The Impact Of Different Doses Of Alto Atorvastatin On Myocardial Injury In Rat Endothelial Progenitor Cell Mobilization And Vascular Endothelial Function

Objective To investigate whether atorvastatin dose-dependently affects endothelial progenitor cells(EPCs)mobilization from peripheral blood and bone marrow culture invitro and endothelial function in rats with myocardial injury.Methods rats with myocardial injury, induced by isoprenaline,were randomized to treatment with vehicle (V) or atorvastatin(Ator, 5,10,20, 40,80mg/kg QD by gavage) for 4 weeks startingon first day after Myocardial injury. Putative precursorpopulations (CD34+/VEGFR-2+ haematopoietic stem cells) weremeasured by flow cytometric analysis. Total mononuclear cells(MNCs) were isolated from peripheral blood by Ficoll densitygradient centrifugation, and the cells were plated on gelatincoated culture dishes. Double-stained cells for both FITC BS-1lectin and acLDL-DiⅠwere counted as EPCs in at least 3 randomlyselected HPFs. Serum concentration of NO was measured 3 daysafter atorvastatin use.Results atorvastatin increased EPCs numbers both in bonemarrow and peripheral blood culture in vitro, maximum at40mg/kg(P＜0.05). EPCs numbers at the dose of 80mg/kg wereslightly reduced comparing with 40mg/kg, but there was no statistical difference; circulating EPCs (double positiveCD34+/VEGFR-2+) were significantly elevated after myocardialinjury (P＜0.05); EPCs mobilization was markedly furtheraugmented by atorvastatin treatment, maximum at 80mg/kg(4.18-fold increase, P＜0.05). There was no statisticaldifference between 40mg/kg vs 80mg/kg group; Atorvastatininduced a dose-dependent increase in serum concentration of NOgeneration, with maximal effect at dose of 80mg/kg.Conclusion atorvastatin dose-dependently improveendothelial progenitor cells(EPCs) mobilization, EPCs numbersin vitro culture and endothelial function.