Endocan and Circulating Progenitor Cells in Women with Systemic Sclerosis: Association with Inflammation and Pulmonary Hypertension

Abstract

Background: Systemic sclerosis (SSc) is characterized by early vasculopathy and fibrosis in the skin, lungs, and other tissues. Vascular manifestations of SSc include Raynaud's phenomenon, digital ulcers, and pulmonary artery hypertension (PAH). PAH is the second most common cause of mortality in SSc. Circulating CD34+ cells associated with cardiovascular health status in several conditions, including chronic immune-inflammatory disease. CD34+ cell numbers have been found inconstantly reduced in SSc. Endocan, a proteoglycan expressed by endothelial cells, was recently suggested as a marker of vascular stress. We tested the relationships among CD34+ cells, endocan, inflammatory markers, vitamin D levels, and clinical parameters in SSc patients with PAH.

Methods: Standard echocardiography was performed. Vitamin D levels, CD34+ cells, inflammatory markers, endocan plasma levels were determined in 36 female SSc patients (24 diffuse/12 limited) and 36 matched controls (HC).

Results: We found no difference in CD34+ and vitamin D levels in SSc as compared to controls; ESR, CRP, fibrinogen, endocan, sPAP were higher in SSc with respect to controls. We found a correlation between endocan and: CD34+ cells (r: -0.540, p = 0.002), pulmonary arterial pressure (sPAP) (r: 0.565, p < 0.001), tricuspid annular plane excursion (TAPSE) (r: -0.311, p < 0.01), and E/A ratio (r: -0.487, p < 0.001), but not with ejection fraction (r: -0.057, p = 0.785) in SSc. CD34+ cells correlate with fibrinogen (r: -0.619, p < 0.001), sPAP (r: -0.404, p = 0.011), E/A (r: 0.470, p < 0.005 in SSc.

Conclusion: CD34+ cell number was significantly correlated with endocan levels and with sPAP in SSc; endocan and CD34+ progenitor cells might be suggested as a potential marker of disease status.

Keywords: circulating progenitor cells; endocan; pulmonary hypertension; systemic sclerosis.

Figure 1

Flow diagram for inclusion/exclusion path. 73 records found regarding female patients with diagnosis confirmed of SSc; 3 patients did not have entries relating to the period considered; 3 had started O2 therapy; 9 had COPD, or were assigned to WHO FC > 3, or were smokers, or walked a distance < 350 m; 4 subjects were excluded due to relevant comorbidities (3 for arterial hypertension, 1 for type 2 diabetes mellitus); 9 were not eligible due to missing needed echocardiography parameters; 8 were excluded because we did not find the blood sample stored in our bio-bank; finally, 1 patient was excluded after the primary selection because of the unreliability of echocardiography parameters.

Figure 2

Spearman’s correlation between CD34+ and endocan (a); sPAP and endocan (b); sPAP and CD34+ (c); CD34+ and fibrinogen (d); CD34+ and Vitamin D (e); sPAP and fibrinogen (f).