Inflammation, vascular injury and repair in rheumatoid arthritis

Abstract

The systemic pro-inflammatory state present in patients with rheumatoid arthritis (RA) accelerates the progression of atherosclerosis through chronic endothelial activation. Uncoupling of endothelial nitric oxide synthase plays a central role in the amplification of oxidative signalling pathways that chronically activate and, ultimately, injure the endothelium. Recent studies indicate that the resultant loss of endothelial integrity in patients with RA may also involve defects in the vascular regenerative potential provided by circulating endothelial progenitor cells (EPC). This is most likely the consequence of endothelial cell dysfunction in the bone marrow stroma, which hampers the mobilisation of these EPC to the circulation. In addition, mediators of systemic inflammation in RA can affect a second pathway of vascular regeneration. Under normal circumstances, myeloid CD14+ cells can adopt a pro-angiogenic phenotype that plays a key role in vascular remodelling and collateral formation. However, the chronic systemic inflammation observed in patients with RA may skew the differentiation of bone marrow and circulating CD14+ cells in such a way that these cells lose their capacity to support collateral formation, increasing the risk of cardiovascular disease. Taken together, in patients with RA, the impaired capacity of circulating cells to support vascular regeneration may comprise a novel pathway in the development of premature atherosclerosis.

Anti-tumor necrosis factor-α therapy and changes of flow-mediated vasodilatation in psoriatic and rheumatoid arthritis patients

“…Several studies report that there is higher cardiovascular morbidity and mortality in the patients affected by autoimmune arthritis compared to the general population [17][18][19][20][21][22][23][24]. The articular inflammation causes an overexpression of mediators such as articular and systemic proinflammatory cytokines.…”

“…TNF-a is a strong proinflammatory cytokine that causes neutrophilic chemotaxis, macrophage activation, and increased superoxide production. All of these may cause endothelial disorder and atherogenesis [17][18][19][20][21][22][23][24]. Endothelium normally reduces these processes through the NO benefits, therefore, the endothelial dysfunction is recognized as an atherosclerosis precursor [25,26] and as a ''barometer'' of the cardiovascular functionality [27].…”

The Assessment of Serum Endocan Levels in Children With Juvenile Idiopathic Arthritis

“…15 The most important factors in the pathogenesis of cardiovascular disease in patients with RA are endothelial dysfunction and vessel wall damage. 16 It has been speculated that cardiovascular complications seen in patients with JIA start with vascular damage years before symptoms present. 17 Accordingly, a recent study revealed that subclinical cardiovascular changes tended to present earlier, particularly in obese individuals.…”

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

“…In rheumatoid arthritis, this risk approaches the risk of patients with diabetes 36. The pathogenesis of this increased risk is largely enigmatic, but is proposed to arise from a chronic inflammatory environment, causing vascular damage and plaque formation 37 38. The occurrence of atherosclerotic plaques has been related to an increasing chronological age 11.…”