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Endothelial Cell Flow–Mediated Quiescence Is Temporally Regulated and Utilizes the Cell Cycle Inhibitor p27 Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-11 Natalie T. Tanke, Ziqing Liu, Michaelanthony T. Gore, Pauline Bougaran, Mary B. Linares, Allison Marvin, Arya Sharma, Morgan Oatley, Tianji Yu, Kaitlyn Quigley, Sarah Vest, Jeanette Gowen Cook, Victoria L. Bautch
BACKGROUND:Endothelial cells regulate their cell cycle as blood vessels remodel and transition to quiescence downstream of blood flow–induced mechanotransduction. Laminar blood flow leads to quiescence, but how flow-mediated quiescence is established and maintained is poorly understood.METHODS:Primary human endothelial cells were exposed to laminar flow regimens and gene expression manipulations, and
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Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-11 Ilakya Selvarajan, Miika Kiema, Ru-Ting Huang, Jin Li, Jiayu Zhu, Petri Pölönen, Tiit Örd, Kadri Õunap, Mehvash Godiwala, Anna Kathryn Golebiewski, Aarthi Ravindran, Kiira Mäklin, Anu Toropainen, Lindsey K. Stolze, Maximiliano Arce, Peetra U. Magnusson, Stephen White, Casey E. Romanoski, Merja Heinäniemi, Johanna P. Laakkonen, Yun Fang, Minna Kaikkonen-Määttä
BACKGROUND:CALCRL (calcitonin receptor-like) protein is an important mediator of the endothelial fluid shear stress response, which is associated with the genetic risk of coronary artery disease. In this study, we functionally characterized the noncoding regulatory elements carrying coronary artery disease that risks single-nucleotide polymorphisms and studied their role in the regulation of CALCRL
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Arterial Smooth Muscle Cell AKAP150 Mediates Exercise-Induced Repression of CaV1.2 Channel Function in Cerebral Arteries of Hypertensive Rats Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-11 Yanyan Zhang, Zhaoxia Xu, Meiling Shan, Jiaqi Cao, Yang Zhou, Yu Chen, Lijun Shi
BACKGROUND:Hypertension is a major, prevalent risk factor for the development and progression of cerebrovascular disease. Regular exercise has been recommended as an excellent choice for the large population of individuals with mild-to-moderate elevations in blood pressure, but the mechanisms that underlie its vascular-protective and antihypertensive effects remain unknown. Here, we describe a mechanism
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HMGB2 Release Promotes Pulmonary Hypertension and Predicts Severity and Mortality of Patients With Pulmonary Arterial Hypertension Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-04 Deping Kong, Jing Liu, Junmi Lu, Cheng Zeng, Hao Chen, Zhenzhen Duan, Ke Yu, Xialei Zheng, Pu Zou, Liufang Zhou, Yicheng Lv, Qingye Zeng, Lin Lu, Jiang Li, Yuhu He
BACKGROUND:Pulmonary hypertension (PH) is a progressive and life-threatening disease characterized by pulmonary vascular remodeling, which involves aberrant proliferation and apoptosis resistance of the pulmonary arterial smooth muscle cells (PASMCs), resembling the hallmark characteristics of cancer. In cancer, the HMGB2 (high-mobility group box 2) protein promotes the pro-proliferative/antiapoptotic
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Glycoursodeoxycholic Acid Alleviates Arterial Thrombosis via Suppressing Diacylglycerol Kinases Activity in Platelet Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-04 Wenchao Yang, Ruijia Feng, Guiyan Peng, Zhecun Wang, Meifeng Cen, Yexiang Jing, Weiqi Feng, Ting Long, Yunchong Liu, Zilun Li, Kan Huang, Guangqi Chang
BACKGROUND:Glycoursodeoxycholic acid (GUDCA) has been acknowledged for its ability to regulate lipid homeostasis and provide benefits for various metabolic disorders. However, the impact of GUDCA on arterial thrombotic events remains unexplored. The objective of this study is to examine the effects of GUDCA on thrombogenesis and elucidate its underlying mechanisms.METHODS:Plasma samples from patients
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Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-04 Shintaro Takeda, Takuo Emoto, Tomoya Yamashita, Hiroyuki Yamamoto, Tomofumi Takaya, Takahiro Sawada, Takeshi Yoshida, Masatoshi Inoue, Yuya Suzuki, Tomoyo Hamana, Taishi Inoue, Masayuki Taniguchi, Naoto Sasaki, Hiromasa Otake, Takenao Ohkawa, Tomoyuki Furuyashiki, Hiroya Kawai, Ken-ichi Hirata
BACKGROUND:Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic
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Hemodynamics and Wall Mechanics of Vascular Graft Failure Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-04 Jason M. Szafron, Elbert E. Heng, Jack Boyd, Jay D. Humphrey, Alison L. Marsden
