Accelerated atherogenesis in autoimmune rheumatic diseases.
The observation that systemic inflammatory rheumatic diseases such as rheumatoid arthritis (RA) are associated with a significantly increased rate of cardiovascular disease, which often occurs at a younger age than in the normal population, is particularly important given the increasing interest in the role of inflammation in atherogenesis in the general population. This review examines the accumulating evidence for accelerated atherogenesis of RA and updates the hypothesis that vasculitis plays a major role in this. Endothelial dysfunction (ECD), widely regarded as initial lesion in atherogenesis, has been shown to occur commonly in primary vasculitis. This ECD is a diffuse event, demonstrable in more than one vascular bed. It is not simply due to scarring in the vessel wall, related to the focal inflammation of the underlying vasculitis, since it may be reversed by suppression of the immune inflammation. However, the mechanisms for this ECD differ from that of the primary vasculitis. Preliminary evidence suggests that inflammatory mediators such as CRP, TNF, or sphingolipids may be involved. The diffuse ECD of vasculitis may have important consequences for both the progression of the primary disease and for cardiovascular events. A model for the role of vasculitis-induced ECD in the accelerated atherogenesis of rheumatic diseases is presented. These concepts are discussed together with the messages they suggest for 'idiopathic' atherosclerosis in the general population.
Bacon
P A
PA
Department of Rheumatology, Division of Immunity and Infection, University of Birmingham, Birmingham B22 2TT, UK. p.a.bacon@bham.ac.uk
Stevens
R J
RJ
Carruthers
D M
DM
Young
S P
SP
Kitas
G D
GD
D001161:Arteriosclerosis / Q000209:etiology*; D001172:Arthritis, Rheumatoid / Q000150:complications; D001327:Autoimmune Diseases / Q000150:complications*; D002097:C-Reactive Protein / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006331:Heart Diseases / Q000209:etiology; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000209:etiology; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008955:Models, Cardiovascular; D012216:Rheumatic Diseases / Q000150:complications*; D013107:Sphingolipids / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014657:Vasculitis / Q000209:etiology
D013107:Sphingolipids; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein