Neutrophil extracellular traps (NETs) promote inflammation and atherosclerosis progression. NETs are increased in diabetes and impair the resolution of inflammation during wound healing. Atherosclerosis resolution, a process resembling wound healing, is also impaired in diabetes. Thus, we hypothesized that NETs impede atherosclerosis resolution in diabetes by increasing plaque inflammation. Indeed, transcriptomic profiling of plaque macrophages from NET+ and NET- areas in low-density lipoprotein receptor-deficient (Ldlr-/-) mice revealed inflammasome and glycolysis pathway upregulation, indicating a heightened inflammatory phenotype. We found that NETs declined during atherosclerosis resolution, which was induced by reducing hyperlipidemia in nondiabetic mice, but they persisted in diabetes, exacerbating macrophage inflammation and impairing resolution. In diabetic mice, deoxyribonuclease 1 treatment reduced plaque NET content and macrophage inflammation, promoting atherosclerosis resolution after lipid lowering. Given that humans with diabetes also exhibit impaired atherosclerosis resolution with lipid lowering, these data suggest that NETs contribute to the increased cardiovascular disease risk in this population and are a potential therapeutic target.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205252 | PMC |
| http://dx.doi.org/10.1172/jci.insight.134796 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Identification of Protein Networks and Biological Pathways Driving the Progression of Atherosclerosis in Human Carotid Arteries Through Mass Spectrometry-Based Proteomics.
Int J Mol Sci
December 2024
Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Vulnerable atherosclerotic plaques, especially hemorrhaged lesions, are the major cause of mortalities related to vascular pathologies. The early identification of vulnerable plaques helps to stratify patients at risk of developing acute vascular events. In this study, proteomics analyses of human carotid artery samples collected from patients with atheromatous plaques and complicated lesions, respectively, as well as from healthy controls were performed.
View Article and Find Full Text PDFIntegrated Single-Cell Analysis Revealed Novel Subpopulations of Foamy Macrophages in Human Atherosclerotic Plaques.
Biomolecules
December 2024
State Key Laboratory of Transvascular Implantation Devices, Heart Regeneration and Repair Key Laboratory of Zhejiang Province, Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
Foam cell formation is a hallmark of atherosclerosis, yet the cellular complexity within foam cells in human plaques remains unexplored. Here, we integrate published single-cell RNA-sequencing, spatial transcriptomic, and chromatin accessibility sequencing datasets of human atherosclerotic lesions across eight distinct studies. Through this large-scale integration of patient-derived information, we identified foamy macrophages enriched for genes characteristic of the foamy signature.
View Article and Find Full Text PDFCoronary Artery Ectasia in Acute Coronary Syndrome: The Role of Non-vitamin K Antagonist Oral Anticoagulants in Management.
Interv Cardiol
November 2024
Cardiology Section, Internal Medicine Department, Arab Medical Center Amman, Jordan.
Coronary artery ectasia (CAE) is an abnormal dilatation of coronary artery segments, often linked with atherosclerosis. This report discusses two cases of CAE presenting as acute coronary syndrome. A 36-year-old man had proximal blockage in the left circumflex artery (LCx) and ectasia in the obtuse marginal artery and left anterior descending artery (LAD), while a 53-year-old male smoker had an ectatic LAD with a substantial thrombus.
View Article and Find Full Text PDFPredicting Plaque Regression Based on Plaque Characteristics Identified by Optical Coherence Tomography: A Retrospective Study.
Photodiagnosis Photodyn Ther
January 2025
Department of Cardiology, Shanghai East Hospital of Clinical Medical College, Nanjing Medical University, Nanjing 211166, China; Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:
Background: Atherosclerosis is a lipid-driven, systemic immune-inflammatory disease characterized by the accumulation of plaque within the arterial walls. Plaque regression can occur following appropriate treatment interventions. Optical coherence tomography (OCT), a high-resolution imaging modality, is frequently employed to assess plaque morphology.
View Article and Find Full Text PDFMany strokes from a single non-stenosing plaque: from the last event a light to the first one?
Neurol Sci
January 2025
Neuroradiology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Via Amendola 2, Reggio Emilia, 42122, Italy.
Introduction: Large artery atherosclerosis is a relevant cause of ischemic stroke. Beyond carotid artery stenosis ≥ 50%, causative in etiological classification of stroke, non-stenosing plaques are an increasingly reported cause of stroke with embolic pattern.
Methods: We are presenting the case of a 56 years old woman presenting with a first symptomatic multifocal ischemic stroke in the right internal carotid artery (ICA) territory on 2018 and a finding of asymptomatic past vascular injury in the same vascular territory on neuroimaging studies.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!