-
Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation Circ. Res. (IF 20.1) Pub Date : 2024-04-17 Wenqi Ma, Kangni Jia, Haomai Cheng, Hong Xu, Zhigang Li, Hang Zhang, Hongyang Xie, Lingfang Zhuang, Ziyang Wang, Yuke Cui, Hang Sun, Lei Yi, Zhiyong Chen, Shengzhong Duan, Motoaki Sano, Keiichi Fukuda, Lin Lu, Fei Gao, Ruiyan Zhang, Xiaoxiang Yan
BACKGROUND:Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression;
-
Immunoproteasomal Processing of IsoLG-Adducted Proteins Is Essential for Hypertension Circ. Res. (IF 20.1) Pub Date : 2024-04-16 Néstor de la Visitación, Wei Chen, Jaya Krishnan, Justin P. Van Beusecum, Venkataraman Amarnath, Elizabeth M. Hennen, Shilin Zhao, Mohammad Saleem, Mingfang Ao, Sergey I. Dikalov, Anna E. Dikalova, David G. Harrison, David M. Patrick
BACKGROUND:Hypertension is characterized by CD8+ T cell activation and infiltration into peripheral tissues. CD8+ T cell activation requires proteasomal processing of antigenic proteins. It has become clear that isoLG (isolevuglandin)-adduced peptides are antigenic in hypertension; however, IsoLGs inhibit the constitutive proteasome. We hypothesized that immunoproteasomal processing of isoLG-adducts
-
Buffering Mechanism in Aortic Arch Artery Formation and Congenital Heart Disease Circ. Res. (IF 20.1) Pub Date : 2024-04-15 AnnJosette Ramirez, Christina A. Vyzas, Huaning Zhao, Kevin Eng, Karl Degenhardt, Sophie Astrof
BACKGROUND:The resiliency of embryonic development to genetic and environmental perturbations has been long appreciated; however, little is known about the mechanisms underlying the robustness of developmental processes. Aberrations resulting in neonatal lethality are exemplified by congenital heart disease arising from defective morphogenesis of pharyngeal arch arteries (PAAs) and their derivatives
-
Inhibition of the mPTP and Lipid Peroxidation Is Additively Protective Against I/R Injury Circ. Res. (IF 20.1) Pub Date : 2024-04-15 Arielys Mendoza, Pooja Patel, Dexter Robichaux, Daniel Ramirez, Jason Karch
BACKGROUND:During myocardial ischemia/reperfusion (I/R) injury, high levels of matrix Ca2+ and reactive oxygen species (ROS) induce the opening of the mitochondrial permeability transition pore (mPTP), which causes mitochondrial dysfunction and ultimately necrotic death. However, the mechanisms of how these triggers individually or cooperatively open the pore have yet to be determined.METHODS:Here
-
Meet the First Authors Circ. Res. (IF 20.1) Pub Date : 2024-04-11
Dr Kajsa Arkelius completed her Ph.D. in Experimental Vascular Research from the Applied Neurovascular Research group at the University of Lund, Sweden, under the guidance of Dr Saema Ansar. Her doctoral research primarily focused on developing innovative therapeutic approaches to enhance thrombolysis therapy following ischemic stroke. Currently, Dr Arkelius is a postdoctoral fellow in Neurology at
-
Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions Circ. Res. (IF 20.1) Pub Date : 2024-04-11 Sojin Youn Wass, Omar Hahad, Zain Asad, Shuo Li, Mina K. Chung, Emelia J. Benjamin, Khurram Nasir, Sanjay Rajagopalan, Sadeer G. Al-Kindi
There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression
-
Correction to: Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery Circ. Res. (IF 20.1) Pub Date : 2024-04-11
In the article by Kim et al, “Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery,” which published in the March 15, 2024 issue of the journal (Circ Res. 2023;134:727-747. doi: 10.1161/CIRCRESAHA.123.323521), a correction was needed. There is an error in Figure 3 where the descriptions of the solid line and the dotted line are inaccurate and have therefore been removed from the figure footnote
-
In This Issue Circ. Res. (IF 20.1) Pub Date : 2024-04-11
