Atorvastatin increases the number of endothelial progenitor cells after cardiac surgery: a randomized control study
Cristiano Spadaccio1, Francesco Pollari, Adele Casacalenda
1Department of Cardiovascular Sciences, University Campus Bio-Medico of Rome, Rome, Italy.
Insights
Atorvastatin significantly increases endothelial progenitor cells (EPCs) after cardiopulmonary bypass surgery. This effect occurs independently of changes in plasma cytokines or cholesterol levels.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Pharmacology
Background:
- Endothelial progenitor cells (EPCs) are crucial for repairing injured blood vessels.
- Atorvastatin, a statin medication, has been linked to increased EPC counts in coronary artery disease patients.
- Cardiopulmonary bypass (CPB) surgery can impact endothelial function and cell repair mechanisms.
Purpose of the Study:
- To investigate the effect of atorvastatin on EPC numbers following CPB surgery.
- To determine if atorvastatin influences cytokine levels in the context of CPB.
- To explore the relationship between EPCs, cytokines, and atorvastatin treatment.
Main Methods:
- A randomized, double-blind, placebo-controlled, 2-way crossover trial involving 50 patients undergoing elective coronary surgery.
- Patients received either atorvastatin or placebo for 3 weeks prior to surgery.
- EPCs were quantified using flow cytometry; various cytokines were measured at multiple time points.
Main Results:
- The atorvastatin group exhibited significantly higher pre- and postoperative EPC counts (>4-fold increase from baseline) compared to placebo.
- CPB increased cytokine levels, but atorvastatin treatment led to significantly lower proinflammatory cytokine levels.
- Atorvastatin did not alter levels of SDF-1alpha, G-CSF, or VEGF, and EPC counts correlated with SDF-1alpha only.
Conclusions:
- Pretreatment with atorvastatin significantly enhances EPC levels after CPB surgery.
- The mechanism by which atorvastatin increases EPCs appears independent of plasma cytokine and cholesterol levels.
- Atorvastatin may offer a therapeutic benefit in promoting endothelial repair post-cardiac surgery.
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.
