Abstract 2963: Circulating Endothelial Progenitor Cells in Patients with Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension
Background - Impaired endothelial homeostasis underlies the pathophysiology of pulmonary arterial hypertension (PAH). We hypothesized that patients with PAH are deficient in circulating endothelial progenitor cells (EPCs), potentially contributing to endothelial dysfunction and disease progression.
Methods and Results - We recruited 36 patients with Eisenmenger syndrome (12 with Down syndrome), 40 with idiopathic PAH (IPAH) and 17 healthy controls. Flow cytometry and in vitro assays were used to quantify EPCs and assess cell function. In addition, asymmetric dimethylarginine (ADMA, an endogenous NO antagonist), VEGF and MCP-1 - know to affect EPC mobilization - were measured.The number of circulating CD34+, CD34+/AC133+, and CD34+/AC133+/VEGFR2+ progenitor cells was low in Eisenmenger patients compared to healthy controls (Table 1⇓) and those with Down syndrome displayed even fewer EPCs (p<0.01). These effects correlated with NYHA functional class and six-minute walk distance (r=0.4, p=0.04). The capacity of cultured blood mononuclear cells to form colonies and incorporate into tube-like structures was also impaired in Eisenmenger patients (p<0.03 for each). In contrast, the number of circulating EPCs and colony forming units isolated from patients with IPAH was equal to or greater than controls. Furthermore, treatment with the phosphodiesterase inhibitor sildenafil was associated with a dose-dependent rise in EPC numbers (r=0.66, p=0.002), resulting in levels consistently above those found with other therapies.
Conclusions - Circulating EPC numbers and in vitro function differ in two well characterized forms of PAH. Patients with Eisenmenger syndrome display a reduction in EPCs that relates to functional capacity. In contrast, EPC numbers are normal in treatment naïve IPAH patients and elevated in sildenafil treated patients. Sildenafil treatment may represent a pharmacological means of chronically increasing circulating EPC numbers.