Glucocorticoid induced TNF receptor family-related protein (GITR) – A novel driver of atherosclerosis

Research output: Contribution to journalReview article

Abstract

Atherosclerosis is a lipid-driven, chronic inflammatory disease. In spite of efficient lipid lowering treatments, such as statins and PCSK9 inhibitors, patients, especially those with elevated inflammatory biomarkers, still have a significant residual cardiovascular disease risk. Novel drugs targeting inflammatory mediators are needed to further reduce this residual risk. Agonistic immune checkpoint proteins, including CD86, CD40L and CD40, have been shown to be drivers of atherosclerosis. Recently, glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR), a co-stimulatory immune checkpoint protein, was identified to be pivotal in cardiovascular disease. Cardiovascular patients have elevated soluble GITR plasma levels compared to healthy controls. Furthermore, in human carotid endarterectomy plaques, GITR expression was higher in plaques from symptomatic compared to asymptomatic patients and correlated with features of plaque vulnerability. Moreover, depleting GITR reduced atherosclerotic plaque development in mice. GITR-deficient monocytes and macrophages exhibited less inflammatory potential and reduced migratory capacity. In this review, we discuss GITR's effects on various immune cells, mechanisms, signalling pathways and finally GITR's potential as a novel drug target in atherosclerosis.

Details

Authors
Organisations
External organisations
  • Academic Medical Center of University of Amsterdam (AMC)
  • German Centre for Cardiovascular Research
  • Ludwig-Maximilian University of Munich
  • Munich Cluster for Systems Neurology
  • Maastricht University Medical Centre
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cardiac and Cardiovascular Systems

Keywords

  • Atherosclerosis, Costimulatory molecule, CVD, GITR, Immune checkpoint
Original languageEnglish
Article number106884
JournalVascular Pharmacology
Volume139
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes