The Correlation Between Plasma Interleukin-15 Level And Severity Of Coronary Artery Stenosis In Patients With Coronary Heart Disease

BackgroundCoronary heart disease(CHD) is characterized by atherosclerosis(AS) in the epicardial coronary arteries, stenosis of the lumen, rupture of the plaque, and acute thrombus formation, which unbalance the supply of blood and oxygen, finally leading to myocardial ischemia and hypoxia. Atherosclerosis as the core mechanism of CHD has complex pathogenesis including dyslipidemia, cytokines impropriate secretion, dysregulation of blood coagulation factors, hemodynamic load, hereditary factors and inflammation. Ordinarily, we regard atherosclerosis as a degenerative disease, in recent decades, more and more reports have indicated that AS is a result of chronic inflammation. A lot of studies have proved cardiovascular disease, especially CHD are closely related to the elevation of inflammatory factors, such as tumor necrosis factor(TNF) and hyper sensitive-C reaction protein(hs-CRP).As one of the inflammatory cytokines mainly secreted by neutrophils and macrophages, interleukine-15(IL-15) has a variety of functions and participates in regulating many cellular processes. IL-15 and its receptors are constitutively expressed in activated T lymphocytes, B lymphocytes, NK cells and macrophoages.which induce secretion of inflammatory cytokines and promote proliferation and differentiation of lymphocytes and NK cells, and activate B lymphocytes to secret antibodies. Numerous studies have demonstrated the close association of IL-15 and atherosclerosis. IL-15 and its receptor are up-regulated in both human and animal atherosclerotic vulnerable lesions. Immunohistochemistry staining of human atherosclerotic plaques revealed that expressions of IL-15 in both smooth muscle cells and endothelial cells were increased, indicating that endogeneous IL-15 plays a critical role in the initiation and development of atherosclerosis. However, whether circulation IL-15 is related to cardiovascular diseases, especially CHD remains largely unknown, nor does the association between serum IL-15 and severity of coronary artery stenosis in CHD patients.Therefore, this study was aimed to explore the change of serum IL-15 in patients with CHD and its correlation with severity of coronary artery stenosis, in order to further explore mechanisms of CHD and to find novel therapeutic strategies.Objectives1.To detect the change of serum IL-15 level in patients with CHD compared with control subjects;2.To investigate the correlation of serum IL-15 level with severity of coronary artery, and further to determine the predictive value in predict the severity of coronary artery in patients with CHD.Methods1. A total of 180 hospitalized patients(125 males and 55 females) with coronary heart disease diagnosed in Department of cardiology of Xijing Hospital from August 2014 to November 2014, were admitted as subjects of experimental group of the study. The average age is 60.03±9.43 years old. 90 people undergone physical examination and coronary angiography(CAG) in Xijing Hospital who are diagnosed healthy or with neurosis were selected as control group. Information of subjects including blood pressure, body mass index and so on were collected.2. The experimental group was divided into the following subgroups according to lesion vessel numbers: single-vessle group, double-vessel group and three-vessel group.And according to the severity of coronary atery stenosis, the experimental group was devided into mild stenosis group,moderate stenosis group and severe stenosis group.3. 5ml of fasting venous blood was drawn into tubes in resting state, and promptly placed in Centrifuge at 3000 r/m to separate plasma. Then the separated plasma was stored in EP tubes and frozen at-80℃ until assay. Plasma IL-15 level was measured with Elisa method.4. CAG was performed by two experienced interventional cardiologists using normal Judkines method.5. Statistical analysis was performed with SPSS 18.0 statistics software. Measurement data were presented as x ± s, and categorical variables were expressed as frequencies or percentages. Comparisons between two groups of measurement data were performed by t test, and the χ2 test was used for two groups of categorical data. Comparisons among more than three groups were performed by one way ANOVA. Correlation analysis was performed with Pearson assay and stepwise regression analysis for analyzing independent factors. ROC curve was used to find out the meaningful level of IL-15. P<0.05 was considered statistically significant.Results1. Compared with control subjects, CHD patients were characterized with male, combination with hypertension, combination with diabetes, old ages, high Gensini score, high hs-CRP, high BMI and hyperlipidemia(all P﹤0.01). And the level of serum IL-15 was significantly increased in patients with CHD compared with control group(P﹤0.01).2. CHD patients were divided into subgroups according to lesion vessel numbers. There was significant difference of IL-15 level among these groups(P﹤0.01), and the serum IL-15 level was increased with the number of lesion vessels.3. CHD patients were divided into mild stenosis group, moderate stenosis group and severe stenosis group according to Gensini score. There was significant difference of IL-15 level among these groups(P﹤0.01), and with the deterioration of coronary artery stenosis the serum IL-15 level was increased.4. Pearson-related analysis revealed that serum IL-15 level was positively correlated with Gensini score, hs-CRP, TC, LDL and BMI(all P<0.01). Besides, multiple linear stepwise regression analysis revealed that Gensini score, TC 、 LDL,and BMI were independent indicators of IL-15 in CHD group.5. The corresponding area under the ROC curve were 0.976 and 0.961, and 95% confidence interval are(0.962~0.990)and(0.927~0.996).Conclusions1. The level of serum IL-15 level was significantly increased in patients with CHD compared with control grou, and IL-15 level was increased with the deterioration of coronary artery stenosis.2. Serum IL-15 level was positively correlated with Gensini score, hs-CRP, TG, LDLC and BMI, and negatively correlated with HDLC in patients with CHD. The serum IL-15 level may be helpful for predicting the severity of coronary artery in patients with CHD.