Study On The Association Of Platelet Membrane P2X₁Receptor Mediated Platelet Activation With Acute Coronary Syndrome

Objective:Recently, incidence of acute coronary syndrome (ACS) have been on the rise. ATP and its platelet membrane P2X1receptor play an important role in platelet activation and are a potential antithrombotic therapy target. The objectives of this study are:firstly, to clarify the expression of P2X1receptor mRNA in ACS patients; secondly, to study the changes of the levels of Ca2+, P-selectin and glycoprotein IIb/IIIa (GPIIb/IIIa) after activating P2X1signal transduction pathway during platelet activation in ACS; thirdly, to study the effects of aspirin and clopidogrel on the changes of Ca2+, P-selectin and GPIIb/IIIa after P2X1receptor activation.Method:A total of70patients with ACS and20people were recruited in this study.Reverse transcription PCR and real-time quantitative PCR were used to quantify the mRNA levels of P2X1receptor and GPIIb/IIIa receptor in platelet.The Ca2+concentrations in platelets were measured with a fluometer using Fluo-3AM as indicator. The platelets were isolated and activated by a,B-me ATP (3μM) before and after treatment with aspirin and clopidorel. The levels of P-selectin and GPIIb/IIIa were measured by enzyme linked immunosorbent assay (ELISA) after activation by low concentrations of collagen (1μg/ml).Result:The expression of P2X1receptor and GPIIb/IIIa receptor was detected in control group and ACS group, and the expression of the two receptors in ACS group was significantly higher than those in control group (P<0.05).The basal levels of Ca+were higher in ACS group than those in controls (P<0.05). After medical intervention, Ca2+levels were decreased in ACS group (P<0.05) but the magnitude is less than that in control group (P<0.05). The basal levels of Ca2+was higher in AMI group than those in UA group (P<0.05), and after medicine treatment, it showed a decrease in ACS group (P<0.05) but the magnitude is less than that in control group (P<0.05). The basal levels of P-selectin and GIIb/IIIa were higher in ACS group than those in controls (P<0.05) and after drug intervention, it showed a decrease in ACS group (P<0.05) but the magnitude was less than that in controls (P<0.05). No significant association between AMI group and UA group in the levels of P-selectin and GIIb/IIIa was observed. Conclusion:The expression of P2X1receptor mRNA was higher in ACS group. The P2X1signaling pathway was activated during ACS leading to high levels of Ca2+, P-selectin and GPIIb/IIIa; aspirin and clopidorel treatment could inhibit the signaling transduction of P2X1receptor. Hence, high levels of Ca2+, P-selectin and GPIIb/IIIa induced by platelet surface receptor P2X1activation played important role of occurrence and progress of ACS.