Blood vessels are subjected to complex biomechanical loads, primarily from pressure-driven blood flow. Abnormal loading associated with vascular grafts, arising from altered hemodynamics or wall mechanics, can cause acute and progressive vascular failure and end-organ dysfunction. Perturbations to mechanobiological stimuli experienced by vascular cells contribute to remodeling of the vascular wall
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Angiotensinogen as a Therapeutic Target for Cardiovascular and Metabolic Diseases Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-04-04 Alan Daugherty, Hisashi Sawada, Mary B. Sheppard, Hong S. Lu
AGT (angiotensinogen) is the unique precursor for the generation of all the peptides of the renin-angiotensin system, but it has received relatively scant attention compared to many other renin-angiotensin system components. Focus on AGT has increased recently, particularly with the evolution of drugs to target the synthesis of the protein. AGT is a noninhibitory serpin that has several conserved domains
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Lipoprotein Particles in Cerebrospinal Fluid Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-28 Maki Tsujita, John T. Melchior, Shinji Yokoyama
The brain is the most lipid-rich organ in the body, and the intricate interplay between lipid metabolism and pathologies associated with neurodegenerative disorders is being increasingly recognized. The brain is bathed in cerebrospinal fluid (CSF), which, like plasma, contains lipid-protein complexes called lipoproteins that are responsible for extracellular lipid transport. Multiple CSF lipoprotein
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Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-28 Md Torikul Islam, Jinjin Cai, Shanena Allen, Denisse G. Moreno, Samuel I. Bloom, R. Colton Bramwell, Jonathan Mitton, Andrew G. Horn, Weiquan Zhu, Anthony J. Donato, William L. Holland, Lisa A. Lesniewski
BACKGROUND:Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays
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Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-28 Frederick J. Raal, Robert A. Hegele, Andrea Ruzza, J. Antonio G. López, Ajay K. Bhatia, Johnny Wu, Huei Wang, Daniel Gaudet, Albert Wiegman, Jian Wang, Raul D. Santos
BACKGROUND:Pediatric patients with homozygous familial hypercholesterolemia (HoFH) have an increased risk of atherosclerotic cardiovascular disease and difficulty meeting low-density lipoprotein cholesterol (LDL-C) goals. In this post hoc analysis, we evaluated pooled safety and efficacy data from 3 studies in pediatric patients with HoFH treated with the PCSK9 (proprotein convertase subtilisin/kexin
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Evaluation of Plasma Biomarkers for Causal Association With Peripheral Artery Disease Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-28 Pranav Sharma, Derek Klarin, Benjamin F. Voight, Philip S. Tsao, Michael G. Levin, Scott M. Damrauer
BACKGROUND:Hundreds of biomarkers for peripheral artery disease (PAD) have been reported in the literature; however, the observational nature of these studies limits causal inference due to the potential of reverse causality and residual confounding. We sought to evaluate the potential causal impact of putative PAD biomarkers identified in human observational studies through genetic causal inference
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Multi-Omics and Single-Cell Omics: New Tools in Drug Target Discovery Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-27 Joseph Loscalzo
Biological systems are inherently noisy, with noise caused by the measurement process (ie, technical noise) and by inherent biological variability (ie, biological noise). Biological noise accounts for phenotypic differences within a population of individuals, as well as differences between two different cells of the same lineage within an organ of a single individual. Biomedical investigators typically
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Challenges and Opportunities in Valvular Heart Disease: From Molecular Mechanisms to the Community Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-27 Elena Aikawa, Mark C. Blaser, Sasha A. Singh, Robert A. Levine, Magdi H. Yacoub
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Clonal Hematopoiesis: The Emergent CVD Risk Factor Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-27 Jesse D. Cochran, Kenneth Walsh
In 1948, the Framingham Heart Study (FHS) was commissioned to elucidate commonalities that may contribute to cardiovascular disease (CVD).1 Through this work, many of the core risk factors for CVD were established by the late 1970s. Despite these major advances, it has long been recognized that the conventional modifiable risk factors incompletely account for the incidence of CVD.2 In view of this
