Abstract 20953: Effects of Rosuvastatin and Allopurinol on Endothelial Progenitor Cells in Patients With Chronic Heart Failure: The Role of Inflammation and Oxidative Stress
Background: Endothelial progenitor cells (EPCs) play a significant role in the reendothelialization and vascular repair, while reduced number of EPCs identifies patients at increased risk for major adverse cardiac events. We investigated the effects of rosuvastatin and allopurinol on the number of EPCs in patients with heart failure and the relations of pro-inflammatory cytokines and oxidative stress to the levels of these cells.
Methods: Sixty clinically stable patients with systolic heart failure were randomized double-blind to receive rosuvastatin 10 mg/d, allopurinol 300 mg/d or placebo and followed up for 1 month. The number of EPCs (CD34+/KDR+ and CD34+/AC133+/KDR+) in blood was evaluated by flow cytometry. Endothelial function was assessed by brachial artery flow-mediated dilation. Levels of myeloperoxidase (MPO) and total lipid peroxides in plasma, as well as vascular endothelial growth factor, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, interleukin-6, interleukin-1θ, and oxidized LDL in serum were determined by ELISA.
Results: CD34+/KDR+ and CD34+/AC133+/KDR+ cells were significantly increased in rosuvastatin-treated group (from 0.023 (0.017-0.038) and 0.001 (0.0008-0.0024) to 0.039 (0.023-0.052) cells/100 mononuclear cells (MNCs) and 0.0019 (0.0008-0.0033) cells/100 MNCs respectively, p=0.004 and p=0.008), whereas they remained unchanged in the other groups. The increase in levels of CD34+/KDR+ EPCs induced by rosuvastatin was significantly greater compared with that induced by allopurinol and placebo (difference between groups p<0.05). In the entire study group, a significant correlation was observed between the baseline levels of CD34+/KDR+ cells and MPO (r=0.351, p=0.005) and sCD40L (r=0.313, p=0.013). After controlling for potential confounders, only body mass index (θ=−0.39, p=0.049) and MPO levels (θ=0.49, p=0.047) were significant predictors of EPC numbers.
Conclusions: Short-term treatment with rosuvastatin, but not allopurinol, significantly increases the number of circulating EPCs in patients with heart failure. Furthermore, EPC levels are significantly associated with plasma levels of MPO suggesting a possible role of MPO in the mobilization of EPCs in such patients.
- © 2010 by American Heart Association, Inc.