Characterization of altered patterns of endothelial progenitor cells in sickle cell disease related pulmonary arterial hypertension

Fatima Anjum, Jason Lazar, Joe Zein, Ghassan Jamaleddine, Spiro Demetis, Raj Wadgaonkar, Fatima Anjum, Jason Lazar, Joe Zein, Ghassan Jamaleddine, Spiro Demetis, Raj Wadgaonkar

Abstract

Endothelial dysfunction plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH) in sickle cell disease (SCD). A variety of evidence suggests that circulating endothelial progenitor cells (EPCs) play an integral role in vascular repair. We hypothesized that SCD patients with PAH are deficient in EPCs, potentially contributing to endothelial dysfunction and disease progression. The number of circulating CD34+/CD14-/CD106+ EPCs was significantly lower in SCD patients with PAH than without PAH (P=0.025). CD34+/CD14-/CD106+ numbers significantly correlated with tricuspid regurgitation velocity (TRV, r=-0.44, P=0.033) 6-minute walk distance (6MWD, r= 0.72, P=0.001), mean pulmonary artery pressure (mPAP, r= -0.43, P=0.05), and pulmonary vascular resistance (PVR, r=-0.45, P=0.05). Other EPC subsets including CD31+/CD133+/CD146+ were similar between both groups. Numbers of EPCs did not correlate with age, sex, hemoglobin, WBC count, reticulocyte count, lactate dehydrogenase (LDH), iron/ferritin levels, and serum creatinine. These data indicate that subsets of EPC are lower in SCD patients with PAH than in those without PAH. Fewer EPCs in PAH patients may contribute to the pulmonary vascular pathology. Reduced number of EPCs in SCD patients with PAH might not only give potential insight into the pathophysiological mechanisms but also might be useful for identifying suitable therapeutic targets in these patients.

Keywords: associated pulmonary arterial hypertension; pathogenic mechanism; sickle cell disease; stem cell.

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
Flow cytometric analysis and characterization of cell surface markers on EPC from peripheral blood. Using several[8] distinctive cell markers (CD34, CD14, CD106, CD105, CD31, CD133, KDR, CD146) in 20 different combinations in both groups of patients flow cytometric analysis was performed as described in the “Methods” section. EPCs with CD14−/CD34+/CD106+ markers showed a significant difference between SCD patients with PAH versus without PAH (P=0.025), while EPCs with CD31+/CD34+/CD146+ markers and CECs did not show any significant difference between the two groups of patients. Statistical analysis was performed as described in the methods section.
Figure 2
Figure 2
Correlation of EPC’ with various PAH parameters. EPCs with CD34+/CD14−/CD106+markers (EPC Group-1) were found to be to be significantly correlated with TRV on Doppler echo (r=−0.44, P=0.033), 6MWD (r=0.72, P=0.001), mPAP (r=−0.43, P=0.05), and PVR (r=−0.45, P=0.05) on RHC. Multivariate regression analysis was applied to determine independent relations of all clinical variables with EPCs. A P value ≤0.05 was considered statistically significant.

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