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Monocyte-Mediated Thrombosis Linked to Circulating Tissue Factor and Immune Paralysis in COVID-19 Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-21 Sascha N. Goonewardena, Qinzhong Chen, Ashley M. Tate, Olga G. Grushko, Dilna Damodaran, Pennelope Blakely, Salim S. Hayek, David J. Pinsky, Robert S. Rosenson
BACKGROUND:SARS-CoV-2 infections cause COVID-19 and are associated with inflammation, coagulopathy, and high incidence of thrombosis. Myeloid cells help coordinate the initial immune response in COVID-19. Although we appreciate that myeloid cells lie at the nexus of inflammation and thrombosis, the mechanisms that unite the two in COVID-19 remain largely unknown.METHODS:In this study, we used systems
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Remnant Cholesterol, Not LDL Cholesterol, Explains Peripheral Artery Disease Risk Conferred by apoB: A Cohort Study Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-21 Benjamin N. Wadström, Kasper M. Pedersen, Anders B. Wulff, Børge G. Nordestgaard
BACKGROUND:Elevated apoB-containing lipoproteins (=remnants+LDLs [low-density lipoproteins]) are a major risk factor for atherosclerotic cardiovascular disease, including peripheral artery disease (PAD) and myocardial infarction. We tested the hypothesis that remnants and LDL both explain part of the increased risk of PAD conferred by elevated apoB-containing lipoproteins. For comparison, we also studied
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Virus-Associated CD8+ T-Cells Are Not Activated Through Antigen-Mediated Interaction Inside Atherosclerotic Lesions Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-21 Maaike J.M. de Jong, Frank H. Schaftenaar, Marie A.C. Depuydt, Fernando Lozano Vigario, George M.C. Janssen, Judith A.H.M. Peeters, Lauren Goncalves, Anouk Wezel, Harm J. Smeets, Johan Kuiper, Ilze Bot, Peter van Veelen, Bram Slütter
INTRODUCTION:Viral infections have been associated with the progression of atherosclerosis and CD8+ T-cells directed against common viruses, such as influenza, Epstein-Barr virus, and cytomegalovirus, have been detected inside human atherosclerotic lesions. These virus-specific CD8+ T-cells have been hypothesized to contribute to the development of atherosclerosis; however, whether they affect disease
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Novel Angiogenesis Role of GLP-1(32–36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R–Dependent Glycolysis in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-21 Yikai Zhang, Shengyao Wang, Qiao Zhou, Yi Xie, Yepeng Hu, Weihuan Fang, Changxin Yang, Zhe Wang, Shu Ye, Xinyi Wang, Chao Zheng
BACKGROUND:Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32–36)—an end product of GLP-1—on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1
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Role of Colchicine in Cardiovascular Disease Management Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-21 Leo F. Buckley, Peter Libby
Colchicine—an anti-inflammatory alkaloid—has assumed an important role in the management of cardiovascular inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in extremely high doses for the treatment of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine effectively treats acute gout attacks, lowers
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Zebrafish ApoB-Containing Lipoprotein Metabolism: A Closer Look Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-14 Tabea Moll, Steven A. Farber
Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile. Zebrafish with mutations in genes linked to human metabolic diseases often mimic the human phenotype. Zebrafish larvae
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Identification of New Markers of Angiogenic Sprouting Using Transcriptomics: New Role for RND3 Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-14 Colette A. Abbey, Camille L. Duran, Zhishi Chen, Yanping Chen, Sukanya Roy, Ashley Coffell, Timothy M. Sveeggen, Sanjukta Chakraborty, Gregg B. Wells, Jiang Chang, Kayla J. Bayless
BACKGROUND:New blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported.METHODS:Using a model of human endothelial cell sprout initiation, we developed a protocol to physically separate
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Prior Exposure to Experimental Preeclampsia Increases Atherosclerotic Plaque Inflammation in Atherogenic Mice—Brief Report Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-03-07 Lauren A. Biwer, Joshua J. Man, Nicholas D. Camarda, Brigett V. Carvajal, S. Ananth Karumanchi, Iris Z. Jaffe
BACKGROUND:Women with a history of preeclampsia have evidence of premature atherosclerosis and increased risk of myocardial infarction and stroke compared with women who had a normotensive pregnancy. Whether this is due to common risk factors or a direct impact of prior preeclampsia exposure has never been tested in a mouse atherosclerosis model.METHODS:Pregnant LDLR-KO (low-density lipoprotein receptor
