Circulating endothelial progenitor cells in systemic sclerosis: relation to impaired angiogenesis and cardiovascular manifestations

Abstract

Objective: Given the essential role of endothelial progenitor cells (EPCs) in endothelial repair and neovascularization, it is likely that insufficient angiogenesis seen in systemic sclerosis (SSc) is related to EPC alterations. The present study was aimed to analyze in SSc the number of circulating EPCs and their contribution into cardiovascular involvement.

Methods: EPC (CD34+VEGF-R2+ and CD133+VEGF-R2+) circulating levels were evaluated in 40 SSc patients and 24 controls by FACS; their correlations with peripheral vascular manifestations, heart involvement, Framingham risk score, carotid artery disease, endothelial function and morphological signs of microangiopathy were studied.

Results: Early stage SSc and high disease activity were accompanied by a rise in circulating EPC levels in association with increased membrane expression of Fas (CD95) that correlated positively with severity of peripheral vascular manifestations. EPC reduction with disease progression was linked with endothelial dysfunction and capillary loss, and showed a strong relation to the development of severe internal organ (predominantly cardiac) involvement and pulmonary hypertension. There was a tendency to decreased EPC levels in SSc pts with low HDL values, but no significant correlations were found between EPCs and Framingham risk factor score, carotid artery IMT and traditional cardiovascular risk factors.

Conclusions: In early stage SSc mobilization of EPCs in response to tissue ischemia was preserved, but dropped with disease progression. EPC reduction may contribute to endothelial dysfunction and impaired angiogenesis, leading to the development of severe vascular life-threatening complications of SSc. Traditional cardiovascular risk factors and subclinical atherosclerosis did not influence EPC levels in SSc patients.