Eliminating the blood clot responsible for an ischemic stroke can improve a patient’s outcome, even save their life. But, the treatment—an intravenous dose of tissue plasminogen activator (rt-PA)—can only be given in the first few hours of symptoms. After that, the risk of hemorrhage associated with rt-PA is no longer offset by its benefits. Increased matrix metalloprotease 9 (MMP-9), which breaks
-
Orphan GPCR GPRC5C Facilitates Angiotensin II-Induced Smooth Muscle Contraction Circ. Res. (IF 20.1) Pub Date : 2024-04-10 Tianpeng Wang, Jingchen Shao, Shamit Kumar, Mohammad Wessam Alnouri, Jorge Carvalho, Stefan Günther, Cornelius Krasel, Kate T. Murphy, Moritz Bünemann, Stefan Offermanns, Nina Wettschureck
BACKGROUND:GPCRs (G-protein-coupled receptors) play a central role in the regulation of smooth muscle cell (SMC) contractility, but the function of SMC-expressed orphan GPCR class C group 5 member C (GPRC5C) is unclear.OBJECTIVE:The aim of this project is to define the role of GPRC5C in SMC in vitro and in vivo.METHODS AND RESULTS:We studied the role of GPRC5C in the regulation of SMC contractility
-
Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis Circ. Res. (IF 20.1) Pub Date : 2024-04-02 Anita Tamiato, Lukas S. Tombor, Ariane Fischer, Marion Muhly-Reinholz, Leah Rebecca Vanicek, Büşra Nur Toğru, Jessica Neitz, Simone Franziska Glaser, Maximilian Merten, David Rodriguez Morales, Jeonghyeon Kwon, Stephan Klatt, Bianca Schumacher, Stefan Günther, Wesley T. Abplanalp, David John, Ingrid Fleming, Nina Wettschureck, Stefanie Dimmeler, Guillermo Luxán
BACKGROUND:Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown.METHODS:In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes
-
Endothelial PTP1B Deletion Promotes VWF Exocytosis and Venous Thromboinflammation Circ. Res. (IF 20.1) Pub Date : 2024-04-02 Konstantinos Zifkos, Magdalena L. Bochenek, Rajinikanth Gogiraju, Stephane Robert, Denise Pedrosa, Klytaimnistra Kiouptsi, Kateryna Moiko, Mathias Wagner, Felix Mahfoud, Philippe Poncelet, Thomas Münzel, Wolfram Ruf, Christoph Reinhardt, Laurence Panicot-Dubois, Christophe Dubois, Katrin Schäfer
BACKGROUND:Endothelial activation promotes the release of procoagulant extracellular vesicles and inflammatory mediators from specialized storage granules. Endothelial membrane exocytosis is controlled by phosphorylation. We hypothesized that the absence of PTP1B (protein tyrosine phosphatase 1B) in endothelial cells promotes venous thromboinflammation by triggering endothelial membrane fusion and
-
CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation Circ. Res. (IF 20.1) Pub Date : 2024-04-01 Junxiong Chen, Yingjun Ding, Chao Jiang, Rongmei Qu, Jonathan D. Wren, Constantin Georgescu, Xuejun Wang, Darlene N. Reuter, Beibei Liu, Cory B. Giles, Christoph H. Mayr, Herbert B. Schiller, Jingxing Dai, Christopher S. Stipp, Bharathiraja Subramaniyan, Jie Wang, Houjuan Zuo, Chao Huang, Kar-Ming Fung, Heather C. Rice, Arnoud Sonnenberg, David Wu, Matthew S. Walters, You-Yang Zhao, Tomoharu Kanie
BACKGROUND:Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown.METHODS:In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related
-
In This Issue Circ. Res. (IF 20.1) Pub Date : 2024-03-28
A high-fiber diet is believed to reduce a person’s likelihood of developing type 2 diabetes, but it isn’t clear how. Since dietary fiber is not digested by human enzymes, Wang and colleagues hypothesized that fiber-eating gut microbes might be involved. To find out, the team examined diet data, fecal microbiomes, serum metabolites and markers of diabetes in thousands of participants. The analyses revealed
-
Meet the First Authors Circ. Res. (IF 20.1) Pub Date : 2024-03-28
Dr Zheng Wang is a Research Assistant Professor in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine, Bronx, New York. Dr Wang earned his PhD in microbiology from The Chinese University of Hong Kong. He completed his postdoctoral training in Microbiome and Microbial Genomics at Columbia University Medical Center. His research has focused on human microbiome