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TF-FVIIa PAR2-β-Arrestin Signaling Sustains Organ Dysfunction in Coxsackievirus B3 Infection of Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Meike Kespohl, Carl Christoph Goetzke, Nadine Althof, Clara Bredow, Nicolas Kelm, Sandra Pinkert, Thomas Bukur, Valesca Bukur, Kristin Grunz, Dilraj Kaur, Arnd Heuser, Michael Mülleder, Martina Sauter, Karin Klingel, Hartmut Weiler, Nikolaus Berndt, Matthias M. Gaida, Wolfram Ruf, Antje Beling
BACKGROUND:Accumulating evidence implicates the activation of G-protein–coupled PARs (protease-activated receptors) by coagulation proteases in the regulation of innate immune responses.METHODS:Using mouse models with genetic alterations of the PAR2 signaling platform, we have explored contributions of PAR2 signaling to infection with coxsackievirus B3, a single-stranded RNA virus provoking multiorgan
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High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Alexander C. Bashore, Hanying Yan, Chenyi Xue, Lucie Y. Zhu, Eunyoung Kim, Thomas Mawson, Johana Coronel, Allen Chung, Nadja Sachs, Sebastian Ho, Leila S. Ross, Michael Kissner, Emmanuelle Passegué, Robert C. Bauer, Lars Maegdefessel, Mingyao Li, Muredach P. Reilly
BACKGROUND:Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited.METHODS:To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and
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Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Thassio Mesquita, Yen-Nien Lin, Shuang Chen, Youngho Lee, Rodrigo Miguel-dos-Santos, Asli E. Atici, Michael C. Fishbein, Magali Noval Rivas, Moshe Arditi, Eugenio Cingolani
BACKGROUND:Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities
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Use of Genomics to Develop Novel Therapeutics and Personalize Hypertension Therapy Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Emma F. Magavern, Vikas Kapil, Manish Saxena, Ajay Gupta, Mark J. Caulfield
Hypertension is a prevalent public health problem, contributing to >10 million deaths annually. Though multiple therapeutics exist, many patients suffer from treatment-resistant hypertension or try several medications before achieving blood pressure control. Genomic advances offer mechanistic understanding of blood pressure variability, therapeutic targets, therapeutic response, and promise a stratified
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Differences in Cardiometabolic Proteins in Pregnancy Prioritize Relevant Targets of Preeclampsia Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Kathryn J. Lindley, Andrew Perry, Marni Jacobs, Lauren Petty, Kaushik Amancherla, Shilin Zhao, Claire Barker, Victor G. Davila-Roman, Sadiya S. Khan, Sarah S. Osmundson, Kahraman Tanriverdi, Jane E. Freedman, Jennifer Below, Ravi V. Shah, Louise C. Laurent
BACKGROUND:Preeclampsia is a hypertensive disorder of pregnancy characterized by widespread vascular inflammation. It occurs frequently in pregnancy, often without known risk factors, and has high rates of maternal and fetal morbidity and mortality. Identification of biomarkers that predict preeclampsia and its cardiovascular sequelae before clinical onset, or even before pregnancy, is a critical unmet
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Calcium Signaling in Airway Epithelial Cells: Current Understanding and Implications for Inflammatory Airway Disease Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Amit Jairaman, Murali Prakriya
Airway epithelial cells play an indispensable role in protecting the lung from inhaled pathogens and allergens by releasing an array of mediators that orchestrate inflammatory and immune responses when confronted with harmful environmental triggers. While this process is undoubtedly important for containing the effects of various harmful insults, dysregulation of the inflammatory response can cause
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ANGPTL3 Downregulation Increases Intracellular Lipids by Reducing Energy Utilization Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Grazia Pennisi, Samantha Maurotti, Ester Ciociola, Oveis Jamialahmadi, Giorgio Bertolazzi, Angela Mirarchi, Per-Olof Bergh, Francesca Scionti, Rosellina M. Mancina, Rocco Spagnuolo, Claudio Tripodo, Jan Boren, Salvatore Petta, Stefano Romeo
Background:ANGPTL3 (angiopoietin-like protein 3) is a circulating protein with a key role in maintaining lipoprotein homeostasis. A monoclonal antibody against ANGPTL3 is an approved and well-tolerated treatment to reduce lipoproteins in familial hypercholesterolemia homozygotes. However, the reduction of hepatic ANGPTL3 synthesis using an antisense oligonucleotide unexpectedly resulted in a dose-dependent
