| Objective: AMP579 is a novel adenosine agonist with a long half-life period. It was relevantly reported that adenosine affects on patients with coronary heart disease proinflammatory cytokines, such as Tumor Necrosis Factor (TNF-α), interleukin-6 (IL-6) and interleukin-18 (IL-18),but it has not been reported that AMP579 affects on CD40L. Recently, studies have shown that CD40 ligand (CD40L) plays an important role in atherosclerosis (AS). The aim in our study is to observe the effects of AMP579 on expression of sCD40L in patients'serum with Acute Coronary Syndrome (ACS), and compared with the effects of adenosine in the same condition. This study will benefit to explore different role and mechanisms of different concentrations'AMP579 and adenosine on expression of sCD40L in patients'serum with ACS, and it will provide a theoretical basis for the treatment of coronary heart disease, and determine appropriate dose for clinical treatment. At the same time, sCD40L is compared with other effective indicators of atherosclerotic to evaluate sCD40L's role in ACS.Methods: The patients(15 patients with acute myocardial infarction diagnosed by clinical symptoms, changes of electrocardiogram and myocardial biochemical markers, 15 patients with unstable angina pectoris)and 15 normal individuals were drew blood. At the same time, different concentrations of adenosine and AMP579 intervened in blood plasma. At last, the expression of sCD40L in patients'serum was measured by ELISA. Meanwhile, sCD40L and the traditional coronary heart disease risk factors were related analyzed.Results: Expression of sCD40L in serum in patients with ACS was markedly higher than those in normal cases (p<0.05), and expression of sCD40L in patients with acute myocardial infarction (AMI) and unstable angina (UA) were significantly different (p<0.05). For UA patients, there is statistical difference between using AMP579 groups and using adenosine groups (F=49.610, p<0.01). For AMI patients, there is statistical difference between using AMP579 groups and using adenosine groups (F=171.362, p<0.001). For normal individuals, there is not statistical difference between using AMP579 groups and using adenosine groups (F=0.584, p>0.05). The half-logarithm line graphs show that the expression of sCD40L reduced with the increasing concentrations of adenosine and AMP579 in UA and AMI groups. In using AMP579 groups, the decreasing trend of expression level of sCD40L was more obvious. Expression of sCD40L in patients serum with AMI were total significantly different (F=501.059, p<0.001) with the different concentration of AMP579 (0μmol/L, 110μmol/L, 330μmol/L, 1.1×103μmol/L, 3.3×103μmol/L). The comparison of every two concentrations has statistical difference in using different concentrations of AMP579 for AMI patients. Expression of sCD40L in patients serum with UA were total significantly different (F=919.114, p<0.001) with the different concentration of AMP579 (0μmol/L, 110μmol/L, 330μmol/L, 1.1×103μmol/L, 3.3×103μmol/L). Except 3.3×103μmol/L and 1.1×103μmol/L, the comparison of every two concentrations has statistical difference in using different concentrations of AMP579 for UA patients. Expression of sCD40L in patients serum with ACS were total significantly different (p<0.001) with the different concentration of adenosine (0μmol/L, 330μmol/L, 1.1×103μmol/L, 3.3×103μmol/L, 11×103μmol/L). The comparison of every two concentrations has statistical difference in using different concentrations of adenosine for ACS patients. In patients with ACS, the expression level of sCD40L and CRP, APOB, TG, LDL-C and LP (a) was positive correlated, and the expression level of sCD40L, APOA and HDL-C was negative correlated. In patients with AMI, the expression level of sCD40L, CK-MB and aTnI was positive correlated.Conclusions: Expression of sCD40L in the ACS patients was markedly higher than those in normal cases. Expression of sCD40L in patients with AMI was higher than in those with UA. It suggested that sCD40L should involve in the occurrence of ACS. For UA patients, there is statistical difference between using AMP579 groups and using adenosine groups (F=49.610, p<0.01). For AMI patients, there is statistical difference between using AMP579 groups and using adenosine groups (F=171.362, p<0.001). By the data in the graph 1 and the fact that the lowest effective concentration of AMP579 is lower than adenosine, it was showed that AMP579 was stronger effective than adenosine. AMP579 is favourable to reduction of drug dosage in clinical application. Owing to the inhibitory action of sCD40L expression enhance with the increasing concentrations of adenosine, it showed that adenosine enhance the role of inhibiting platelet activation. Owing to the inhibitory action of sCD40L expression enhance with the increasing concentrations of AMP579 for AMI patients, it showed that AMP579 enhance the role of inhibiting platelet activation. By related analyzing sCD40L and blood-fat index, it suggested that decreasing CRP, APOB, TG, LDL-C, LP (a), CK-MB, aTnI and increasing APOA, HDL-C possibly decrease the expression level of sCD40L in patients with ACS. |
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