Comparison of Endothelial Progenitor Cells in Parkinson's Disease Patients Treated with Levodopa and Levodopa/COMT Inhibitor

Background: Levodopa treatment in Parkinson's disease (PD) increases in serum homocysteine levels due to its metabolism via catechol O-methyltransferase. Endothelial progenitor cells (EPCs) have the capacity to differentiate into mature endothelial cells and are markers for endothelial functions and cardiovascular risks. Along with traditional vascular risk factors, hyperhomocysteinemia is known to decrease the level of EPCs. In the present study, we hypothesized that that levodopa-induced hyperhomocysteinemia leads to a change in EPC levels. Methodology/Principal Findings: We prospectively enrolled PD patients who had been prescribed either levodopa/carbidopa (PD-L group, n=28) or levodopa/carbidopa/COMT inhibitor (PD-LC group, n=25) for more than 1 year. The number of circulating EPCs was measured by flow cytometry using dual staining of anti-CD34 and anti-KDR antibodies. The EPCs were divided into tertiles based on their distributions and a logistic regression analysis was used to estimate independent predictors of the highest tertile of EPCs. The number of endothelial progenitor cells was significantly decreased in PD-L patients (118+/-99/mL) compared with either PD-LC patients (269+/-258/mL, p=0.007) or controls (206+/-204/mL, p=0.012). The level of homocysteine was significantly increased in PD-L patients (14.9+/-5.3 mu mol/L) compared with either PD-LC patients (11.9+/-3.0 mmol/L, p=0.028) or controls (11.1+/-2.5 mmol/L, p=0.012). The level of homocysteine was negatively correlated with endothelial progenitor cell levels (r=-0.252, p=0.028) and was an independent predictor of the highest tertile of endothelial progenitor cell levels (OR; 0.749 [95% CI: 0.584-0.961]). Conclusions/Significance: These data indicate that a higher consumption of EPC for restoration of endothelial damage may be associated with chronic levodopa treatment in PD patients.