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Reduced Monocyte and Neutrophil Infiltration and Activation by P-Selectin/CD62P Inhibition Enhances Thrombus Resolution in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-22 Julia B. Kral-Pointner, Patrick Haider, Petra L. Szabo, Manuel Salzmann, Mira Brekalo, Karl H. Schneider, Waltraud C. Schrottmaier, Christoph Kaun, Sonja Bleichert, Attila Kiss, Romana Sickha, Christian Hengstenberg, Kurt Huber, Christine Brostjan, Helga Bergmeister, Alice Assinger, Bruno K. Podesser, Johann Wojta, Philipp Hohensinner
BACKGROUND:Venous thromboembolism is a major health problem. After thrombus formation, its resolution is essential to re-establish blood flow, which is crucially mediated by infiltrating neutrophils and monocytes in concert with activated platelets and endothelial cells. Thus, we aimed to modulate leukocyte function during thrombus resolution post-thrombus formation by blocking P-selectin/CD62P-mediated
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Tissue Factor and COVID-19 Associated Thrombosis Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-21 Nigel Mackman
Microbial infections activate the innate and adaptive immune systems.1 Pathogen-associated molecular patterns produced by microbes, such as double-stranded RNA, are detected by PRRs (pattern-recognition receptors), such as toll-like receptor 3, and this leads to the expression of interferons and cytokines.1,2
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Correction to: Long Noncoding RNA Gpr137b-ps Promotes Advanced Atherosclerosis via the Regulation of Autophagy in Macrophages Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-21
The authors of the following Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) article have requested a clarification: Qu et al. Long Noncoding RNA Gpr137b-ps Promotes Advanced Atherosclerosis via the Regulation of Autophagy in Macrophages. Arterioscler Thromb Vasc Biol. 2023;43:e468–e489. https://www.ahajournals.org/doi/10.1161/ATVBAHA.123.319037. After publication, questions were raised about
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Valvular Prostaglandins Are Elevated in Severe Human Aortic Valve Stenosis Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-15 Lucien G.J. Cayer, Arun Surendran, Tobias Karakach, Harold M. Aukema, Amir Ravandi
BACKGROUND:Aortic valve stenosis (AVS) is the most common valvular disease in the developed world. AVS involves the progressive fibrocalcific remodeling of the aortic valve (AV), which impairs function and can ultimately lead to heart failure. Due to gaps in our understanding of the underlying mechanisms of AVS, there are no pharmacological treatments or dietary interventions known to slow AVS progression
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PAR4 Antagonism in Patients With Coronary Artery Disease Receiving Antiplatelet Therapies Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-15 Jennifer Nash, Mohammed N. Meah, Beth Whittington, Samuel Debono, Jennifer Raftis, Mark R. Miller, Andrew Sorbie, Nicholas L. Mills, Josselin Nespoux, Lorraine Bruce, Rodger Duffin, Neeraj Dhaun, Mairi Brittan, Longfei Chao, Samira Merali, Minji Kim, Zhaoqing Wang, Yue Zhang, Shiqiang Jin, Beqing Wang, Marc Kozinn, David E. Newby
BACKGROUND:BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease
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Single-Cell Transcriptome Reveals Potential Mechanisms for Coronary Artery Lesions in Kawasaki Disease Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-15 Yeshi Chen, Minna Yang, Mingming Zhang, Hongmao Wang, Yang Zheng, Rui Sun, Xiaohui Li
BACKGROUND:Coronary artery lesions (CALs) are the most common and major complication of Kawasaki disease (KD) in developed countries. However, the underlying immunologic mechanisms of CAL development in KD remain unclear.METHODS:Here, we conducted single-cell transcriptome analyses of 212 210 peripheral blood mononuclear cells collected from a cross-sectional cohort of 16 children, including 4 patients
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Microvascular Network Remodeling in the Ischemic Mouse Brain Defined by Light Sheet Microscopy Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-15 Nina Hagemann, Yachao Qi, Ayan Mohamud Yusuf, AnRan Li, Anthony Squire, Tobias Tertel, Bernd Giebel, Peter Ludewig, Philippa Spangenberg, Jianxu Chen, Axel Mosig, Matthias Gunzer, Dirk M. Hermann
BACKGROUND:Until now, the analysis of microvascular networks in the reperfused ischemic brain has been limited due to tissue transparency challenges.METHODS:Using light sheet microscopy, we assessed microvascular network remodeling in the striatum from 3 hours to 56 days post-ischemia in 2 mouse models of transient middle cerebral artery occlusion lasting 20 or 40 minutes, resulting in mild ischemic
