Suppression of inflammation reduces endothelial microparticles in active systemic lupus erythematosus

Abstract

BackgroundIn a prospective observational study, we investigated whether patients with active systemic lupus erythematosus (SLE) had higher indices of endothelial damage and dysfunction than healthy controls and whether improved disease control was associated with improvement in these indices.MethodsTwenty-seven patients with active SLE (four or more American College of Rheumatology (ACR) criteria) and 22 age-matched controls were assessed. Endothelial microparticles (EMPs; CD31+/annexin V+/CD42b−) were quantified using flow cytometry. Brachial artery flow-mediated dilatation (FMD) was measured using automated edge-tracking software. Twenty-two patients had a second assessment at a median (IQR) of 20 (16, 22) weeks after initiating new immunosuppressive therapy.ResultsSLE patients had a median (IQR) baseline global British Isles Lupus Assessment Group Disease Activity Index (BILAG-2004) score of 14 (12, 22). CD31+/annexin V+/CD42b− EMPs were higher (157 548/ml (59 906, 272 643) vs 41 025(30 179, 98 082); p=0.003) and endothelial-dependent FMD was lower (1.63% (−1.22, 5.32) vs 5.40% (3.02, 8.57); p=0.05) in SLE patients than controls. CD31+/annexin V+/CD42b− EMPs correlated inversely with FMD (%) (r2 −0.40; p=0.006). At follow-up, the median (IQR) change in global BILAG-2004 score was −11 (−18, −3). CD31+/annexin V+/CD42b− EMP levels were reduced (166 982/ml (59 906, 278 775 vs 55 655(29 475, 188 659; p=0.02) and FMD had improved (0.33% (−2.31, 4.1) vs 3.19% (0.98, 5.09); p=0.1) at the second visit.ConclusionsActive SLE is associated with evidence of increased endothelial damage and endothelial dysfunction, which improved with suppression of inflammation. Better control of active inflammatory disease may contribute to improved cardiovascular risk in patients with SLE.

Isolation and Characterization of Microvesicles from Peripheral Blood

“…Also in patients with severe cerebral malaria an increase in total MVs in blood can be observed and counts of platelet-derived MVs correlate with coma depth and thrombocytopenia 12 . Other studies report elevated numbers of endothelium-derived vesicles in patients with systemic lupus erythematosus or heart failure and in the case of the latter, this correlates with a higher probability of cardiovascular events 13,14 .…”

The Association of Baseline and Longitudinal Change in Endothelial Microparticle Count with Mortality in Chronic Kidney Disease

“…Elevated numbers of these particles have been reported in association with a number of diseases such as an increased risk of acute coronary syndrome and cardiovascular death [16] , hypertension [17] , pre-eclampsia [18] and metabolic syndrome [19] . EMPs also have prognostic potential having been shown to correlate with clinical response to therapy in systemic lupus erythematosus [20] , and predict adverse events in otherwise stable coronary artery disease [16] . In CKD, higher circulating levels of EMP have been found in haemodialysis patients compared to pre-dialysis CKD, peritoneal dialysis and healthy controls [21][22][23] .…”

Correlation between brachial artery flow-mediated dilation and endothelial microparticle levels for identifying endothelial dysfunction in children with Kawasaki disease

“…EMPs play important roles in inflammation, coagulation, and regulation of vascular function. Significantly elevated levels of plasma EMPs were reported in cardiovascular diseases with endothelial dysfunction, such as acute coronary syndrome (13), pulmonary hypertension (14), diabetes (15), vasculitis (16), and others (17,18).…”

“…So far, the correlation between EMPs and FMD in KD patients has not been reported, although their relation has been studied in end-stage renal disease (23), diabetes (15), ischemic left ventricular function insufficiency (24), and obesity (16,25). During end-stage renal disease, circulating microparticles of endothelial origin are tightly associated with endothelial dysfunction and arterial dysfunction (23).…”