دورية أكاديمية

Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages.

التفاصيل البيبلوغرافية
العنوان: Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages.
المؤلفون: Lunde NN; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway. Electronic address: n.n.lunde@farmasi.uio.no., Gregersen I; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Ueland T; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway., Shetelig C; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway., Holm S; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Kong XY; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Michelsen AE; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Otterdal K; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Yndestad A; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Broch K; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; KG Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway and Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway., Gullestad L; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway; KG Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway and Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway., Nyman TA; Proteomics Core Facility, Department of Immunology, Institute of Clinical Medicine, University of Oslo and Rikshospitalet Oslo, Oslo, Norway., Bendz B; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway., Eritsland J; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway., Hoffmann P; Section of Interventional Cardiology, Oslo University Hospital Ullevål, Oslo, Norway., Skagen K; Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, Norway., Gonçalves I; Experimental Cardiovascular Research Unit, Dept. of Clinical Sciences, Malmö Lund University, Malmö, Sweden; Department of Cardiology, Skåne University Hospital, Sweden., Nilsson J; Experimental Cardiovascular Research Unit, Dept. of Clinical Sciences, Malmö Lund University, Malmö, Sweden., Grenegård M; School of Medical Sciences, Örebro University, Umeå, Sweden., Poreba M; Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, Poland., Drag M; Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wroclaw, Poland., Seljeflot I; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway., Sporsheim B; Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Espevik T; Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Skjelland M; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, Norway., Johansen HT; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway., Solberg R; Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway., Aukrust P; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway., Björkbacka H; Experimental Cardiovascular Research Unit, Dept. of Clinical Sciences, Malmö Lund University, Malmö, Sweden., Andersen GØ; Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway., Halvorsen B; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
المصدر: Atherosclerosis [Atherosclerosis] 2020 Mar; Vol. 296, pp. 74-82. Date of Electronic Publication: 2019 Dec 14.
نوع المنشور: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Ireland NLM ID: 0242543 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1484 (Electronic) Linking ISSN: 00219150 NLM ISO Abbreviation: Atherosclerosis Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.
مواضيع طبية MeSH: Cardiovascular Diseases/*metabolism , Cysteine Endopeptidases/*biosynthesis , Macrophages/*enzymology , ST Elevation Myocardial Infarction/*blood, Acute Disease ; Amino Acid Sequence ; Blood Platelets/metabolism ; Cardiovascular Diseases/complications ; Cardiovascular Diseases/pathology ; Carotid Artery Diseases/metabolism ; Carotid Artery Diseases/pathology ; Cross-Sectional Studies ; Cysteine Endopeptidases/blood ; Cysteine Endopeptidases/genetics ; Cysteine Endopeptidases/pharmacology ; Cytokines/pharmacology ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/complications ; Follow-Up Studies ; Humans ; Lipopolysaccharides/pharmacology ; Monocytes/drug effects ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic/chemistry ; Platelet Activation ; Recombinant Proteins/pharmacology ; ST Elevation Myocardial Infarction/mortality ; ST Elevation Myocardial Infarction/surgery ; Sweden/epidemiology ; THP-1 Cells
مستخلص: Background and Aims: We have previously found increased levels of the cysteine protease legumain in plasma and plaques from patients with carotid atherosclerosis. This study further investigated legumain during acute cardiovascular events.
Methods: Circulating levels of legumain from patients and legumain released from platelets were assessed by enzyme-linked-immunosorbent assay. Quantitative PCR and immunoblotting were used to study expression, while localization was visualized by immunohistochemistry.
Results: In the SUMMIT Malmö cohort (n = 339 with or without type 2 diabetes and/or cardiovascular disease [CVD], and 64 healthy controls), the levels of circulating legumain were associated with the presence of CVD in non-diabetics, with no relation to outcome. In symptomatic carotid plaques and in samples from both coronary and intracerebral thrombi obtained during acute cardiovascular events, legumain was co-localized with macrophages in the same regions as platelets. In vitro, legumain was shown to be present in and released from platelets upon activation. In addition, THP-1 macrophages exposed to releasate from activated platelets showed increased legumain expression. Interestingly, primary peripheral blood mononuclear cells stimulated with recombinant legumain promoted anti-inflammatory responses. Finally, in a STEMI population (POSTEMI; n = 272), patients had significantly higher circulating legumain before and immediately after percutaneous coronary intervention compared with healthy controls (n = 67), and high levels were associated with improved outcome.
Conclusions: Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.
Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.
(Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
التعليقات: Comment in: Atherosclerosis. 2020 Mar;296:66-67. (PMID: 32014264)
فهرسة مساهمة: Keywords: Cardiovascular disease; Legumain; Macrophage; Plaque modification; Platelets; Protease
المشرفين على المادة: 0 (Cytokines)
0 (Lipopolysaccharides)
0 (Recombinant Proteins)
EC 3.4.22.- (Cysteine Endopeptidases)
EC 3.4.22.34 (asparaginylendopeptidase)
تواريخ الأحداث: Date Created: 20191225 Date Completed: 20210115 Latest Revision: 20210115
رمز التحديث: 20240628
DOI: 10.1016/j.atherosclerosis.2019.12.008
PMID: 31870625
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-1484
DOI:10.1016/j.atherosclerosis.2019.12.008