SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Buerger A.)
 

Sökning: WFRF:(Buerger A.) > Glucocorticoid-indu...

Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans

Shami, Annelie (författare)
University of Amsterdam
Atzler, Dorothee (författare)
German Centre for Cardiovascular Research,German Center for Lung Research (DZL),World Orthopaedic Concern
Bosmans, Laura A. (författare)
Academic Medical Center of University of Amsterdam (AMC)
visa fler...
Winkels, Holger (författare)
German Center for Lung Research (DZL),La Jolla Institute for Allergy and Immunology
Meiler, Svenja (författare)
Academic Medical Center of University of Amsterdam (AMC),German Center for Lung Research (DZL)
Lacy, Michael (författare)
German Centre for Cardiovascular Research,German Center for Lung Research (DZL)
van Tiel, Claudia (författare)
Academic Medical Center of University of Amsterdam (AMC)
Ta Megens, Remco (författare)
Maastricht University Medical Centre,German Center for Lung Research (DZL)
Nitz, Katrin (författare)
German Center for Lung Research (DZL)
Baardman, Jeroen (författare)
Academic Medical Center of University of Amsterdam (AMC)
Kusters, Pascal (författare)
Academic Medical Center of University of Amsterdam (AMC)
Seijkens, Tom (författare)
Academic Medical Center of University of Amsterdam (AMC)
Buerger, Christina (författare)
German Center for Lung Research (DZL)
Janjic, Aleksandar (författare)
World Orthopaedic Concern
Riccardi, Carlo (författare)
University of Perugia
Edsfeldt, Andreas (författare)
Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital
Monaco, Claudia (författare)
Kennedy Institute of Rheumatology
Daemen, Mat (författare)
Academic Medical Center of University of Amsterdam (AMC)
de Winther, Menno P.J. (författare)
Academic Medical Center of University of Amsterdam (AMC),German Center for Lung Research (DZL)
Nilsson, Jan (författare)
Lund University,Lunds universitet,Kardiovaskulär forskning - immunitet och ateroskleros,Forskargrupper vid Lunds universitet,Cardiovascular Research - Immunity and Atherosclerosis,Lund University Research Groups
Weber, Christian (författare)
German Centre for Cardiovascular Research,Maastricht University Medical Centre,German Center for Lung Research (DZL)
Gerdes, Norbert (författare)
University Hospital of Düsseldorf
Gonçalves, Isabel (författare)
Lund University,Lunds universitet,Kardiovaskulär forskning - translationella studier,Forskargrupper vid Lunds universitet,Cardiovascular Research - Translational Studies,Lund University Research Groups,Skåne University Hospital
Lutgens, Esther (författare)
German Center for Lung Research (DZL),Academic Medical Center of University of Amsterdam (AMC),German Centre for Cardiovascular Research
visa färre...
 (creator_code:org_t)
2020-07-30
2020
Engelska 11 s.
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:31, s. 2938-2948
Relaterad länk:
http://dx.doi.org/10... (free)
visa fler...
https://academic.oup...
https://lup.lub.lu.s...
https://doi.org/10.1...
visa färre...
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • AIMS: GITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND RESULTS: GITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular events (n = 100) compared to asymptomatic patients (n = 93) and correlated with parameters of plaque vulnerability, including plaque macrophage, lipid and glycophorin A content, and levels of interleukin (IL)-6, IL-12, and C-C-chemokine ligand 2. Soluble GITR levels were elevated in plasma from subjects with CVD compared to healthy controls. Plaque area in 28-week-old Gitr-/-Apoe-/- mice was reduced, and plaques had a favourable phenotype with less macrophages, a smaller necrotic core and a thicker fibrous cap. GITR deficiency did not affect the lymphoid population. RNA sequencing of Gitr-/-Apoe-/- and Apoe-/- monocytes and macrophages revealed altered pathways of cell migration, activation, and mitochondrial function. Indeed, Gitr-/-Apoe-/- monocytes displayed decreased integrin levels, reduced recruitment to endothelium, and produced less reactive oxygen species. Likewise, GITR-deficient macrophages produced less cytokines and had a reduced migratory capacity. CONCLUSION: Our data reveal a novel role for the immune checkpoint GITR in driving myeloid cell recruitment and activation in atherosclerosis, thereby inducing plaque growth and vulnerability. In humans, elevated GITR expression in carotid plaques is associated with a vulnerable plaque phenotype and adverse cerebrovascular events. GITR has the potential to become a novel therapeutic target in atherosclerosis as it reduces myeloid cell recruitment to the arterial wall and impedes atherosclerosis progression.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Nyckelord

Atherosclerosis
Carotid artery
Co-stimulation
GITR
Monocyte

Publikations- och innehållstyp

art (ämneskategori)
ref (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy