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Abstract

60 COX = cyclooxygenase; CRH = corticotropin-releasing hormone; FGF = fibroblast growth factor; HEV = high endothelial venules; HGF = hepatocyte growth factor; ICAM = intercellular adhesion molecule; IL = interleukin; IFN = interferon; MCP-1 = monocyte chemoattractant protein-1; MHC = major histocompatibility complex; MMP = matrix metalloproteinase; OA = osteoarthritic; RA = rheumatoid arthritis; TIMP = tissue inhibitor of metalloproteinase; TNF = tumour necrosis factor; VCAM = vascular cell adhesion molecule; VEGF = vascular endothelial growth factor. Arthritis Research & TherapyVol 6 No 2 Middleton et al. IntroductionRheumatoid arthritis (RA) is a chronic, systemic inflammatory disease affecting the joints, and is associated with increased morbidity and mortality [1][2][3]. The synovium or synovial membrane, which surrounds the joint cavity, becomes massively hypertrophied in RA. This tissue, known as pannus, can become invasive, penetrating and degrading the cartilage and bone, resulting in joint deformities, in functional deterioration and in profound disability.The lining layer, or intima, of the synovium is normally one to three cells thick and it comprises macrophage-like cells and fibroblast-like cells [4]. This layer undergoes thickening and hypertrophy in RA, largely due to the increased recruitment of monocytes from the blood supply in the deeper layer, or subintima, of the tissue [5,6]. Other inflammatory cells such as T cells (mainly CD45RO) and B lymphocytes migrate from the blood into the synovium and can form ectopic lymphoid follicles around blood vessels. These structures resemble the lymphoid follicles of lymph nodes. In addition, neutrophils migrate into the synovium and end up in large numbers in the synovial joint fluid. The role of endothelial cells in RA AbstractEndothelial 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...

Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on HIFs and angiogenesis in RA

“…Failure to form functional mature vessels is known to contribute to oedema formation, swelling and inflammation in RA joints (reviewed in [55]). Interestingly, recent work in angptl-4 -deficient mice has shown that ANGPTL-4 is important in vessel maturation because mice lacking ANGPTL-4 exhibited disruption of endothelial adherens junctions and pericyte coverage, with impaired angiogenesis and vascular leakage as a result [56,57].…”

Determination of the Diagnostic Values of Asymmetric Dimethylarginine as an Indicator for Evaluation of the Endothelial Dysfunction in Patients with Rheumatoid Arthritis

“…(4) Third possibility is that the inflammatory synovia in RA is with increased proliferation and potent apoptosis of the vascular endothelial cells [25]. The cultivated endothelial cells liberate more ADMA than SDMA [26].…”

Asymmetric Dimethyl Arginine as a Biomarker of Atherosclerosis in Rheumatoid Arthritis

“…Moreover, other posttranslational modifications of LDL may also account for NO uncoupling [ 34 ]. In the rheumatoid synovia, endothelial cells undergo a phenotypic change characterized by an increase in activation, angiogenesis, and apoptosis [ 35 ]. The increased turnover of endothelial cells as well as the increased number of proliferating cells associated with angiogenetic microenvironment of the inflamed joint may be a source of methylarginines.…”