Study on Protective Effect of Atorvastatin-induced Increase of EPC-MVs on Myocardial Cells in STEMI Patients / 中国药房

ABSTRACT

OBJECTIVE： To observe the protective effect of atorvastatin-induced increase of EPC-MVs on myocardial cells in ST-segment elevation myocardial infarction （STEMI） patients， and to investigate its potential mechanism. METHODS： Totally 168 STEMI patients was collected from our hospital during Feb. 2015-Feb. 2018， and then divided into group A （88 cases） and group B （94 cases） according to the dose of atorvastatin. All patients received percutaneous coronary intervention， and then given Bivaleridine for injection， Clopidogrel bisulfate tablets and Atorvastatin calcium tablets. Group A was given Atorvastatin calcium tablets 20 mg， once a day. Group B was given Atorvastatin calcium tablets 20 mg， twice a day. A treatment course lasted for 30 d， and two groups were treated for 3 courses at least. The levels of blood lipid （TC， LDL-C， HDL-C） （before treatment and 30th， 60th， 90th day after treatment） and the number of EPCs positive cells （30th， 60th day after treatment） were observed in 2 groups. The expression of miRNA of EPC-MVs （60th day after treatment） was detected， and the expression difference of miRNA were validated. Target gene and KEGG pathway enrichment of miRNA with most significant expression difference were analyzed， and the effects of it on the proliferation of cardiac HCM-a cells were evaluated. The occurrence of ADR was recorded in 2 groups. RESULTS： Totally 8 patients withdrew from the study in group A， and 6 patients in group B. There was no statistical significance in the levels of TC， LDL-C and HDL-C or the number of EPCs positive cells in peripheral blood between 2 groups before treatment or 30th day after treatment （P＞0.05）. After treatment， the level of HDL-C in 2 group （60th and 90th day after treatment） and the number of EPCs positive cells in peripheral blood in group B （60th day after treatment） were increased significantly， and group B was significantly higher or more than group A at the same time point （P＜0.05）. Microarray analysis showed that compared with group A， 16 miRNAs expressed more than 1.5 times differentially in EPC-MVs of group B， 7 of which were up-regulated and 9 down-regulated. Top five differentially expressed genes were hsa-miR-126 （up-regulated）， hsa-miR-1275 （up-regulated）， hsa-miR-7704 （down-regulated）， hsa-miR-105-5p （down-regulated）， and hsa-miR-3180 （down-regulated）. Fluorescence quantitative polymerase chain reaction results showed that compared with group A， relative expression of hsa-miR-126 and hsa-miR-1275 in group B were increased significantly； and relative expression of hsa-miR-7704， hsa-miR-105-5p and hsa-miR-3108 were decreased significantly （P＜0.05）. The expression difference of hsa-miR-126 was the most significant， and its target genes included Ang-1， PDGF， p38 MAPK， Smad2/3， HIF-1， TGF-β， etc. The signaling pathways involved in regulation mainly included angiogenesis signaling pathway， chronic myelogenous leukemia related pathway， renal epithelial cell carcinoma related pathway and so on. CCK-8 test showed that the optical density （OD） of cells in hsa-miR-126 specific interfering substance group was decreased significantly， and the OD value of cells in simulated substance group was increased significantly， compared with blank group （P＜0.05）. There was no statistical significance in the incidence of ADR as diarrhea， nausea and vomiting， rash， etc. （P＞0.05）. CONCLUSIONS： Different doses of atorvastatin can regulate the level of HDL-C， and large dose of atorvastatin can increase the number of EPCs significantly， but dose not influence the safety of drug use. This effect may be associated with up-regulating the expression of hsa-miR-126 in EPC-MVs so as to promoting the proliferation of myocardial cells.