,David Wiggins,Eva M Sevick,Michael J Davis,Philip D King
BACKGROUND EPHB4 (ephrin receptor B4) and the RASA1 (p120 Ras GTPase-activating protein) are necessary for the development of lymphatic vessel (LV) valves. However, precisely how EPHB4 and RASA1 regulate LV valve development is unknown. In this study, we examine the mechanisms by which EPHB4 and RASA1 regulate the development of LV valves. METHODS We used LV-specific inducible EPHB4-deficient mice
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Salt and CHIP: Tet2-CH Aggravates Salt-Sensitive Hypertension in Mice. Circ. Res. (IF 16.5) Pub Date : 2024-10-10 Caitlyn Vlasschaert,Steven D Crowley,Alexander G Bick
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Cell-Free RNA Signatures in Maternal Blood with Fetal Congenital Heart Disease. Circ. Res. (IF 16.5) Pub Date : 2024-10-02 Matthew Alonzo,Zhaohui Xu,Yang Yu,Shiqiao Ye,Cankun Wang,Jerry Wang,Megan McNutt,Jakob Bering,Qin Ma,Karen Texter,Vidu Garg,Ming-Tao Zhao
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LRP1 Repression by SNAIL Results in ECM Remodeling in Genetic Risk for Vascular Diseases. Circ. Res. (IF 16.5) Pub Date : 2024-10-02 Lu Liu,Joséphine Henry,Yingwei Liu,Charlène Jouve,Jean-Sébastien Hulot,Adrien Georges,Nabila Bouatia-Naji
BACKGROUND Genome-wide association studies implicate common genetic variations in the LRP1 (low-density lipoprotein receptor-related protein 1 gene) locus at risk for multiple vascular diseases and traits. However, the underlying biological mechanisms are unknown. METHODS Fine mapping analyses included Bayesian colocalization to identify the most likely causal variant. Human induced pluripotent stem
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Transformation of the Kidney into a Pathological Neuro-Immune-Endocrine Organ. Circ. Res. (IF 16.5) Pub Date : 2024-10-01 Manako Yamaguchi,Lucas Ferreira de Almeida,Hiroki Yamaguchi,Xiuyin Liang,Jason P Smith,Silvia Medrano,Maria Luisa S Sequeira-Lopez,R Ariel Gomez
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Blunted Cardiac Mitophagy in Response to Metabolic Stress Contributes to HFpEF. Circ. Res. (IF 16.5) Pub Date : 2024-09-27 Akira Yoshii,Timothy S McMillen,Yajun Wang,Bo Zhou,Hongye Chen,Durba Banerjee,Melisa Herrero,Pei Wang,Naoto Muraoka,Wang Wang,Charles E Murry,Rong Tian
BACKGROUND Metabolic remodeling and mitochondrial dysfunction are hallmarks of heart failure with reduced ejection fraction. However, their role in the pathogenesis of HF with preserved ejection fraction (HFpEF) is poorly understood. METHODS In a mouse model of HFpEF, induced by high-fat diet and Nω-nitrol-arginine methyl ester, cardiac energetics was measured by 31P nuclear magnetic resonance (NMR)