1. Soluble VE-cadherin in rheumatoid arthritis patients correlates with disease activity: evidence for tumor necrosis factor α-induced VE-cadherin cleavage
- Author
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Danielle Gulino-Debrac, Mary Jan, Isabelle Vilgrain, Olivier Vittecoq, Laurence Bouillet, Tiphaine Mannic, Xavier Le Loët, Mariela Subileau, Mélanie Arboleas, Adama Sidibé, and Thibault Vandhuick
- Subjects
Adult ,Male ,Time Factors ,Angiogenesis ,Immunology ,Arthritis ,Protein tyrosine phosphatase ,Transfection ,Arthritis, Rheumatoid ,chemistry.chemical_compound ,Rheumatology ,Antigens, CD ,Human Umbilical Vein Endothelial Cells ,Immunology and Allergy ,Medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,RNA, Small Interfering ,Cells, Cultured ,Aged ,business.industry ,Tumor Necrosis Factor-alpha ,Tyrosine phosphorylation ,Middle Aged ,medicine.disease ,Cadherins ,Recombinant Proteins ,src-Family Kinases ,chemistry ,Culture Media, Conditioned ,Gene Knockdown Techniques ,Cancer research ,Tumor necrosis factor alpha ,Female ,RNA Interference ,VE-cadherin ,business ,Tyrosine kinase ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Objective Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that principally attacks synovial joints. However, accelerated atherosclerosis and increased cardiovascular morbidity and mortality are major clinical consequences of endothelial dysfunction in RA patients. Tumor necrosis factor α (TNFα) is the major mediator of inflammation in RA, related to vascular injury by targeting VE-cadherin, an endothelium-specific adhesion molecule of vital importance for endothelium integrity and angiogenesis. We undertook this study to examine the mechanisms regulating VE-cadherin processing by TNFα and their occurrence in RA. Methods Human umbilical vein endothelial cells were used in primary culture and treated with recombinant TNFα to study VE-cadherin cleavage. Cell lysates and conditioned media were analyzed by Western blotting for VE-cadherin cytoplasmic domain and extracellular domain (VE-90) generation, respectively. VE-90 was analyzed at baseline and at the 1-year followup in sera from 63 RA patients (from the Very Early Rheumatoid Arthritis cohort) with disease duration of
- Published
- 2011