1. Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages.
- Author
-
Lunde NN, Gregersen I, Ueland T, Shetelig C, Holm S, Kong XY, Michelsen AE, Otterdal K, Yndestad A, Broch K, Gullestad L, Nyman TA, Bendz B, Eritsland J, Hoffmann P, Skagen K, Gonçalves I, Nilsson J, Grenegård M, Poreba M, Drag M, Seljeflot I, Sporsheim B, Espevik T, Skjelland M, Johansen HT, Solberg R, Aukrust P, Björkbacka H, Andersen GØ, and Halvorsen B
- Subjects
- 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, Cardiovascular Diseases metabolism, Cysteine Endopeptidases biosynthesis, Macrophages enzymology, ST Elevation Myocardial Infarction blood
- Abstract
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.)
- Published
- 2020
- Full Text
- View/download PDF