Initial Research On The Expression Of IL-18 And MMP-9 In Atherosclerosis In Human Coronary Artery And Their Correlation With The Stability Of Plague

In recent years, attitudes towards atherosclerosis change from the simple lipid infiltration to active inflammatory process. The simplistic view of atherosclerosis as a pathophysiological disorder of passive lipid deposition has been redefined by the more complex concept of an active inflammatory response. Inflammation plays a crucial role in plaque formation, progress, thrombogenesis complication during which numerous inflammatory factors participate and relevant genes express. IL-18 has been idenitified as a multipotent cytokine so far and can induce mononuclear macrophage and T lymphocyte to secret IFN-γand contribute to the development and progression of atherosclerosis by direct and indirect stimulation of MMP-9 secretion.Aim: To detect mRNA and protein expression of IL-18 and MMP-9 and the correlation between them. To analyze the correlation between IL-18, MMP-9 and atherosclerosis for clinical diagnosis, treatment and prognostic evaluation of atherosclerosis in the future.Methods: Considering the medical history and gross observation of 14 autopsy cases, they were classified as 5 normal cases and 9 atherosclerosis coronary artery. Disconnect the left coronary artery and right coronary. The samples were divided into four different groups, designated as unstable plague groups (16 samples), stable plague groups (21 samples), non plague region in atherosclerosis (6 samples) and normal atherosclerosis(5 samples). non plague region in atherosclerosis and normal atherosclerosis are considered as normal groups. These specimens were detected by immunohistochemistry, RT-polymerase chain reaction, locate macrophage (CD-68) and smooth muscle cell(α-actin) in the plague. Rank test, chisquare test and Spearman test are applied in statistics treatment.Results:(1)IL-18 and MMP-9 mRNA expression can be detected in atherosclerosis, and there is significant difference between unstable plagues and stable plagues(PIL-18=0.028, PMMP-9=0.036). The levels are higher in unstable plagues. No expression exists in control group. Positive association showed between IL-18 mRNA expression and MMP-9 mRNA expression in atherosclerosis by Spearman tests(rs=0.375, P=0.022).(2)Immunohistochemistry: Il-18 protein can be tested in endomembrane of atherosclerosis coronary artery, mainly in macrophage, foam cells and relatively less expressed in fibrocyte, endothelial cell, smooth muscle cell in endomembrane, while hardly exists in smooth muscle cell of tunica media. In control groups, no expression can be detected. There is significant difference between unstable plague and stable plagues (P=0.028) and higher level manifested in unstable ones. MMP-9 protein expression can be observed in atherosclerosis, mainly in macrophage, foam cells, nucleus and perinuleus of both fibrocyte and endothelial cell, smooth muscle cell in endomembrane, smooth muscle cell and fibrocyte in tunica media. Expression difference exists both endomembrane(P=0.012) and tunica media(P=0.033). In control groups, no expression can be detected. MMP-9 expression level is higher in unstable plagues than that in stable ones. Positive associations between IL-18 and MMP-9 expression intensity showed in Spearman tests(rs=0.401, P=0.014).(3)IL-18 and MMP-9 mRNA expression and protein expression level are parallel on the whole.Conclusion:(1) IL-18 and MMP-9 expression can be tested in atherosclerosis and expression level is higher in unstable plagues than stable ones, while no expressions exist in control group. This indicates IL-18 and MMP-9 both participate in the initiation and development of atherosclerosis and are highly relevant to the unstable plague.(2) Positive association between IL-18 and MMP-9 on the perspective of mRNA or protein level indicates that IL-18 is in coordination with MMP-9 during the development of atherosclerosis.