Depletion of Endothelial Progenitor Cells in the Peripheral Blood of Patients With Rheumatoid Arthritis

Abstract

Background-Rheumatoid arthritis (RA) is characterized by increased cardiovascular morbidity and mortality that cannot be explained solely by traditional cardiovascular risk factors. Cardiovascular morbidity is related to disease activity and can be normalized by effective therapy. Because the quantity of endothelial progenitor cells (EPCs) in the peripheral blood is correlated inversely with cardiovascular risk, we studied whether such abnormalities could also be observed in patients with RA. Methods and Results-EPCs were determined in 52 RA patients and in 16 healthy referents (HRs) by fluorescence-activated cell-sorting (FACS) analysis. Patients were divided into groups characterized by active disease (nϭ36) and low disease activity (nϭ16). Cells that were positive by flow cytometry for CD34/KDR/AC133 within the lymphocyte population were characterized as EPCs. Furthermore, in subgroups of patients, circulating EPCs were also quantified by a colony-forming unit (CFU) and a circulating angiogenic cell (CAC) assay.

Circulating endothelial progenitor cells and depression: a possible novel link between heart and soul

“…20 A further established risk factor recognized today in the pathogenesis of arteriosclerosis and cardiovascular disorders is depression. However, although an association between mood disorders and susceptibility to cardiovascular events has been discovered by several researchers, 2,3,7-12,41-44 and altered circulating EPC levels have been reported in various conditions associated with vascular diseases, [20][21][22][23][24][25] to date no studies have attempted to evaluate the significance of EPCs in patients with major depression. Therefore, we investigated the significance of EPC numbers in our study sample by using flow cytometry and found a significant decrease in both mature (CD34 þ / VEGFR2 þ ) and immature (CD133 þ /VEGFR2 þ ) circulating EPC numbers in depressed patients versus healthy controls, and moreover, a statistically significant inverse relationship between EPC counts and the severity of depression independent of EPC phenotypes (as assessed by BDI scores 33 ).…”

“…This cell population, endothelial progenitor cells (EPCs), appears to be involved in both the maintenance of vascular integrity 14 and postnatal vasculogenesis (for example, tumor vascularization). [15][16][17][18] Since their identification by Asahara et al, 19 several studies have shown reduced numbers and/or impaired function of EPCs in a variety of cardiovascular risk states, including diabetes mellitus, 20 hypercholesterolemia, 21 hypertension, 22 chronic renal failure, 23 rheumatoid arthritis 24 and cigarette smoking. 25 Alternatively, cardiovascular protective factors such as exercise training, 26 statin therapy, 27 angiotensin II receptor antagonists 28 and peroxisome proliferatoractivated receptor agonists 29 are known to increase EPC number and function.…”

Working hypothesis to redefine endothelial progenitor cells

“…Later studies demonstrated that the concentration of CFU-ECs was decreased in patients with type I diabetes, 48 chronic obstructive pulmonary disease, 49 congestive heart failure, 50 and rheumatoid arthritis. 51 However, some studies have contradicted the trend of lower numbers in disease susceptibility; CFU-EC concentration has been shown to be significantly increased in patients with unstable angina, 52 at the time of myocardial infarction (MI), 53 and within 7 days of an acute MI. 54 Thus, evidence points to reduced CFU-EC concentration in patients at risk for vascular disease, and increased during acute cardiovascular stress.…”

In Vitro Hyperglycemia or a Diabetic Intrauterine Environment Reduces Neonatal Endothelial Colony-Forming Cell Numbers and Function

“…Initial studies reported a reduction in circulating EPCs in individuals with coronary artery disease and in those adults with a high cardiovascular disease risk predicted by a Framingham risk factor score (19,20). Interestingly, this paradigm has held for multiple disease states in adults including diabetes, peripheral vascular disease, rheumatoid arthritis, and preeclampsia (21)(22)(23)(24). However, no studies have been reported in infants or children.…”