Endothelial cell phenotypes in the rheumatoid synovium: activated, angiogenic, apoptotic and leaky.
Endothelial cells are active participants in chronic inflammatory diseases. These cells undergo phenotypic changes that can be characterised as activated, angiogenic, apoptotic and leaky. In the present review, these phenotypes are described in the context of human rheumatoid arthritis as the disease example. Endothelial cells become activated in rheumatoid arthritis pathophysiology, expressing adhesion molecules and presenting chemokines, leading to leukocyte migration from the blood into the tissue. Endothelial cell permeability increases, leading to oedema formation and swelling of the joints. These cells proliferate as part of the angiogenic response and there is also a net increase in the turnover of endothelial cells since the number of apoptotic endothelial cells increases. The endothelium expresses various cytokines, cytokine receptors and proteases that are involved in angiogenesis, proliferation and tissue degradation. Associated with these mechanisms is a change in the spectrum of genes expressed, some of which are relatively endothelial specific and others are widely expressed by other cells in the synovium. Better knowledge of molecular and functional changes occurring in endothelial cells during chronic inflammation may lead to the development of endothelium-targeted therapies for rheumatoid arthritis and other chronic inflammatory diseases.
Middleton
Jim
J
Endocube S,A,S, Prologue Biotech, Labege cedex, France. jim.middleton@rjah.nhs.uk
Americh
Laure
L
Gayon
Regis
R
Julien
Denis
D
Aguilar
Luc
L
Amalric
Francois
F
Girard
Jean-Philippe
JP
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000473:pathology; D002463:Cell Membrane Permeability / Q000235:genetics*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010641:Phenotype; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*