-
Biological Pacemakers: Present and Future Circ. Res. (IF 20.1) Pub Date : 2024-03-28 Thassio Mesquita, Rodrigo Miguel-dos-Santos, Eugenio Cingolani
The human heart beats over 2 billion times during an average lifetime, driven by rhythmic depolarizations initiated by cardiac pacemaker cells within the sinoatrial node (SAN; Figure 1A). These electrical impulses are distributed throughout the heart via the cardiac conduction system (CCS), which synchronizes the excitation-contraction coupling of atrial and ventricular myocytes.1 Failure to generate
-
Gut Microbiota and Blood Metabolites Related to Fiber Intake and Type 2 Diabetes Circ. Res. (IF 20.1) Pub Date : 2024-03-28 Zheng Wang, Brandilyn A. Peters, Bing Yu, Megan L. Grove, Tao Wang, Xiaonan Xue, Bharat Thyagarajan, Martha L. Daviglus, Eric Boerwinkle, Gang Hu, Yasmin Mossavar-Rahmani, Carmen R. Isasi, Rob Knight, Robert D. Burk, Robert C. Kaplan, Qibin Qi
BACKGROUND:Consistent evidence suggests diabetes-protective effects of dietary fiber intake. However, the underlying mechanisms, particularly the role of gut microbiota and host circulating metabolites, are not fully understood. We aimed to investigate gut microbiota and circulating metabolites associated with dietary fiber intake and their relationships with type 2 diabetes (T2D).METHODS:This study
-
Extracellular Matrix Interactome in Modulating Vascular Homeostasis and Remodeling Circ. Res. (IF 20.1) Pub Date : 2024-03-28 Yi Fu, Yuan Zhou, Kai Wang, Zhuofan Li, Wei Kong
The ECM (extracellular matrix) is a major component of the vascular microenvironment that modulates vascular homeostasis. ECM proteins include collagens, elastin, noncollagen glycoproteins, and proteoglycans/glycosaminoglycans. ECM proteins form complex matrix structures, such as the basal lamina and collagen and elastin fibers, through direct interactions or lysyl oxidase-mediated cross-linking. Moreover
-
Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility Circ. Res. (IF 20.1) Pub Date : 2024-03-27 Roman Tikhomirov, Robert H. Oakley, Cali Anderson, Yirong Xiang, Sami Al Othman, Matthew Smith, Sana Yaar, Eleonora Torre, Jianying Li, Leslie R. Wilson, David R. Goulding, Ian Donaldson, Erika Harno, Luca Soattin, Holly A. Shiels, Gwilym M. Morris, Henggui Zhang, Mark R. Boyett, John A. Cidlowski, Pietro Mesirca, Matteo E. Mangoni, Alicia D’Souza
RATIONALE:Ventricular arrhythmias (VAs) demonstrate a prominent day-night rhythm, commonly presenting in the early morning. Transcriptional rhythms in cardiac ion channels accompany this phenomenon, but their role in the morning vulnerability to VAs and the underlying mechanisms are not understood.OBJECTIVE:The objectives are to investigate the recruitment of transcription factors to time-of-day differentially
-
AKAP12 Upregulation Associates With PDE8A to Accelerate Cardiac Dysfunction Circ. Res. (IF 20.1) Pub Date : 2024-03-20 Hanan Qasim, Mehrdad Rajaei, Ying Xu, Arfaxad Reyes-Alcaraz, Hala Y. Abdelnasser, M. David Stewart, Satadru K. Lahiri, Xander H.T. Wehrens, Bradley K. McConnell
BACKGROUND:In heart failure, signaling downstream the β2-adrenergic receptor is critical. Sympathetic stimulation of β2-adrenergic receptor alters cAMP (cyclic adenosine 3′,5′-monophosphate) and triggers PKA (protein kinase A)-dependent phosphorylation of proteins that regulate cardiac function. cAMP levels are regulated in part by PDEs (phosphodiesterases). Several AKAPs (A kinase anchoring proteins)
-
Circadian Rhythms in Cardiovascular Metabolism Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Hind Lal, Suresh Kumar Verma, Yajing Wang, Min Xie, Martin E. Young
Energetic demand and nutrient supply fluctuate as a function of time-of-day, in alignment with sleep-wake and fasting-feeding cycles. These daily rhythms are mirrored by 24-hour oscillations in numerous cardiovascular functional parameters, including blood pressure, heart rate, and myocardial contractility. It is, therefore, not surprising that metabolic processes also fluctuate over the course of
-
Circadian Regulation of Cardiac Arrhythmias and Electrophysiology Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Brian P. Delisle, Abhilash Prabhat, Don E. Burgess, Makoto Ono, Karyn A. Esser, Elizabeth A. Schroder
Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns
-
Circadian Influences on Myocardial Ischemia-Reperfusion Injury and Heart Failure Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Tobias Eckle, Júlia Bertazzo, Tarak Nath Khatua, Seyed Reza Fatemi Tabatabaei, Naghmeh Moori Bakhtiari, Lori A. Walker, Tami A. Martino
The impact of circadian rhythms on cardiovascular function and disease development is well established, with numerous studies in genetically modified animals emphasizing the circadian molecular clock’s significance in the pathogenesis and pathophysiology of myocardial ischemia and heart failure progression. However, translational preclinical studies targeting the heart's circadian biology are just
-
Circadian Mechanisms in Brain Fluid Biology Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Velia S. Vizcarra, Ryann M. Fame, Lauren M. Hablitz
The brain is a complex organ, fundamentally changing across the day to perform basic functions like sleep, thought, and regulating whole-body physiology. This requires a complex symphony of nutrients, hormones, ions, neurotransmitters and more to be properly distributed across the brain to maintain homeostasis throughout 24 hours. These solutes are distributed both by the blood and by cerebrospinal
-
Circadian Rhythms of the Blood-Brain Barrier and Drug Delivery Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Mari Kim, Richard F. Keep, Shirley L. Zhang
The blood-brain barrier (BBB) is a critical interface separating the central nervous system from the peripheral circulation, ensuring brain homeostasis and function. Recent research has unveiled a profound connection between the BBB and circadian rhythms, the endogenous oscillations synchronizing biological processes with the 24-hour light-dark cycle. This review explores the significance of circadian
-
Stroke in the Time of Circadian Medicine Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Philipp Mergenthaler, Joyce S. Balami, Ain A. Neuhaus, Amin Mottahedin, Gregory W. Albers, Peter M. Rothwell, Jeffrey L. Saver, Martin E. Young, Alastair M. Buchan
Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also for important determinants of clinical outcome. In this review, we provide a comprehensive overview of the interplay between chronobiology and cerebrovascular disease. We discuss circadian regulation of pathophysiological mechanisms underlying
-
LOX-1 and MMP-9 Inhibition Attenuates the Detrimental Effects of Delayed rt-PA Therapy and Improves Outcomes After Acute Ischemic Stroke Circ. Res. (IF 20.1) Pub Date : 2024-03-19 Kajsa Arkelius, Trevor S. Wendt, Henrik Andersson, Anaële Arnou, Michael Gottschalk, Rayna J. Gonzales, Saema Ansar
BACKGROUND:Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix
-
Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome Circ. Res. (IF 20.1) Pub Date : 2024-03-18 Francisco M. Cruz, Álvaro Macías, Ana I. Moreno-Manuel, Lilian K. Gutiérrez, María Linarejos Vera-Pedrosa, Isabel Martínez-Carrascoso, Patricia Sánchez Pérez, Juan Manuel Ruiz Robles, Francisco J. Bermúdez-Jiménez, Aitor Díaz-Agustín, Fernando Martínez de Benito, Salvador Arias-Santiago, Aitana Braza-Boils, Mercedes Martín-Martínez, Marta Gutierrez-Rodríguez, Juan A. Bernal, Esther Zorio, Juan Jiménez-Jaimez
BACKGROUND:Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154
-
Circadian Mechanisms in Cardiovascular and Cerebrovascular Disease Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Eng H. Lo, Frank M. Faraci
