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Legumain is upregulated in acute cardiovascular events and associated with improved outcome – potentially related to anti-inflammatory effects on macrophages
- Publication Year :
- 2020
-
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.
- Subjects :
- Blood Platelets
Carotid Artery Diseases
Lipopolysaccharides
0301 basic medicine
THP-1 Cells
Population
Type 2 diabetes
030204 cardiovascular system & hematology
Legumain
Peripheral blood mononuclear cell
Monocytes
03 medical and health sciences
Percutaneous Coronary Intervention
0302 clinical medicine
Humans
Medicine
VDP::Medisinske Fag: 700
Platelet
Amino Acid Sequence
Platelet activation
education
Sweden
education.field_of_study
biology
business.industry
Macrophages
Platelet Activation
medicine.disease
Plaque, Atherosclerotic
Recombinant Proteins
3. Good health
Cysteine Endopeptidases
Cross-Sectional Studies
030104 developmental biology
Real-time polymerase chain reaction
Diabetes Mellitus, Type 2
Cardiovascular Diseases
Acute Disease
Immunology
biology.protein
Cytokines
ST Elevation Myocardial Infarction
Immunohistochemistry
Cardiology and Cardiovascular Medicine
business
Follow-Up Studies
Subjects
Details
- ISSN :
- 00219150
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....e20ce7e00fc57db5cd79b0e423117451