title: Improving cardiovascular outcomes in rheumatic diseases: therapeutic potential of circulating endothelial progenitor cells.
abstract: Patients with Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) have a significantly increased risk of cardiovascular disease (CVD). The reason for this is unclear but may be due, at least in part, to the failure of endothelial repair mechanisms. Over the last 15 years there has been much interest in the mechanisms of endothelial renewal and its potential as a therapy for CVD. In the circulation there are two distinct populations of cells; myeloid angiogenic cells (MACs) which augment repair by the paracrine secretion of angiogenic factors, and outgrowth endothelial cells (OECs) which are true endothelial progenitor cells (EPCs) and promote vasculogenesis by differentiating into mature endothelium. There are marked abnormalities in the number and function of these cells in patients with RA and SLE. Inflammatory cytokines including interferon-alpha (IFNα) and tumour-necrosis factor alpha (TNFα) both impair MAC and OEC function ex vivo and may therefore contribute to the CVD risk in these patients. Whilst administration of mononuclear cells, MACs and other progenitors has improved cardiovascular outcomes in the acute setting, this is not a viable option in chronic disease. The pharmacological manipulation of MAC/OEC function in vivo however has the potential to significantly improve endothelial repair and thus reduce CVD in this high risk population.
authors: Arthritis Research UK Epidemiology Unit, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK. Electronic address: John.reynolds@manchester.ac.
authors: John A
authors: JA
authors: Reynolds
authors: Institute of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, UK.
authors: Abigail C
authors: AC
authors: Robertson
authors: Arthritis Research UK Epidemiology Unit, Institute of Inflammation and Repair, Manchester Academic Health Sciences Centre, The University of Manchester, Manchester, UK; NIHR Manchester Musculoskeletal Biomedical Research Unit, and Kellgren Centre for Rheumatology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors: Ian N
authors: IN
authors: Bruce
authors: Institute of Cardiovascular Sciences, Manchester Academic Health Sciences Centre, The University of Manchester, UK; Healthcare Science Research Institute, Manchester Metropolitan University, UK Healthcare Science Research Institute, Manchester Metropolitan University, UK.
authors: M Yvonne
authors: MY
authors: Alexander
mesh_terms: D042501:Angiogenic Proteins / Q000097:blood; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000628:therapy*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D012038:Regeneration; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D042501:Angiogenic Proteins; D002317:Cardiovascular Agents; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators
keywords: Endothelial progenitor cells; Myeloid angiogenic cells; Outgrowth endothelial cells; Rheumatoid Arthritis; Systemic Lupus Erythematosus; Vascular repair