A Correlation Study Between Aspirin Resistance And Platelet MiRNA In Acute Cerebral Infarction Patients

BACKGROUDCerebral infarction, a kind of cerebral vascular disease with the highest incidence, the main cause of disability in adults, is the third leading cause of human death following malignant tumor and cardiovascular disease. Its incidence is increasing year by year, with high mortality rate and poor prognosis, giving a heavy burden to society and family. With many causes and complex pathogenesis, the interaction of genetic and environmental factors plays a vital role in the pathogenesis of cerebral infarction. Platelet activation, adhesion and aggregation is the important pathological process of acute cerebral thrombosis, therefore the anti platelet aggregation drugs such as aspirin is widely used in clinical application because of its positive role in treatment of the cerebral thrombosis. But aspirin resistance (AR) has limited its clinical effect, whose mechanism, however, is not clear at present. Platelet plays an important role in the occurrence of acute cerebral infarction, and some studies have found that the small RNA and platelet activity is closely related. We have learned the existence of a huge number of miRNAs in platelets, and miRNAs interfe ring with target protein expression by affecting mRNA, thus miRNAs play an important role in the body’s normal physiological and pathological process.But there are not related studies of the correlation of miRNA and aspirin resistance in patients acute cerebral infarction. OBJECTIVETo study the expression of platelet miR-126and miR-200b,miR-223,miR-495with their target proteins in Chinese Han population of Shandong area, and to investigate the correlation between platelet miRNA and aspirin resistance in patients with acute cerebral infarction, with finding out the mechanism of aspirin resistance from the point of view of genetics.METHODSTaking a case-control study,51patients with acute cerebral thrombosis patients were regarded as case group,60healthy people without cerebral infarction and myocardial infarction as control group. For participant, the general index of age, gender, object height, weight, blood pressure, body mass index were recorded and calculated, and risk factors of cerebral vascular disease such as history of hypertension, hyperlipidemia, coronary heart disease history and the history of diabetes, smoking history were recorded. Blood cell analysis, fasting blood glucose, fasting blood (FBG), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) were measured after blood collection in the early morning by using anticoagulation blood collection tube of1:9sodium citrate. The source of miR126was measured by flow cytometry, the platelet aggregation test was used to distinguish between aspirin and non aspirin resistance (NAR),.The levels of microRNAs were obtained by RT-PCR assay,and the expression of relative protein was gained by western bolt.RESULTS1. Diabetes, coronary heart disease, hypertension and smoking, alcohol drinking rate in case group than that of healthy control. Systolic blood pressure, fasting blood glucose, and platelet volume distribution width level were higher than that of the healthy control, and the high density lipoprotein level was lower than healthy control, and there are significant differences between the two groups through statistical analysis (P<0.05).2. There were8cases of AR in51cases of case group, and the incidence rate was16%.16AR cases were found in60cases of control group, and the incidence rate was27%. The difference was not statistically significant (χ2=0.16, P>0.05)3. The levels of miR126in case group were lower than in healthy control (with AS), and the difference was statistically significant (P<0.05).4. Of all the research objects, there was no statistical significance between AR and NAR in platelet miR-126levels (P>0.05).5. The expression of miR-126in case group between AR and NAR was not significant (P>0.05).6. Platelet miR-126levels in AR were significantly higher than NAR in control group (P<0.05), and by Logistic regression analysis, the platelet miR126is an independent risk factor for healthy human AR (OR=0.65,95%CI=1.22-30.05, P=0.03).7. The levels of platelet miR-200b and miR-495were significantly increased in case group compared with control group (p<0.05).8. In case group, miR-200b and miR-495of NAR were also profoundly upregulated by comparison with AR(p<0.05).9. In healthy controls, the levels of miR223were significantly downregulated in NAR(p<0.05).10. The expression of PRKAR2B and KLHL5was negative correlation with their relative microRNAs(miR-200b,miR-495).In case group and NAR of case group,PRKAR2B and KLHL5significantly reduced compared with relative groups(p <0.05).11.The expression of VASP was not consistent with PRKAR2B as we preconceived(p>0.05). 12. COX-1did not also show remarkable difference between NAR and AR(p>0.05).CONCLUSIONThe levels of platelet miR-126miR-223in the healthy controls and platelet miR-200b and miR-495of acute cerebral infarction patients are associated with the occurrence of aspirin resistance, and lower levels of platelet miR-126and high levels of miR-200b and miR-495indicate the occurrence of acute cerebral infarction to some extent.