The Variation And Correlation Research Of The Soluble Tumor Necrosis Factor Related Apoptosis Inducing Ligand (sTRAIL) And Interleukin-10 In Acute Phase Of Acute Myocardial Infarction

The Variation and Correlation Research of the Soluble Tumor Necrosis Factor Related Apoptosis Inducing Ligand (sTRAIL) and Interleukin-10 in Acute Phase of Acute Myocardial Infarction.BackgoundIn resent years, there have been great progresses in research for the acute myocardial infarct. The present research discovered that apoptosis play the key role in the phenotye transition of the plaque from stable to vulnerable one. At present, it has been confirmed that apoptosis exist in acute myocardial infarction (AMI), and it is the important decisive factor in the acute phase of AMI, especially within 6 hours. It attracts our attention to study the relationship of AMI and apoptosis. Apoptosis result from oxygen deficiency, oxidize load, machine load, various kinds of cytokines, neuro-endocrine factors. The signals of apoptosis are transimitted by various pathways, involved to the expression tranfoems of apoptosis associated gene.According to initiation factors and pathways, apoptosis have been divided into two ways: receptor-depended and no receptor-depended, these ways exist in cross road each other. In the receptor-depended pathway, there is death receptor-mediated apoptosis pathway. Some reports pointed out that the death receptor-mediated apoptosis is the main mechanism by ischemic and oxygen deficiency. In the death receptor pathway, the most well-known are pathways of Fas/FasL and TNFRⅠ/TNF-α. It has been confirmed that they act very important role as apoptosis afterAMI. TRAIL/TRAILRs mediats apoptosis signals by death receptor pathway.Tumor necrosis factor related apoptosis inducing ligand (TRAIL ) belongs toⅡtransmembrane protein, it has five receptors: two death receptors DR4,DR5, two decay receptors DcR1,DcR2 and soluble receptor OPG. TRAIL mediates apoptosis only if it combines with DR4 and DR5, while protects from apoptosis in combination with DcR1 and DcR2. TRAIL has membrane and soluable ways. Because mTRAIL and sTRAIL can combine with DR4 and DR5, both of them may mediate the apoptosis. The research discovered that DR5 acts more important role as the process of medicating apoptosis. In resent years, some literatures reported plaque-infiltrating CD4+T cells can express TRAIL and the level of it increased upon stimulation in patients with acute coronary syndrome (ACS). Expression of TRAIL protein on PBMCs is significantly higher in the acute phase of AMI, it means that the express of membrane TRAIL (mTRAIL) increases. Expression of DR4 and DR5 in human cardiomyocytes was confirmed immunohistochemically and expression of DR5 was dominant, TRAIL and its receptors may involve in the induction of cardiomyocyte apoptosis after AMI. But it is not known whether soluble TRAIL (sTRAIL) may involve to inducing cardiomyocyte apoptosis after AMI.At present, the roles of releasing and adjustion of inflammatory reaction and correlative cytokine in ACS become the hot issue. Researchers think highly of the roles of pro-inflammatory cytokine. But there are a few reseaches for the anti-inflammatory regulatorymechanism of initiation and development progress in ACS. Cytokines are the core modifier in inflammatory reaction. Interleukin-10 (IL-10) intervention may reduce the myocardial cells apoptosis after ischemic reperfusion injury. Now, the anti-apoptsis mechanisms of IL-10 are still partially known.ObjectiveTo study the pathogenesy of the myocardial damage after AMI, we studied whether the acute phase of AMI in patients displayed variation and dependablity of another TNF family member sTRAIL and anti-inflammatory cytokine IL-10, Futhermore to study whether TRAIL/TRAILRs pathway involved in the induction of cardiomyocyte apoptosis after AMI and anti-apoptsis mechanisms of IL-10.MethodsWe compared the surum concentration of sTRAIL and IL-10 from 40 patients in the acute phase of AMI (29 men and 11 women, mean age 60.1±12.3 years) with 20 control subjects (14 men and 6 women, mean age 58.5±9.2 years) by enzyme liked immunosorbent assay (ELISA). Statistic analyses were performed with the SPSS11.5. Value were considered statistically significant at p<0.05.ResultsThe serum level of sTRAIL were higher in AMI group than that the control group (707.77±66.33pg/ml vs 384.46±43.83pg/ml, p<0.001), but The serum level of IL-10 were lower in AMI group than that the control group (10.31±2.37pg/ml vs 34.60±4.17 pg/ml, p<0.001). In addition, There was a inverse correlation between the serumlevel of sTRAIL and IL-10 in AMI group (r=-0.667, p<0.001).Conclusion1. sTRAIL and its death receptors may involve in the pathogenesy of the myocardial damage in the acute phase of AMI by inducing myocardial cell apoptosis.2. The serum higher level of sTRAIL may result from descending the inhibitory action of IL-10 in the serum lower level to pro-inflammatory, such as IFN-γ.3. The exogenous IL-10 intervention may reduce the myocardial cells apoptosis, so we deduced that sTRAIL/TRAILRs pathway may involve in the anti-apoptsis mechanisms of IL-10.