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Inflammation, vascular injury and repair in rheumatoid arthritis
  1. A J van Zonneveld,
  2. H C de Boer,
  3. E P van der Veer,
  4. T J Rabelink
  1. Department of Nephrology and the Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence to Dr A J van Zonneveld, Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; a.j.vanzonneveld{at}


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.

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  • Competing interests None.

  • Provenance and Peer review Not commissioned; externally peer reviewed.