Objective 
Protease 3 (PR3), a major neutrophil protease present in neutrophil azurophilic granule, is a multifunctional enzyme involved in the regulation of pro-inflammatory processes but its role in atherosclerosis remains unexplored. Here, we aimed to investigate whether PR3 is present in human atherosclerotic lesion and how it affects structure and functions of LDL and HDL.
Methods and Results
Normal and atherosclerotic coronary segments were collected from autopsy subjects and immunostained for PR3. Positive staining of PR3 was mainly detected in intima and adventitia of advanced atherosclerotic lesions. However, PR3 was neither detected in normal coronary arteries nor in coronary arteries characterized with atherosclerotic fatty streaks. Treatment of LDL with PR3 led to an extensive degradation of apoB-100, resulting in aggregation of LDL particles with enhanced binding to human aortic proteoglycans. In cultured human monocyte-derived macrophages uptake of the PR3-modified LDL particles was highly elevated, resulting in the macrophage transformation into foam cells. Moreover, incubation of HDL with PR3 resulted in proteolysis of major apolipoproteins (apoA-I, apoA-II and apoE) in the particles. Treatment of apoA-I or HDL with PR3 impairs their ability to promote cholesterol efflux from human macrophage foam cells. 
Conclusion
The present data demonstrate that PR3 is a novel protease found in human advanced atherosclerotic lesions and suggests that PR3 may have a role in the development of atherosclerosis by modifying both LDL and HDL particles.

01 - NEUTROPHIL PROTEASE 3 IS PRESENT IN HUMAN ATHEROSCLEROTIC LESIONS AND MODIFIES LDL AND HDL PARTICLES