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

Acute Disease Amino Acid Sequence Blood Platelets / metabolism Cardiovascular Diseases / complications Carotid Artery Diseases / metabolism Cross-Sectional Studies Cysteine Endopeptidases / biosynthesis Cytokines / pharmacology Diabetes Mellitus, Type 2 / blood Follow-Up Studies Humans Lipopolysaccharides / pharmacology Macrophages / enzymology Monocytes / drug effects Percutaneous Coronary Intervention Plaque, Atherosclerotic / chemistry Platelet Activation Recombinant Proteins / pharmacology ST Elevation Myocardial Infarction / blood Sweden / epidemiology THP-1 Cells

Cardiovascular disease Legumain Macrophage Plaque modification Platelets Protease

Journal

Atherosclerosis

ISSN: 1879-1484

Titre abrégé: Atherosclerosis

Pays: Ireland

ID NLM: 0242543

Informations de publication

Date de publication:
03 2020

Historique:

received: 15 04 2019

revised: 20 11 2019

accepted: 12 12 2019

pubmed: 25 12 2019

medline: 16 1 2021

entrez: 25 12 2019

Statut: ppublish

Résumé

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. 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. 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. Our data demonstrate for the first time that legumain is upregulated during acute cardiovascular events and is associated with improved outcome.

Sections du résumé

BACKGROUND AND AIMS

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.

Identifiants

DOI: 10.1016/j.atherosclerosis.2019.12.008 PMID: 31870625

pubmed: 31870625

pii: S0021-9150(19)31626-0

doi: 10.1016/j.atherosclerosis.2019.12.008

pii:

doi:

Substances chimiques

Cytokines 0

Lipopolysaccharides 0

Recombinant Proteins 0

Cysteine Endopeptidases EC 3.4.22.-

asparaginylendopeptidase EC 3.4.22.34

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

74-82

Commentaires et corrections

Type : CommentIn

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.