Correlations between angiogenic factors and capillaroscopic patterns in systemic sclerosis

Abstract

IntroductionWe sought to assess whether nailfold videocapillaroscopy (NVC) patterns are associated with levels of angiogenic factors in systemic sclerosis (SSc).MethodsCirculating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) were measured in the peripheral blood of 60 consecutive SSc patients. Serum levels of eight endothelial markers were measured first in these 60 patients, and then in an independent replication cohort of 43 SSc patients in case of association with NVC patterns. NVC patterns were determined by four independent investigators blinded to vascular markers.ResultsPatients with the late-NVC pattern exhibited lower EPC levels (P < 0.0001) and higher VEGF levels (P = 0.03). Higher VEGF levels were confirmed to be associated with the late-NVC pattern in the replication cohort (P = 0.01). By multivariate analysis focused on biomarkers, lower EPC (P = 0.03) and higher VEGF levels (P = 0.001) were independently associated with the late-NVC pattern. In an alternate multivariate model including these two factors and SSc-related disease characteristics, lower EPC counts (P = 0.005), higher VEGF levels (P = 0.01), a history of digital ulcers (P = 0.04), and a modified Rodnan skin score > 14 (P < 0.0001) were independently associated with the late-NVC pattern.ConclusionOur data revealed decreased EPC counts and increased VEGF levels in patients with the late-NVC pattern. Further studies are now needed to determine the role of VEGF and EPCs in endothelial injury and repair in SSc.

Decreased numbers of endothelial progenitor cells in patients in the early stages of systemic sclerosis

“…In SSc patients, the typical SD pattern, which is characterized by the presence of enlarged capillaries, capillary loss and distortion of the capillary array (De Angelis et al, 2009), might be related to impaired vasculogenesis. Interestingly, as observed recently in another study (Avouac et al, 2013), we observed decreased levels of EPCs in patients who presented with the late SD pattern on NFC. Indeed, the late SD pattern is characterized by severe capillary loss and disorganization of the capillary array (Cutolo et al, 2004) and might be associated with a decrease in EPC count.…”

Skin Telangiectasia and the Identification of a Subset of Systemic Sclerosis Patients With Severe Vascular Disease

“…Taken together, these observations support the idea that an increase in the number and size of CT may be an aberrant attempt at vascular recovery in response to insufficient blood flow, to increase blood perfusion and oxygen supply to hypoxic tissues. Increased vascular endothelial growth factor (VEGF) levels have been reported in patients with the late NVC pattern and particularly with neoangiogenesis (13). Indeed, a chronic and uncontrolled overexpression of VEGF has been implicated in the altered and anarchic vessel morphology that characterizes neoangiogenesis and thus, VEGF overexpression may also drive the formation of profuse and pseudotumoral CT.…”

“…In that case, patients with absent or minor to moderate CT were merged together and further compared with patients with profuse CT. Patients with early and active NVC pattern were merged together and further compared with patients with the late NVC pattern, as previously reported (13). Analysis of variance was used to test the difference between the means of several subgroups of a variable.…”

Therapeutic effect of methotrexate encapsulated in cationic liposomes (EndoMTX) in comparison to free methotrexate in an antigen-induced arthritis study in vivo

“…For example, vascular endothelial growth factor (VEGF) is increased in angiogenesis in RA by high-mobility group box protein 1 (HMGB1) (52), also seen in other disease developments such as in systemic sclerosis (53), where microvascular damage and dysfunction represent the earliest morphological and functional markers (54).…”