A5040020632- Atherosclerosis and Cardiovascular Diseases
- Cerebrovascular and Carotid Artery Diseases
- Lipoproteins and Cardiovascular Health
- Protease and Inhibitor Mechanisms
- Cardiovascular Health and Disease Prevention
- RNA modifications and cancer
- Coronary Interventions and Diagnostics
- Cancer-related molecular mechanisms research
- Cell Adhesion Molecules Research
- Cardiovascular Disease and Adiposity
- Connective tissue disorders research
- RNA Research and Splicing
- Galectins and Cancer Biology
- Parathyroid Disorders and Treatments
- Genetic Associations and Epidemiology
- Aortic aneurysm repair treatments
- Bioinformatics and Genomic Networks
- Adipokines, Inflammation, and Metabolic Diseases
- MicroRNA in disease regulation
- Erythrocyte Function and Pathophysiology
- Aortic Disease and Treatment Approaches
- Blood properties and coagulation
- Circular RNAs in diseases
- Lipid metabolism and disorders
- Extracellular vesicles in disease
Karolinska Institutet
2016-2025
Karolinska University Hospital
2016-2025
Severance Hospital
2023
Yonsei University
2023
Ewha Womans University
2023
Technical University of Munich
2017
University of Ottawa
2017
University Health Network
2017
University of Toronto
2017
Science for Life Laboratory
2016
Background: The majority of the human genome comprises noncoding sequences, which are in part transcribed as long RNAs (lncRNAs). lncRNAs exhibit multiple functions, including epigenetic control gene expression. In this study, effect lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) on atherosclerosis was examined. Methods: determined apolipoprotein E–deficient (Apoe − /− ) MALAT1-deficient (Malat1 −/− mice that were fed with a high-fat diet and by studying regulation...
Objective— During inflammation, macrophages secrete vesicles carrying RNA, protein, and lipids as a form of extracellular communication. In the vessel wall, (EVs) have been shown to be transferred between vascular cells during atherosclerosis; however, role macrophage-derived EVs in atherogenesis is not known. Here, we hypothesize that atherogenic microRNAs (miRNAs) mediate cell–cell communication promote proinflammatory proatherogenic phenotypes recipient cells. Approach Results— We...
The identification of patients with high-risk atherosclerotic plaques prior to the manifestation clinical events remains challenging. Recent findings question histology- and imaging-based definitions "vulnerable plaque," necessitating an improved approach for predicting onset symptoms.We performed a proteomics comparison vascular extracellular matrix associated molecules in human carotid endarterectomy specimens from 6 symptomatic versus asymptomatic identify protein signature plaques....
Identification and treatment of the rupture prone atherosclerotic plaque remains a challenge for reducing burden cardiovascular disease. The interconnection metabolic inflammatory processes in plaques is poorly understood. Herein, we investigate associations between metabolite profiles, mediators vulnerability carotid plaques.We collected 159 from patients undergoing endarterectomy measured 165 different metabolites targeted metabolomics approach. We identified profile that associated with...
Background: Chronic activation of the innate immune system drives inflammation and contributes directly to atherosclerosis. We previously showed that macrophages in atherogenic plaque undergo RIPK3 (receptor-interacting serine/threonine-protein kinase 3)-MLKL (mixed lineage domain-like protein)–dependent programmed necroptosis response sterile ligands such as oxidized low-density lipoprotein damage-associated molecular patterns is active advanced atherosclerotic plaques. Upstream RIPK3-MLKL...
In the search for markers and modulators of vascular disease, microRNAs (miRNAs) have emerged as potent therapeutic targets.To investigate miRNAs clinical interest in patients with unstable carotid stenosis at risk stroke.Using patient material from BiKE (Biobank Karolinska Endarterectomies), we profiled miRNA expression stable versus plaque. A polymerase chain reaction-based array plasma, sampled lesion site, identified 8 deregulated (miR-15b, miR-29c, miR-30c/d, miR-150, miR-191, miR-210,...
Long noncoding RNAs (lncRNAs) are important regulators of biological processes involved in vascular tissue homeostasis and disease development. The present study assessed the functional contribution lncRNA myocardial infarction-associated transcript (MIAT) to atherosclerosis carotid artery disease. We profiled differences RNA expression patients with advanced atherosclerotic lesions from Biobank Karolinska Endarterectomies. MIAT was identified as most upregulated plaques compared...
Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While link systemic atherosclerosis is well established, implications altered in artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition pyruvate (PDH) has been identified as major metabolic step regulating inflammation. Whether PDK/PDH axis plays role vascular inflammation atherosclerotic cardiovascular disease remains unclear.
Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing plaque stability.Muscle contraction, muscle development, and actin cytoskeleton were most pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) microarrays from human carotid plaques (n=177)...
Atherosclerosis is a chronic inflammatory disease that driven, in part, by activation of vascular endothelial cells (ECs). In response to stimuli, the nuclear factor kappa-light-chain-enhancer activated B (NF-κB) signaling pathway orchestrates expression network EC genes contribute monocyte recruitment and diapedesis across endothelium. Although many long noncoding RNAs (lncRNAs) are dysregulated atherosclerosis, they remain poorly characterized, especially context human inflammation. Prior...
Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human approaches. We previously identified the transcription factor TCF21 as causal CAD gene at 6q23.2 characterized its downstream transcriptional network is enriched for GWAS genes. Here we investigate hypothesis interacts a target gene, aryl hydrocarbon receptor (AHR),...
Background: Atherosclerosis progression is modulated by interactions with the adaptive immune system. Humoral immunity can help protect against atherosclerosis formation; however, existence, origin, and function of putative atherogenic antibodies are controversial. How such atherosclerosis-promoting could affect specific composition stability plaques, as well vasculature generally, remains unknown. Methods: We addressed overall contribution to plaque formation, composition, in vivo (1) mice...
Clinical tools to identify individuals with unstable atherosclerotic lesions are required improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis plaques plasma from patients undergoing carotid endarterectomy for stroke was used molecular signatures causal relationship disease. Local collected in the lesion proximity following clamping prior arteriotomy profiled together matched peripheral plasma. This translational workflow identified biliverdin...
Abstract Background The metabolism of tryptophan (Trp) along the kynurenine pathway has been shown to carry strong immunoregulatory properties. Several experimental studies indicate that this is a major regulator vascular inflammation and influences atherogenesis. Knowledge role in human atherosclerosis remains incomplete. Objectives In study, we performed multiplatform analysis tissue samples, vitro vivo functional assays elucidate potential atherosclerosis. Methods results Comparison...
PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation human atherosclerotic plaques associated smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens.Here, applied systems biology approach to gain deeper insights into the role normal diseased vessel wall.Genetic analyses revealed association of intronic variant rs1531817 maximum internal carotid intima-media...
The E3-ligase CBL-B (Casitas B-cell lymphoma-B) is an important negative regulator of T cell activation that also expressed in macrophages. cells and macrophages mediate atherosclerosis, but their regulation this disease remains largely unknown; thus, we studied the function atherogenesis.The expression human atherosclerotic plaques was lower advanced lesions compared with initial correlated inversely necrotic core area. Twenty weeks old Cblb-/-Apoe-/- mice showed a significant increase...
Abstract Aims Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is a major cause death disability. While plaque burden predictor adverse outcomes, vulnerability increasingly recognized as driver lesion rupture risk for clinical events. Defining molecular regulators carotid instability could inform development new biomarkers and/or translational targets at-risk individuals. Methods results Using two independent human endarterectomy biobanks, we found that...