Background: Angiopoietin (Ang)-1 and Ang-2, and their shared receptor Tie2, are expressed in rheumatoid arthritis (RA) synovial tissue, but the cellular targets of Ang signalling and the relative contributions of Ang-1 and Ang-2 to arthritis are poorly understood.
Objectives: To determine the cellular targets of Ang signalling in RA synovial tissue, and the effects of Ang-2 neutralisation in murine collagen-induced arthritis (CIA).
Methods: RA and psoriatic arthritis (PsA) synovial biopsies were examined for expression of Tie2 and activated phospho (p)-Tie2 by quantitative immunohistochemistry and immunofluorescent double staining. Human monocyte and macrophage Tie2 expression was determined by flow cytometry and quantitative PCR. Regulation of macrophage intracellular signalling pathways and gene expression were examined by immunoblotting and ELISA. CIA was assessed in mice treated with saline, control antibody, prednisolone or neutralising anti-Ang-2 antibody.
Results: Expression of synovial Tie2 and p-Tie2 was similar in RA and PsA. Tie2 activation in RA patient synovial tissue was predominantly localised in synovial macrophages and was expressed by human macrophage. Ang-1 and Ang-2 stimulated activation of multiple intracellular signalling pathways, and cooperated with tumour necrosis factor to induce macrophage interleukin 6 and macrophage inflammatory protein 1α production. Ang-2 selectively suppressed macrophage thrombospondin-2 production. Ang-2 neutralisation significantly decreased disease severity, synovial inflammation, neo-vascularisation and joint destruction in established CIA.
Conclusions: The authors identify synovial macrophages as primary targets of Ang signalling in RA, and demonstrate that Ang-2 promotes the pro-inflammatory activation of human macrophages. Ang-2 makes requisite contributions to pathology in CIA, indicating that targeting Ang-2 may be of therapeutic benefit in the treatment of RA.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1136/annrheumdis-2011-200718 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Changes in Aqueous Angiopoietin-1/2 Concentrations During the Induction Phase of Intravitreal Faricimab Injections for Diabetic Macular Edema.
Transl Vis Sci Technol
December 2024
Kawasaki-Tama Eye Clinic, Kawasaki, Kanagawa, Japan.
Purpose: The purpose of this study was to investigate the dynamic changes in aqueous concentrations of angiopoietin (Ang)-1/2 and vascular endothelial growth factor (VEGF) during injection in treatment-naïve patients with diabetic macular edema (DME) receiving faricimab during the induction phase (3 consecutive monthly doses) and retrospectively analyze the data.
Methods: Thirty-five eyes of 26 patients (age = 63.1 ± 12.
Emerging clinical evidence of a dual role for Ang-2 and VEGF-A blockade with faricimab in retinal diseases.
Graefes Arch Clin Exp Ophthalmol
December 2024
Doheny Eye Institute, University of California, Los Angeles, 150 N. Orange Grove Blvd, Suite 232, Pasadena, CA, USA.
Anti-vascular endothelial growth factor (VEGF) therapies have transformed the treatment of retinal diseases. However, VEGF signaling is only one component of the complex, multifactorial pathophysiology of retinal diseases, and many patients have residual disease activity despite ongoing anti-VEGF treatment. The angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor receptor-2 (Ang/Tie2) signaling pathway is critical to endothelial cell homeostasis, survival, integrity, and vascular stability.
View Article and Find Full Text PDFEvaluation of the metabolic activity, angiogenic impacts, and GSK-3β signaling of the synthetic cannabinoid MMB-2201 on human cerebral microvascular endothelial cells.
J Cannabis Res
December 2024
Department of Anatomy, College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia.
Angiogenesis is an intrinsic physiological process involving the formation of new capillaries from existing ones. Synthetic cannabinoids refer to a class of human-made chemicals that are primarily designed to mimic the effects of delta-9-tetrahydrocannabinol, the primary psychoactive compound in cannabis. Studies investigating the association between synthetic cannabinoids and cellular reactions are limited, and the available scientific evidence is insufficient.
View Article and Find Full Text PDFCharacterizations of angiotensin-converting enzyme-2 (ACE2) peptidase activity.
Arch Biochem Biophys
November 2024
Department of Pharmacology & Physiology, Georgetown University Medical Center, Washington DC 20007, USA. Electronic address:
Angiotensin (Ang) II (1-8) is a potent vasoconstrictor known for its role in hypertension. Angiotensin-converting enzyme (ACE2) converts Ang II (1-8) to a vasodilator Ang (1-7) by removing the carboxy-terminal Phe. ACE2 more recently gained attention as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the coronavirus disease 2019 (COVID-19) pandemic.
View Article and Find Full Text PDFThe Angiopoietin-Tie-2 Axis in Children and Young Adults with Dengue Virus Infection in the Philippines.
Am J Trop Med Hyg
October 2024
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
Dengue virus (DENV) infection is associated with plasma leakage, which may progress to shock. The angiopoietin (Ang)-tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (Tie-2) axis regulates endothelial permeability. We examined the clinical utility of Ang-1, Ang-2, and the Ang-2-to-Ang-1 ratio for prediction of progression to severe DENV in a prospective cohort study of children and young adults (age 1 to <26 years) with DENV infection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!