All living organisms on Earth demonstrate rhythms in biological function, which are approximately tied to the 24-hour cycle of a single day and night. The term diurnal is commonly used to describe events that occur during the day. For example, a diurnal species is the one that is mainly active during the daylight. In contrast, the term circadian refers to a rhythm that has a period of ≈24 hours but
-
Circadian Clock and Hypoxia Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Francesca Sartor, Borja Ferrero-Bordera, Jeffrey Haspel, Markus Sperandio, Paul M. Holloway, Martha Merrow
The timing of life on Earth is remarkable: between individuals of the same species, a highly similar temporal pattern is observed, with shared periods of activity and inactivity each day. At the individual level, this means that over the course of a single day, a person alternates between two states. They are either upright, active, and communicative or they lie down in a state of (un)consciousness
-
Circadian and Diurnal Regulation of Cerebral Blood Flow Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Alastair J.S. Webb, Elizabeth B. Klerman, Emiri T. Mandeville
Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular
-
Circadian Biology and the Neurovascular Unit Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Wenlu Li, Steffen Tiedt, Jennifer H. Lawrence, Mary E. Harrington, Erik S. Musiek, Eng H. Lo
Mammalian physiology and cellular function are subject to significant oscillations over the course of every 24-hour day. It is likely that these daily rhythms will affect function as well as mechanisms of disease in the central nervous system. In this review, we attempt to survey and synthesize emerging studies that investigate how circadian biology may influence the neurovascular unit. We examine
-
Circadian Effects on Vascular Immunopathologies Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Qun Zeng, Valeria Maria Oliva, María Ángeles Moro, Christoph Scheiermann
Circadian rhythms exert a profound impact on most aspects of mammalian physiology, including the immune and cardiovascular systems. Leukocytes engage in time-of-day–dependent interactions with the vasculature, facilitating the emigration to and the immune surveillance of tissues. This review provides an overview of circadian control of immune-vascular interactions in both the steady state and cardiovascular
-
Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure Circ. Res. (IF 20.1) Pub Date : 2024-03-14 Frank M. Faraci, Frank A.J.L. Scheer
Hypertension is extremely common, affecting approximately 1 in every 2 adults globally. Chronic hypertension is the leading modifiable risk factor for cardiovascular disease and premature mortality worldwide. Despite considerable efforts to define mechanisms that underlie hypertension, a potentially major component of the disease, the role of circadian biology has been relatively overlooked in both
-
Rewiring Endothelial Sphingolipid Metabolism to Favor S1P Over Ceramide Protects From Coronary Atherosclerosis Circ. Res. (IF 20.1) Pub Date : 2024-03-08 Onorina L. Manzo, Jasmine Nour, Linda Sasset, Alice Marino, Luisa Rubinelli, Sailesh Palikhe, Martina Smimmo, Yang Hu, Maria Rosaria Bucci, Alain Borczuk, Olivier Elemento, Julie K. Freed, Giuseppe Danilo Norata, Annarita Di Lorenzo
BACKGROUND:Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role in atherosclerosis. Yet, how sphingolipid metabolism and signaling change
-
CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis Circ. Res. (IF 20.1) Pub Date : 2024-03-08 Qiankun Bao, Bangying Zhang, Lu Zhou, Qian Yang, Xiaofeng Mu, Xing Liu, Shiying Zhang, Meng Yuan, Yue Zhang, Jingjin Che, Wen Wei, Tong Liu, Guangping Li, Jinlong He
BACKGROUND:CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms.METHODS:Plasma
-
Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function Circ. Res. (IF 20.1) Pub Date : 2024-03-08 Chen Li, Sara K. Ture, Benjamin Nieves-Lopez, Sara K. Blick-Nitko, Preeti Maurya, Alison C. Livada, Tyler J. Stahl, Minsoo Kim, Anthony P. Pietropaoli, Craig N. Morrell
BACKGROUND:While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions,
-
Characterization of Vascular Niche in Systemic Sclerosis by Spatial Proteomics Circ. Res. (IF 20.1) Pub Date : 2024-03-05 Aleix Rius Rigau, Yi-Nan Li, Alexandru-Emil Matei, Andrea-Hermina Györfi, Peter-Martin Bruch, Sarah Koziel, Veda Devakumar, Armando Gabrielli, Alexander Kreuter, Jiucun Wang, Sascha Dietrich, Georg Schett, Jörg H.W. Distler, Minrui Liang
BACKGROUND:Systemic sclerosis (SSc) is a connective tissue disease that can serve as a model to study vascular changes in response to inflammation, autoimmunity, and fibrotic remodeling. Although microvascular changes are the earliest histopathologic manifestation of SSc, the vascular pathophysiology remains poorly understood.METHODS:We applied spatial proteomic approaches to deconvolute the heterogeneity
-
Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes Circ. Res. (IF 20.1) Pub Date : 2024-02-29 Dan Zhao, Zeng-Kang Huang, Yu Liang, Zhi-Jun Li, Xue-Wei Zhang, Kun-Hang Li, Hao Wu, Xu-Dong Zhang, Chen-Sheng Li, Dong An, Xue Sun, Ming-Xin An, Jun-Xiu Shi, Yi-Jun Bao, Li Tian, Di-Fei Wang, An-Hua Wu, Yu-Hua Chen, Wei-Dong Zhao
BACKGROUND:Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined.METHODS:High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral
-
Cardiovascular Consequences of Uremic Metabolites: an Overview of the Involved Signaling Pathways Circ. Res. (IF 20.1) Pub Date : 2024-02-29 Adelina Curaj, Raymond Vanholder, Joseph Loscalzo, Kaiseng Quach, Zhuojun Wu, Vera Jankowski, Joachim Jankowski
The crosstalk of the heart with distant organs such as the lung, liver, gut, and kidney has been intensively approached lately. The kidney is involved in (1) the production of systemic relevant products, such as renin, as part of the most essential vasoregulatory system of the human body, and (2) in the clearance of metabolites with systemic and organ effects. Metabolic residue accumulation during
-
Early Career Research Support From the American Heart Association: to the Second Century and Beyond Circ. Res. (IF 20.1) Pub Date : 2024-02-29 Jessica Pfleger, Ronald J. Vagnozzi
On June 10, 2024, the American Heart Association (AHA) enters its 100th year as an organization dedicated to the fight against heart disease and stroke, thus fostering a world of longer, healthier lives. This critical work includes essential lifesaving measures such as annual CPR training for ≈22 million people and enrolling more than 2600 hospitals in Get With The Guidelines, a program that provides
-
In This Issue Circ. Res. (IF 20.1) Pub Date : 2024-02-29
Ponatinib is used for the treatment of particular cases of chronic myeloid leukemia (CML) that don’t respond to other medications. Unfortunately, the drug can have life-threatening cardiovascular side effects including cardiomyopathy and heart failure. Ponatinib is known to induce mitochondrial dysfunction, which is linked to the cellular stress response. But whether the drug itself activates the stress
-
PIEZO Ion Channels in Cardiovascular Functions and Diseases Circ. Res. (IF 20.1) Pub Date : 2024-02-29 Bertrand Coste, Patrick Delmas
The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after
-
Acute Adenoviral Infection Elicits an Arrhythmogenic Substrate Prior to Myocarditis Circ. Res. (IF 20.1) Pub Date : 2024-02-28 Rachel L. Padget, Michael J. Zeitz, Grace A. Blair, Xiaobo Wu, Michael D. North, Mira T. Tanenbaum, Kari E. Stanley, Chelsea M. Phillips, D. Ryan King, Samy Lamouille, Robert G. Gourdie, Gregory S. Hoeker, Sharon A. Swanger, Steven Poelzing, James W. Smyth
BACKGROUND:Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and a resulting lack of mechanistic understanding. Myocarditis is a major cause of sudden cardiac death in young adults, where current knowledge in the field is dominated by later disease phases and pathological immune responses. However, little
-
Stromal Cell-SLIT3/Cardiomyocyte-ROBO1 Axis Regulates Pressure Overload-Induced Cardiac Hypertrophy Circ. Res. (IF 20.1) Pub Date : 2024-02-27 Xiaoxiao Liu, Baolei Li, Shuyun Wang, Erge Zhang, Megan Schultz, Marlin Touma, Andre Monteiro Da Rocha, Sylvia M. Evans, Anne Eichmann, Todd Herron, Ruizhen Chen, Dingding Xiong, Alexander Jaworski, Stephen Weiss, Ming-Sing Si
BACKGROUND:Recently shown to regulate cardiac development, the secreted axon guidance molecule SLIT3 maintains its expression in the postnatal heart. Despite its known expression in the cardiovascular system after birth, SLIT3’s relevance to cardiovascular function in the postnatal state remains unknown. As such, the objectives of this study were to determine the postnatal myocardial sources of SLIT3
-
Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis Circ. Res. (IF 20.1) Pub Date : 2024-02-20 Chang Ma, Yihui Li, Mi Tian, Qiming Deng, Xiaoteng Qin, Hanlin Lu, Jiangang Gao, Min Chen, Lee S. Weinstein, Mei Zhang, Peili Bu, Jianmin Yang, Yun Zhang, Cheng Zhang, Wencheng Zhang
BACKGROUND:Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear.METHODS:High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression
-
Sorbs2 Deficiency and Vascular BK Channelopathy in Diabetes Circ. Res. (IF 20.1) Pub Date : 2024-02-16 Xiaojing Sun, Hon-Chi Lee, Tong Lu
BACKGROUND:Vascular large conductance Ca2+-activated K+ (BK) channel, composed of the α-subunit (BK-α) and the β1-subunit (BK-β1), is a key determinant of coronary vasorelaxation and its function is impaired in diabetic vessels. However, our knowledge of diabetic BK channel dysregulation is incomplete. The Sorbs2 (Sorbin homology [SoHo] and Src homology 3 [SH3] domains-containing protein 2), is ubiquitously
-
Retraction of: Age-Induced Accumulation of Succinate Promotes Cardiac Fibrogenesis Circ. Res. (IF 20.1) Pub Date : 2024-02-09
The following Circulation Research article is retracted: Wang et al. Age-Induced Accumulation of Succinate Promotes Cardiac Fibrogenesis. Circ Res. Originally published December 19, 2023. https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.123.323651 After publication, a number of data errors and duplicated figure panels were discovered. The figure panels with concerns include the following: Figures
-
Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity Circ. Res. (IF 20.1) Pub Date : 2024-02-07 Gege Yan, Zhenbo Han, Youjeong Kwon, Jordan Jousma, Sarath Babu Nukala, Benjamin L. Prosser, Xiaoping Du, Sandra Pinho, Sang-Bing Ong, Won Hee Lee, Sang-Ging Ong
BACKGROUND:Mitochondrial dysfunction is a primary driver of cardiac contractile failure; yet, the cross talk between mitochondrial energetics and signaling regulation remains obscure. Ponatinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia, is among the most cardiotoxic tyrosine kinase inhibitors and causes mitochondrial dysfunction. Whether ponatinib-induced mitochondrial dysfunction
-
Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells Circ. Res. (IF 20.1) Pub Date : 2024-02-07 Jing Wang, Shuqin Liu, Xinxiu Meng, Xuan Zhao, Tianhui Wang, Zhiyong Lei, H. Immo Lehmann, Guoping Li, Pilar Alcaide, Yihua Bei, Junjie Xiao
BACKGROUND:Doxorubicin is an effective chemotherapeutic agent, but its use is limited by acute and chronic cardiotoxicity. Exercise training has been shown to protect against doxorubicin-induced cardiotoxicity, but the involvement of immune cells remains unclear. This study aimed to investigate the role of exercise-derived B cells in protecting against doxorubicin-induced cardiotoxicity and to further
-