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Angiogenesis in Chronic Thromboembolic Pulmonary Hypertension: A Janus-Faced Player? Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-08 Lynn Willems, Kondababu Kurakula, Janne Verhaegen, Frederikus A. Klok, Marion Delcroix, Marie-José Goumans, Rozenn Quarck
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension characterized by the presence of organized thrombi that obstruct pulmonary arteries, ultimately leading to right heart failure and death. Among others, impaired angiogenesis and inflammatory thrombosis have been shown to contribute to the progression of CTEPH. In this review, we summarize the 2-faced nature
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Plasma S1P Orchestrates the Reverse Transendothelial Migration of Aortic Intimal Myeloid Cells in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-08 Chanele K. Polenz, Corey A. Scipione, Sharon J. Hyduk, Marwan G. Althagafi, Hisham M. Ibrahim, Myron I. Cybulsky
BACKGROUND:Myeloid cells (MCs) reside in the aortic intima at regions predisposed to atherosclerosis. Systemic inflammation triggers reverse transendothelial migration (RTM) of intimal MCs into the arterial blood, which orchestrates a protective immune response that clears intracellular pathogens from the arterial intima. Molecular pathways that regulate RTM remain poorly understood. S1P (sphingosine-1-phosphate)
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Secreted Protein Profiling of Human Aortic Smooth Muscle Cells Identifies Vascular Disease Associations Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-08 Rédouane Aherrahrou, Ferheen Baig, Konstantinos Theofilatos, Dillon Lue, Alicia Beele, Tiit Örd, Minna U. Kaikkonen, Zouhair Aherrahrou, Qi Cheng, Saikat Kumar B. Ghosh, Santosh Karnewar, Vaishnavi Karnewar, Aloke V. Finn, Gary K. Owens, Michael Joner, Manuel Mayr, Mete Civelek
BACKGROUND:Smooth muscle cells (SMCs), which make up the medial layer of arteries, are key cell types involved in cardiovascular disease, the leading cause of mortality and morbidity worldwide. In response to microenvironment alterations, SMCs dedifferentiate from a contractile to a synthetic phenotype characterized by an increased proliferation, migration, production of ECM (extracellular matrix)
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p53 Acetylation Exerts Critical Roles in Pressure Overload–Induced Coronary Microvascular Dysfunction and Heart Failure in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-08 Xiaochen He, Aubrey C. Cantrell, Quinesha A. Williams, Wei Gu, Yingjie Chen, Jian-Xiong Chen, Heng Zeng
BACKGROUND:Coronary microvascular dysfunction (CMD) has been shown to contribute to cardiac hypertrophy and heart failure (HF) with preserved ejection fraction. At this point, there are no proven treatments for CMD.METHODS:We have shown that histone acetylation may play a critical role in the regulation of CMD. By using a mouse model that replaces lysine with arginine at residues K98, K117, K161, and
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Predicting Lipid-Rich Plaque Progression in Coronary Arteries Using Multimodal Imaging and Wall Shear Stress Signatures Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-08 Giuseppe De Nisco, Eline M.J. Hartman, Elena Torta, Joost Daemen, Claudio Chiastra, Diego Gallo, Umberto Morbiducci, Jolanda J. Wentzel
BACKGROUND:Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid
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Coronary Microvascular Dysfunction Is Associated With a Proinflammatory Circulating Transcriptome in Patients With Nonobstructive Coronary Arteries Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-01 Nathaniel R. Smilowitz, Florencia Schlamp, Anaïs Hausvater, Amanda Joa, Claudia Serrano-Gomez, Ayman Farid, Judith S. Hochman, Tessa J. Barrett, Harmony R. Reynolds, Jeffrey S. Berger
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Neutrophils and Neutrophil Extracellular Traps Cause Vascular Occlusion and Delayed Cerebral Ischemia After Subarachnoid Hemorrhage in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-01 Hussein A. Zeineddine, Sung-Ha Hong, Pedram Peesh, Ari Dienel, Kiara Torres, Peeyush Thankamani Pandit, Kanako Matsumura, Shuning Huang, Wen Li, Anjali Chauhan, John P. Hagan, Sean P. Marrelli, Louise D. McCullough, Spiros L. Blackburn, Jaroslaw Aronowski, Devin W. McBride
BACKGROUND:After subarachnoid hemorrhage (SAH), neutrophils are deleterious and contribute to poor outcomes. Neutrophils can produce neutrophil extracellular traps (NETs) after ischemic stroke. Our hypothesis was that, after SAH, neutrophils contribute to delayed cerebral ischemia (DCI) and worse outcomes via cerebrovascular occlusion by NETs.METHODS:SAH was induced via endovascular perforation, and
