Research Of The Relationship Between Urokinase-type Plasminogen Activator Receptor (uPAR) And Vulnerable Plaque

Background Acute coronary syndrome (ACS) is mainly caused by the fibrous cap rupture of vulnerable plaque and then local thrombosis. Recently, the mechanism of the formation of vulnerable plaque has not yet fully understood. Most researchers believe that rupture of the fibrous cap is due to extracellular matrix (ECM) more degradation than synthesis. Urokinase plasminogen activator receptor (uPAR), a cellular membrane glycoprotein receptor, participates in a variety of extracellular matrix degradation, after combined with urokinase plasminogen activator(uPA). Matrix metalloproteinase-9(MMP-9) is another protease associated with extracellular matrix degradation, it’s not clear the relationship between MMP-9and uPAR, which is the target of our research。Objectives The purpose was to study the relationship between uPAR and MMP-9during the formation of vulnerable plaque and to explore whether using of the level of uPAR of monocytes in peripheral vessels to predict the vulnerable plaque.Methods Animal experiment:immunohistochemistry was employed to detect the expression of uPAR as well as its association with MMP-9in different types of plaque, using the mice model of atherogenesis. Clinical Trials: Clinically acute coronary syndrome、stable angina、normal people with hyperlipidemia and normal subjects were enrolled in the study. The proportion of peripheral monocytes expressing uPAR was surveyed by flow cytometer, to observe differences among the four groups. For the ACS group, uPAR levels in peripheral monocytes were sequential detected before and after percutaneous coronary intervention (PCI) to observe the changes.Results Animal experiment:uPAR was detected in all stages of plaque, but the expression significantly increased in later vulnerable plaque, especially in the lipid pool, plaque shoulders, and rupture sites. MMP-9was almost undetectable in early plaques. however, the expression gradually increased from the middle to late plaques, and its distribution was similar with uPAR. Clinical Trials:1、ACS preoperative uPAR levels in peripheral monocytes was significantly higher than the other three groups; physical normal group was significantly lower than the other three groups, SAP group was no significant different with hyperlipidemic group.2、Hyperlipidemia might be a critical pair of factors activating uPAR expression.3、For ACS patients, uPAR levels during the first3days after PCI were significantly higher than the preoperative levels.3days later, uPAR levels gradually decreased.4、For ACS patients, the expression of uPAR with peripheral mononuclear cells, whose size and particle size were both larger, was higher than those ones, whose cell size and particle size are both smaller, especially in the fluorescence intensity. Conclusions uPAR play a role in very early stage of the pathogenesis of atherosclerosis. uPAR and MMP-9might be involved in the formation of vulnerable plaque. uPAR may be as one of clinical indicators of unstable stable angina.