A Preliminary Study On The Relationship Between The Levels Of Plasma TRAIL, DR5 And OPG And Acute Coronary Syndrome

OBJECTIVES: This study is designed to investigate the difference levels of tumor necrosis factor related apoptosis inducing ligand (TRAIL), death recrptor 5(DR5), osteprotegerin (OPG) in both peripheral plasma and ascending aorta in different subtype of coronary artery disease (CAD), and to explore the relationship between them and plasma high sensitivity C-reactive protein (hsCRP) levels, number of coronary artery involved, and ACS, respectively.BACKGROUND: ACS is a series of emergenecies including unstable angina pectoris (UAP), acute myocardial infarction (AMI) and sudden cardiac death. It usually attacks suddenly and has a high risk for death.The pathogenesis of ACS is the rupture of vulnerable plaques and the occlusion of coronary artery secondary to platelet aggregation and thrombsis. Inflammation plays a critical role in the stability of atherosclerosis (As) plaque. Both TRAIL and its receptors could be expressed in vascular endothelial cells, vascular smooth muscle cells and kinds of inflammatory cells involved in As, execute a dual role in facilitating and antagonizing cell apoptosis,and contribute to the genesis and development of As.METHODS: The 62 patients with CAD were divided into two groups: 40 in the ACS group, including 22 patients with UAP and 18 with AMI, and 21 in the stable angina pectoris (SAP) group. Twenty-two subjects who underwent coronary angiography but show no evidence of CAD served as normal coronary artery (NCA) group. Peripheral plasma TRAIL, DR5, OPG and hsCRP levels from these people were assayed by ELISA. Ascending aortas from 22 subjects were obtained, of which 8 were from the ACS group, 7 from the SAP group and 7 from the NCA group. Semi-quantitative reverse-transcription polymerase chain reaction was used for the detection of TRAIL, DR5 and OPG mRNA.RESULTS:1.There was no statistical difference in the distribution of age, gender, body mass index (BMI), smoking, systolic blood pressure (SBP), diastolic blood pressure(DBP), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) among the three groups. The histories of MI, cerebrovascular accident (CVA), percutaneous trans-luminal coronary angioplasty (PTCA), d iabetes mellitus (DM) and hypertension and number of coronary ateries affected in patients with ACS and SAP were not significantly different. Compared with NCA group, the levels of high-density lipoprotein cholesterol (HDL-C) and lipoprotein cholesterol(α) [Lp(α)] h ad a markedly increase in the ACS and SAP group. The patients with ACS had a higher fasting glucose levels than those with SAP and NCA. Though white cell count (WBC) rose gradually from NCA group to ACS group, only those in the ACS group had a statistical increase when compared with those in the NCA group. There were no statistically significant difference in the use of nitrates, aspirin, clopigerl, statins, beta-blockers, calcium-channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) between the ACS and SAP group. Multiple linear regression analyses revealed that medications had no influence on the plasma levels of TRAIL, DR5 and OPG.2.Compared with the NCA and SAP groups, plasma TRAIL, OPG, hsCRP levels were significantly increased in the ACS group (P<0.001). Patients with ACS had a markedly greater plasma DR5 level than those with NCA (P<0.05).3.Plasma TRAIL, DR5, OPG and hsCRP levels in patients with 3-vessel involved ACS were significantly higher than those in patients with 1-vessel(P<0.001, P<0.05, P<0.05 and P<0.05, respectively). The patients with 3-vessel involved ACS had markedly raised plasma TRAIL level when compared with the patients with 2-vessel (P<0.05). In the 2-vessel group, only plasma DR5 and hsCRP levels had a statistically significant greater than those in the 1-vessel group (P<0.05). There was no difference in plasma TRAIL, DR5 and OPG levels of ACS subgroup, but patients with AMI had a higher plasma hsCRP level than those with UAP(P<0.05).4.Plasma hsCRP level was found to positively correlated with TRAIL, DR5 and OPG, respectively. There were also positive correlation among TRAIL, DR5 and OPG.5.Logistic stepwise regression analyses revealed that odds ratio (OR) of TRAIL, OPG and WBC is 1.012 (P=0.002), 1.013 (P=0.007) and 2.533 (P=0.034), respectively.6.Ascending aorta from the ACS group exhibited markedly higher TRAIL and OPG expression as compared with those from the SAP group(P<0.05). TRAIL and OPG mRNA expression were significantly higher in ascending aorta from the ACS group than those from the NCA group. Though DR5 mRNA expression in ascending aorta increased gradually from the NCA, SAP to ACS group, the difference was not statistically significant.CONCLUTIONS: 1.Plasma TRAIL, DR5 and OPG levels, which raised with increased vessels involved in ACS group, were markedly higher in patients with ACS.2.Ascending aortas from patients with ACS had a significantly high TRAIL and OPG mRNA expression.3.All of TRAIL, DR5 and OPG may contribute to the inflammatory process of As.4.Both TRAIL and OPG could be independent risk factors for ACS.