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Spatial Metabolomics Identifies LPC(18:0) and LPA(18:1) in Advanced Atheroma With Translation to Plasma for Cardiovascular Risk Estimation Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-01 Jianhua Cao, Marta Martin-Lorenzo, Kim van Kuijk, Elias B. Wieland, Marion J. Gijbels, Britt S.R. Claes, Angeles Heredero, Gonzalo Aldamiz-Echevarria, Ron M.A. Heeren, Pieter Goossens, Judith C. Sluimer, Benjamin Balluff, Gloria Alvarez-Llamas
BACKGROUND:The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed
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Regulation of YAP Promotor Accessibility in Endothelial Mechanotransduction Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-02-01 Aarren J. Mannion, Honglei Zhao, Yuanyuan Zhang, Ylva von Wright, Otto Bergman, Joy Roy, Pipsa Saharinen, Lars Holmgren
BACKGROUND:Endothelial cells are constantly exposed to mechanical forces in the form of fluid shear stress, extracellular stiffness, and cyclic strain. The mechanoresponsive activity of YAP (Yes-associated protein) and its role in vascular development are well described; however, whether changes to transcription or epigenetic regulation of YAP are involved in these processes remains unanswered. Furthermore
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Nonpreferential but Detrimental Accumulation of Macrophages With Clonal Hematopoiesis-Driver Mutations in Cardiovascular Tissues—Brief Report Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-25 Tsai-Sang Dederichs, Assel Yerdenova, Hauke Horstmann, Tamara Antonela Vico, Simone Nübling, Rémi Peyronnet, Dietmar Pfeifer, Constantin von zur Muehlen, Timo Heidt, Dennis Wolf, Martin Czerny, Dirk Westermann, Ingo Hilgendorf
BACKGROUND:Clonal hematopoiesis of indeterminate potential (CHIP) is an acquired genetic risk factor for both leukemia and cardiovascular disease. It results in proinflammatory myeloid cells in the bone marrow and blood; however, how these cells behave in the cardiovascular tissue remains unclear. Our study aimed at investigating whether CHIP-mutated macrophages accumulate preferentially in cardiovascular
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Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133+TRPV4high Endothelial Subpopulation in Regulating Flow-Induced Vascular Tone in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-25 Aiqin Mao, Ka Zhang, Hao Kan, Mengru Gao, Zhiwei Wang, Tingting Zhou, Jing Shao, Dongxu He
BACKGROUND:Single-cell RNA-Seq analysis can determine the heterogeneity of cells between different tissues at a single-cell level. Coronary artery endothelial cells (ECs) are important to coronary blood flow. However, little is known about the heterogeneity of coronary artery ECs, and cellular identity responses to flow. Identifying endothelial subpopulations will contribute to the precise localization
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Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-25 Kim E. Dzobo, Arjen J. Cupido, Barend M. Mol, Lotte C.A. Stiekema, Miranda Versloot, Maaike Winkelmeijer, Jorge Peter, Anne-Marije Pennekamp, Stefan R. Havik, Frédéric M. Vaz, Michel van Weeghel, Koen H.M. Prange, Johannes H.M. Levels, Menno P.J. de Winther, Sotirios Tsimikas, Albert K. Groen, Erik S.G. Stroes, Dominique P.V. de Kleijn, Jeffrey Kroon
BACKGROUND:Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a).METHODS:Untargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The
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New Mechanistic Insight Into Biased Signaling of Proteinase-Activated Receptor 1 Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-25 Katsuya Hirano
PAR1 (proteinase-activated receptor 1) is a G protein-coupled receptor that was originally identified as a signaling receptor that mediates the cellular effects of thrombin. A variety of proteinases, including those involved in coagulation and fibrinolysis, which are relevant to vascular physiology and pathophysiology, are now known to serve as agonists of PAR1.1,2 Currently, 4 subtypes of PAR, PAR1≈PAR4
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Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-25 Victoria Osinski, Amritha Yellamilli, Maria M. Firulyova, Michael J. Zhang, Alyssa L. Peck, Jennifer L. Auger, Jessica L. Faragher, Aubyn Marath, Rochus K. Voeller, Timothy D. O’Connell, Konstantin Zaitsev, Bryce A. Binstadt
BACKGROUND:Rheumatic heart disease is the major cause of valvular heart disease in developing nations. Endothelial cells (ECs) are considered crucial contributors to rheumatic heart disease, but greater insight into their roles in disease progression is needed.METHODS:We used a Cdh5-driven EC lineage-tracing approach to identify and track ECs in the K/B.g7 model of autoimmune valvular carditis. Single-cell
