EP3 Receptor On Platelets In Patients With Acute Non ST-segment Elevation Myocardial Infarction

Background and objective:Acute coronary syndrome is the most common acute critical disease in cardiovascular disease.Among hospitalized patients with ACS,acute non-ST-segment elevation myocardial infarction accounted for more than 70%.Previous studies on coronary heart disease have found that atherosclerotic plaque rupture can promote the production of prostaglandin E2(PGE2),thus activating prostaglandin E receptor(EP3)on platelets,promoting platelet aggregation and leading to thrombosis.Which can aggravate the progression of the disease.The current clinical application of antiplatelet drugs is limited by bleeding problems and drug resistance in some patients.EP3 receptor plays an important role in the regulation of blood vessels and modification of blood vessel wall in the process of human platelet aggregation and thrombosis.EP3 receptor inhibitors can not only effectively inhibit platelet aggregation,but also do not prolong bleeding time,which is a new target for anti-platelet aggregation therapy.However,to date,there are few studies on the changes of EP3 receptor levels in patients with acute non-ST-segment elevation myocardial infarction.Therefore,this study aims to investigate the expression of EP3 receptor in acute non-ST-segment elevation myocardial infarction,its relationship with platelet function,and its predictive value for acute non-ST-segment elevation myocardial infarction,and to compare the effects of different EP3 receptor expressions on platelet reactivity after antiplatelet therapy.To explore the effect of EP3 receptor expression on platelet function in patients with acute non-ST-segment elevation myocardial infarction and platelet reactivity after antiplatelet drug treatment,and to provide theoretical research basis for the treatment of acute non-ST-segment elevation myocardial infarction.Methods:1.105 patients diagnosed with acute non-ST-segment elevation myocardial infarction in the Department of Cardiology,People’s Hospital of Pudong New Area in Shanghai from September 2020 to March 2021 were selected as the study group(NSTEMI group),and 98 healthy subjects in the same age group were included as the control group.There were 64 males and 41 females in the study group,with an average age of(67.21±18.1)years,and 56 males and 42 females in the control group,with an average age of(61.88±20.1)years.2.Collect the data of all the enrolled personnel,The age(years),gender,weight(kg),height(cm),body mass index(kg/m2),smoking history,drinking history,coronary heart disease history,hypertension history,diabetes history,TC(total cholesterol),TG(triglyceride),low-density lipoprotein(LDL-C),serum creatinine,brain natriuretic peptide(BNP),cardiac troponin Ⅰ were collected(cTnⅠ),activated partial thromboplastin time(APTT),plasma prothrombin time(PT),plasma thrombin time(TT)levels,left ventricular ejection fraction(LVEF).3.Venous blood samples were used as the main research object.A total of 3ml fasting venous blood samples were collected from the two groups and Thromb elastograph(TEG)was performed within 2 hours after blood sampling.The reaction time(R),coagulation time(K),Angle Alpha(α)and maximum amplitude(MA)were obtained.The concentration of PGE2 in blood was detected by ELISA,and the expression of EP3 receptor in blood samples was detected by flow cytometry.4.The differences of thrombelastography parameters and EP3 receptor expression levels between the two groups were compared.Pearson linear correlation analysis was used to analyze the correlation between thrombelastography parameters and EP3 receptor expression levels.ROC analysis was used to analyze the auxiliary diagnostic value of thrombelastography parameters and EP3 receptor expression level for NSTEMI.5.The study group was divided into normal platelet response group and abnormal platelet response group according to the induction of adenosine diphosphate(ADP)after taking aspirin and clopidogrel:If the platelet aggregation rate induced by 2umol/L ADP was≥70%,or the platelet inhibition rate was<30%,the response to clopidogrel was low(anti-platelet ineffective),and the abnormal platelet response group was defined as the platelet aggregation rate≥70%,or the platelet inhibition rate<30%.Patients with normal platelet response were defined as normal platelet response group.The differences of EP3 receptors on platelets between the two groups were compared.Results:1.A total of patients with acute non-ST-segment elevation myocardial infarction were enrolled in this study,including 105 cases in the study group and 98 cases in the control group.The levels of TC,TG,BNP,cTnI and LDL-C in the study group were higher than those in the control group(P<0.05),while the levels of APTT,PT,TT and LVEL in the study group were lower than those in the control group(P<0.05).There was no significant difference in other general baseline information between the two groups.2.The Angle value,MAThrombin value and MAADP value of the study group were higher(P<0.05 or P<0.01),while the K value was lower(P<0.01).3.The concentration of PGE2 and the expression of EP3 receptor in the study group were significantly higher than those in the control group(P<0.05).4.Pearson correlation coefficient linear analysis results showed that EP3 receptor and MAThrombin,MAADP parameters showed a strong correlation(0.8<r<1,P<0.05),EP3 receptor and K value,MAFibrin showed a strong correlation(0.6<r<0.8),EP3 receptor and MAthrombin,MAADP parameters showed a strong correlation(0.8<R<1,P<0.05).However,there was no significant correlation between EP3 receptor and R value or Angle value(P>0.05).5.Angle value,MAThrombin,MAADP,K value,PEG2 concentration,EP3 receptor expression level and other statistically significant factors were used as covariates,and NSTEMI was used as dependent variable.logistic regression analysis showed that the independent risk factors for acute myocardial infarction were MAThrombin(P<0.001),MAADP(P<0.001)and EP3 receptor expression level(P<0.001).The ROC curve was used to analyze the diagnostic efficacy of MAThrombin,MAADP and EP3 receptor for acute non-ST-segment elevation myocardial infarction.According to the area under the curve,the area under the ROC curve of EP3 receptor was 0.867 in the prediction of acute non-ST-segment elevation myocardial infarction.The area under the curve of MAADP was 0.816,that is,the diagnostic efficacy of EP3 receptor was higher than that of MAADP,and the diagnostic efficacy of both EP3 receptor and MAThrombin was higher than that of MAADP(area under the curve=0.736).6.After taking aspirin and clopidogrel,the study group was divided into abnormal platelet response group(20cases)and normal platelet response group(85cases)according to ADP induction.The expression of EP3 receptor in the two groups was(37.24±2.38)and(35.03±4.02),respectively(P=0.027).According to EP3 receptor expression,patients were divided into EP3 receptor high expression group(19 cases)and EP3 low expression group(86 cases),and the ADP inhibition rates of the two groups were(25.24±2.21)and(55.18±3.35),respectively(P<0.01).MAADP(mm)were(54.12±5.35)and(41.65±4.52),respectively(P<0.01).Conclusion:1.The expression of EP3 receptor is significantly increased in patients with acute non-ST-segment elevation myocardial infarction,which is associated with abnormal platelet function and is a high risk factor for thrombosis.2.In patients with high EP3 receptor expression,antiplatelet therapy is not effective.EP3 receptor inhibitors will provide a new option for antiplatelet therapy.