Atorvastatin Increases the Number of Endothelial Progenitor Cells After Cardiac Surgery: A Randomized Control Study

Abstract

Endothelial progenitor cells (EPCs) are a subtype of hematopoietic stem cells, which contribute to the repair of injured endothelium. Treatment with atorvastatin has been shown to increase EPC count in patients with coronary artery disease. Therefore, we investigated whether atorvastatin augments the number of EPCs after cardiopulmonary bypass (CPB) surgery. We conducted a randomized double-blind, placebo-controlled, 2-way crossover trial in 50 patients undergoing elective coronary surgery. Patients received either 3-week treatment with atorvastatin or placebo. EPCs were quantitated by flow cytometric phenotyping on blood samples. Levels of interleukin, IL-6 and IL-8; tumor necrosis factor alpha; SDF-1alpha; granulocyte colony-stimulating factor; and vascular endothelial growth factor were determined at recruitment, preoperatively, post-CPB, and 6, 12, and 24 hours postoperatively. The atorvastatin group showed a significantly higher amount of EPCs both pre- and postoperatively compared with the placebo, with a >4-fold increase compared with the baseline values. CPB induced an increase in all cytokines, but the levels of proinflammatory cytokines were significantly lower in the atorvastatin group (P < 0.05). Statin did not affect levels of SDF-1alpha, granulocyte colony-stimulating factor, and vascular endothelial growth factor. However, no correlation was found between plasma levels of any cytokine and number of EPCs, with the exception of SDF-1alpha. Pretreatment with atorvastatin significantly increases the amount of EPCs after CPB, by a mechanism independent of plasma levels of cytokines and cholesterol.

Current perspective of pathophysiological and interventional effects on endothelial progenitor cell biology: Focus on Pi3K/AKT/eNOS pathway

“…For instance, Vasa et al were one of the first to demonstrate that in CAD patients, EPC numbers and migratory capacity were found to be increased in the first weeks after atorvastatin treatment [10]. Recently, Spadaccio et al [127] reported the positive effects of a 3 week course of atorvastatin on circulating EPC numbers measured pre-and postoperatively in patients scheduled for cardiopulmonary bypass surgery. Surprisingly, Hristov et al [128] reported a reduction in EPC numbers in CAD patients under continuous (N3 months) treatment with statins.…”

Endothelial Progenitor Cell Number: A Convergence of Cardiovascular Risk Factors

“…LDL-C is inversely correlated with EPC number and function in human patients (Chen, Zhang et al 2004). Statin therapy has been shown to increase EPC numbers and function (Fadini, Albiero et al 2010;Jaumdally, Goon et al 2010) and to enhance EPC numbers in response to ischemic stimuli (Spadaccio, Pollari et al 2010;Hibbert, Ma et al 2011). The improvement of endothelial function associated with statin use is directly correlated with the increase in EPC numbers and measures of EPC function (Higashi, Matsuoka et al 2010).…”

Pleiotropic Effects of Long-Term Monotherapy with Rosuvastatin in Dogs with Moderate Heart Failure

“…Statins may induce angiogenesis by activating the protein kinase Akt-signaling pathway known to promote endothelial cell survival and nitric oxide production and by the VEGF-induced differentiation and mobilization from the bone marrow, and this effect has been confirmed in clinical studies [6]. Additionally, stem cell mobilization along with their known paracrine effect could be considered a key component of statin-induced CHF clinical improvement.…”