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Prostanoids in Cardiac and Vascular Remodeling Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-25 Emanuela Ricciotti, Philip G. Haines, William Chai, Garret A. FitzGerald
Prostanoids are biologically active lipids generated from arachidonic acid by the action of the COX (cyclooxygenase) isozymes. NSAIDs, which reduce the biosynthesis of prostanoids by inhibiting COX activity, are effective anti-inflammatory, antipyretic, and analgesic drugs. However, their use is limited by cardiovascular adverse effects, including myocardial infarction, stroke, hypertension, and heart
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Food Intake Suppresses ApoB Secretion and Fractional Catabolic Rates in Humans Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-24 Chunyu Zheng, Allison B. Andraski, Christina Khoo, Jeremy D. Furtado, Frank M. Sacks
BACKGROUND: Humans spend much of the day in the postprandial state. However, most research and clinical guidelines on plasma lipids pertain to blood drawn after a 12-hour fast. We aimed to study the metabolic differences of apoB lipoproteins between the fasting and postprandial states. METHODS: We investigated plasma apoB metabolism using stable isotope tracers in 12 adult volunteers under fasting
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Genome-Wide Genetic Associations Prioritize Evaluation of Causal Mechanisms of Atherosclerotic Disease Risk Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-24 Thomas Quertermous, Daniel Yuhang Li, Chad S. Weldy, Markus Ramste, Disha Sharma, João P. Monteiro, Wenduo Gu, Matthew D. Worssam, Brian T. Palmisano, Chong Y. Park, Paul Cheng
OBJECTIVE: The goal of this review is to discuss the implementation of genome-wide association studies to identify causal mechanisms of vascular disease risk. APPROACH AND RESULTS: The history of genome-wide association studies is described, the use of imputation and the creation of consortia to conduct meta-analyses with sufficient power to arrive at consistent associated loci for vascular disease
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Dietary Vitamin K 1 Intake and Incident Aortic Valve Stenosis Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-24 Carl J. Schultz, Frederik Dalgaard, Jamie W. Bellinge, Kevin Murray, Marc Sim, Emma Connolly, Lauren C. Blekkenhorst, Catherine P. Bondonno, Joshua R. Lewis, Gunnar H. Gislason, Anne Tjønneland, Kim Overvad, Jonathan M. Hodgson, Nicola P. Bondonno
BACKGROUND: Leaflet calcification contributes to the development and progression of aortic valve stenosis. Vitamin K activates inhibitors of vascular calcification and may modulate inflammation and skeletal bone loss. Therefore, we aimed to determine whether higher dietary intakes of vitamin K 1 are associated with a lower incidence of aortic stenosis. METHODS: In the Danish Diet, Cancer and Health
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Exosomes From IgE-Stimulated Mast Cells Aggravate Asthma-Mediated Atherosclerosis Through circRNA CDR1as-Mediated Endothelial Cell Dysfunction in Mice Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-18 Hongqin Yang, Junye Chen, Siyang Liu, Yunfei Xue, Zhiwei Li, Tao Wang, Liqun Jiao, Qi An, Bao Liu, Jing Wang, Hongmei Zhao
BACKGROUND:IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet–induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk
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Clot or Not? Reviewing the Reciprocal Regulation Between Lipids and Blood Clotting Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-18 Ziyu Zhang, Maya Rodriguez, Ze Zheng
Both hyperlipidemia and thrombosis contribute to the risks of atherosclerotic cardiovascular diseases, which are the leading cause of death and reduced quality of life in survivors worldwide. The accumulation of lipid-rich plaques on arterial walls eventually leads to the rupture or erosion of vulnerable lesions, triggering excessive blood clotting and leading to adverse thrombotic events. Lipoproteins
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Platelets in Hemostasis, Thrombosis, and Inflammation After Major Trauma Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-18 Paul Vulliamy, Paul C. Armstrong
Trauma currently accounts for 10% of the total global burden of disease and over 5 million deaths per year, making it a leading cause of morbidity and mortality worldwide. Although recent advances in early resuscitation have improved early survival from critical injury, the mortality rate in patients with major hemorrhage approaches 50% even in mature trauma systems. A major determinant of clinical
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Reflections on Belonging: ATVB Membership Committee Perspective Arterioscler. Thromb. Vasc. Biol. (IF 8.7) Pub Date : 2024-01-18 Shayan Mohammadmoradi, Jeffrey J. Hsu, Anberitha T. Matthews
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