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

Lunde, Ngoc Nguyen ; Gregersen, Ida ; Ueland, Thor ; Shetelig, Christian ; Holm, Sverre ; Kong, Xiang Yi ; Michelsen, Annika E. ; Otterdal, Kari ; Yndestad, Arne and Broch, Kaspar , et al. (2020) In Atherosclerosis 296. p.74-82
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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular disease, Legumain, Macrophage, Plaque modification, Platelets, Protease
in
Atherosclerosis
volume
296
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:31870625
  • scopus:85076845246
ISSN
0021-9150
DOI
10.1016/j.atherosclerosis.2019.12.008
language
English
LU publication?
yes
id
f68ecea1-baac-4af3-9bf5-1a819ae659a6
date added to LUP
2020-01-10 15:32:17
date last changed
2024-05-15 04:30:11
@article{f68ecea1-baac-4af3-9bf5-1a819ae659a6,
  abstract     = {{<p>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.</p>}},
  author       = {{Lunde, Ngoc Nguyen and Gregersen, Ida and Ueland, Thor and Shetelig, Christian and Holm, Sverre and Kong, Xiang Yi and Michelsen, Annika E. and Otterdal, Kari and Yndestad, Arne and Broch, Kaspar and Gullestad, Lars and Nyman, Tuula A. and Bendz, Bjørn and Eritsland, Jan and Hoffmann, Pavel and Skagen, Karolina and Gonçalves, Isabel and Nilsson, Jan and Grenegård, Magnus and Poreba, Marcin and Drag, Marcin and Seljeflot, Ingebjørg and Sporsheim, Bjørnar and Espevik, Terje and Skjelland, Mona and Johansen, Harald Thidemann and Solberg, Rigmor and Aukrust, Pål and Björkbacka, Harry and Andersen, Geir Øystein and Halvorsen, Bente}},
  issn         = {{0021-9150}},
  keywords     = {{Cardiovascular disease; Legumain; Macrophage; Plaque modification; Platelets; Protease}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{74--82}},
  publisher    = {{Elsevier}},
  series       = {{Atherosclerosis}},
  title        = {{Legumain is upregulated in acute cardiovascular events and associated with improved outcome - potentially related to anti-inflammatory effects on macrophages}},
  url          = {{http://dx.doi.org/10.1016/j.atherosclerosis.2019.12.008}},
  doi          = {{10.1016/j.atherosclerosis.2019.12.008}},
  volume       = {{296}},
  year         = {{2020}},
}