Reactive Oxygen Species Modulator 1 (ROMO1) Plays an Obligate Role in Cardiomyocyte Hypertrophy. Circ. Res. (IF 20.1) Pub Date : 2023-11-29 Matthew D Martens,Claudia D Holody,Lisa Wells,Heidi L Silver,Daniela Y Morales-Llamas,William W Du,Courtney Reeks,Mostafa Khairy,Huachen Chen,Mourad Ferdaoussi,Stephane L Bourque,Burton B Yang,John R Ussher,Helene Lemieux,Gavin Y Oudit,Robert A Screaton,Jason R B Dyck
-
-
-
Cooperative Response to Endocardial Notch Reveals Interaction With Hippo Pathway. Circ. Res. (IF 20.1) Pub Date : 2023-11-14 Luis Luna-Zurita,Brenda Giselle Flores-Garza,Dimitrios Grivas,Marcos Siguero-Álvarez,José Luis de la Pompa
BACKGROUND The endocardium is a crucial signaling center for cardiac valve development and maturation. Genetic analysis has identified several human endocardial genes whose inactivation leads to bicuspid aortic valve formation and calcific aortic valve disease, but knowledge is very limited about the role played in valve development and disease by noncoding endocardial regulatory regions and upstream
-
Nitric Oxide Modulates Ca2+ Leak and Arrhythmias via S-Nitrosylation of CaMKII. Circ. Res. (IF 20.1) Pub Date : 2023-11-14 Amelia S Power,Esther U Asamudo,Luke P I Worthington,Chidera C Alim,Raquel E Parackal,Rachel S Wallace,Obialunanma V Ebenebe,Joan Heller Brown,Mark J Kohr,Donald M Bers,Jeffrey R Erickson
BACKGROUND Nitric oxide (NO) has been identified as a signaling molecule generated during β-adrenergic receptor stimulation in the heart. Furthermore, a role for NO in triggering spontaneous Ca2+ release via S-nitrosylation of CaMKIIδ (Ca2+/calmodulin kinase II delta) is emerging. NO donors are routinely used clinically for their cardioprotective effects on the heart, but it is unknown how NO donors
-
Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation. Circ. Res. (IF 20.1) Pub Date : 2023-11-13 Hannah Knight,Giancarlo Abis,Manpreet Kaur,Hannah L H Green,Susanne Krasemann,Kristin Hartmann,Steven Lynham,James Clark,Lan Zhao,Clemens Ruppert,Astrid Weiss,Ralph T Schermuly,Philip Eaton,Olena Rudyk
BACKGROUND Pulmonary hypertension (PH) is a chronic vascular disease characterized, among other abnormalities, by hyperproliferative smooth muscle cells and a perturbed cellular redox and metabolic balance. Oxidants induce cell cycle arrest to halt proliferation; however, little is known about the redox-regulated effector proteins that mediate these processes. Here, we report a novel kinase-inhibitory
-
DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters. Circ. Res. (IF 20.1) Pub Date : 2023-11-13 Nienke M Stege,Tim R Eijgenraam,Vivian Oliveira Nunes Teixeira,Anna M Feringa,Elisabeth M Schouten,Diederik W D Kuster,Jolanda van der Velden,Anouk H G Wolters,Ben N G Giepmans,Catherine A Makarewich,Rhonda Bassel-Duby,Eric N Olson,Rudolf A de Boer,Herman H W Silljé
BACKGROUND The p.Arg14del variant of the PLN (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease. Dwarf open reading frame (DWORF) has been shown to counteract PLN regulatory calcium handling function in the sarco/endoplasmic reticulum (S/ER). Here, we investigated
-
NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation. Circ. Res. (IF 20.1) Pub Date : 2023-11-13 Jing Shi,Chuanxi Yang,Kun Zhao,Jing Zhang,Peng Li,Chuiyu Kong,Xiaoguang Wu,Haoliang Sun,Rui Zheng,Wei Sun,Lianmin Chen,Xiangqing Kong
BACKGROUND Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during cardiac remodeling. METHODS NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling
-
Disturbed Sleep Supports Neutrophil Activation and Promotes Atherosclerosis and Plaque Necrosis. Circ. Res. (IF 20.1) Pub Date : 2023-11-10 Alina K Moriarty,Tayab C Waseem,W Coles Keeter,Shelby D Ma,Robin Bai,Aleksandr V Ivanov,Cassandra L Kirk,Marion Mussbacher,Larry D Sanford,Elena V Galkina
-
Receptor-Specific Inside-Out cAMP Signaling Regulates Cardiomyocyte Fate. Circ. Res. (IF 20.1) Pub Date : 2023-11-09 Frank Lezoualc'h,Viacheslav O Nikolaev
-
New Way to Study Pulmonary Hypertension in HFpEF. Circ. Res. (IF 20.1) Pub Date : 2023-11-09 Zhiyu Dai,Edward Benjamin Thorp