Fig. 2

Schematic illustration of the pathogenesis of cardiovascular disease in rheumatoid arthritis. Levels of peripheral endothelial progenitor cells (EPCs) in RA are inhibited compared with general population, which could trigger the endothelial dysfunction (ED). C-reactive protein (CRP) can inhibit EPCs’ differentiation, survival, and function, which further leads to ED. The endothelial-activating cytokines presumably synovitis-derived, including interleukins (IL)-6 and necrosis factor inhibitors (TNF)-α, play important roles in endothelial damage since they inhibit the production of nitric oxide (NO), which, in turn, are responsible for maintaining a healthy endothelium. In addition, RA susceptibility genes human leucocyte antigen (HLA)-DRB1*04 and anti-citrullinated protein antibodies (ACPA) positivity also can contribute to ED. The endothelium plays a central role in atherosclerosis because it produces vasoactive substances including NO that act on the vascular tone and affects homeostasis between the circulating blood cells and the vessel wall. All of these factors, coupled with traditional risk factors for CVD such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, may underlie pro-atherogenic and pro-thrombotic changes, the promotion of cardiac remodeling, alterations in lipid blood profiles, and changes to the morphology of red blood cells, which favor accelerated development of CVD in patients with RA