PURPOSE: Endothelial dysfunction plays a critical role in initiation and pathogenesis of pulmonary arterial hypertension (PAH) in sickle cell disease (SCD). Recent evidence suggests that bone marrow-derived circulating endothelial progenitor cells (EPCs) play an important role in post-natal blood vessel repair and neovascularization. We speculated that SCD patients with PAH are deficient in EPCs, potentially contributing to endothelial dysfunction and disease progression.
METHODS: We recruited 35 adult patients with SCD, out of which 14 patients were found to have PAH on 2D Echo (PASP ≥ 30mmHg). Flow cytometry was performed to quantify EPCs within 24 hours of sample collection. Eight different cell markers (CD34+, CD14-, CD106+, CD105+, CD31+, CD133+, KDR+, CD146+) were used to identify EPCs. Subgroups reacting to these markers were then further tested with 20 different marker combinations.
RESULTS: The number of circulating CD34+/CD14-/CD106+ progenitor cells i.e. Bone marrow cells (CD34+) expressing endothelial markers (CD106+) exclusive of Granulocytic/Monocytic origin (CD14-), was significantly low in SCD patients with PAH compared to non- PAH group (p<0.025). However CD133+/CD31+/CD146+ EPCs (Hematopoetic stem cells expressing endothelial markers) did not show a significant difference between two groups. Number of EPCs did not correlate with age, sex, body mass index (BMI), hemoglobin, WBC count, reticulocyte count, lactate dehydrogenase (LDH), creatinine clearance and use of hydroxyurea.
CONCLUSION: Our data indicates that (CD34+/CD14-/CD106+) EPCs were significantly decreased in SCD patients with PAH vs. without PAH. However EPCs with other markers such as CD133+/CD31+/CD146+ did not show a significant difference between the two populations, indicating that different subsets of EPCs might be involved in vascular repair. These findings suggest that relative deficiency of different EPCs subgroups in PAH patients may contribute to the pulmonary vascular pathology.
CLINICAL IMPLICATIONS: Identification and quantification of different types of EPCs in SCD/PAH patients indicates deficiency of certain subsets which might not only provide potential insight into the pathophysiological mechanisms but also might be useful for identifying suitable diagnostic and therapeutic targets in these patients.
DISCLOSURE: Fatima Anjum, No Financial Disclosure Information; No Product/Research Disclosure Information