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.

Diet in Scleroderma: Is There a Need for Intervention?

“…The latter finding could partially explain the absence of a notable relationship between MUST scores and caloric or macronutrient consumption. Moreover, this points to important non-dietary factors being involved in the appearance of weight loss in our study group [2][3][4]. In this respect, we obtained statistically significant connections with mRSS and other disease-related changes.…”

“…Systemic sclerosis (SSc) is a rare chronic autoimmune disease mainly characterized by microvasculopathy, together with a widespread fibrosis of the skin and viscera [1]. SSc patients demonstrate an abundance of risk factors for nutritional decline, including the presence of chronic inflammation and the progressive nature of disease-related multisystem involvement [2][3][4].…”

Role of Vitamin D in Systemic Sclerosis: A Systematic Literature Review

“…It has been suggested that typical skin manifestations such as fibrosis and, to a lesser extent, calcinosis cutis may reduce vitamin D synthesis and influence the other clinical manifestations in scleroderma patients, with differences between diffuse (dcSSc) and limited cutaneous SSc (lcSSc). A closer look at the potential association between levels of vitamin D and the clinical phenotype of SSc showed no significant difference in vitamin D or its active metabolite 25(OH)D levels, irrespective of the disease subtype, in the majority of studies [ 10 , 16 , 22 – 24 , 41 , 45 ]. However, An et al demonstrated lower serum vitamin D in SSc compared with healthy controls and in dcSSc compared to lcSSc.…”

“…Hypovitaminosis D is a general finding in scleroderma [ 3 – 5 , 9 , 10 , 13 , 15 , 16 , 21 , 25 , 27 , 34 , 35 ], and based on its pleiotropic effects, including its immunomodulatory, cardioprotective, and antifibrotic properties, low vitamin D status could influence the pathogenetic pathways activated in SSc [ 30 ]. Nevertheless, the association between abnormal vitamin D status and SSc onset, or any of its clinical manifestations, is still under debate [ 30 ].…”

“…Much attention has recently been given to CD34+ CD45- endothelial progenitor cells as a marker of early vascular activation and endothelial lesions in SSc, which could potentially be useful for disease activity estimation [ 66 ]. In a recent study, Lo Gullo et al found an inverse correlation between vitamin D levels and CD34+ cell numbers in SSc patients [ 10 ].…”