The Role of Granzyme B Gene Expression in Coronary Heart Disease

Abstract

Cardiovascular disease, especially atherosclerotic CHD, remains the major cause of death worldwide. It was responsible for 30% of all global deaths in 2008. In Egypt, this ratio reached 39% of all death in the same year. Type 2 DM is characterized by increased risk for CVD. About 50% or more of diabetic patients die from CVD. This is believed to be a result of clustering of many risk factors comprising dyslipidemia, inflammation, IR and oxidative stress in diabetic patients. Atherosclerosis results from a complex interplay between circulating factors and various cell types in the vessel wall. Atherosclerotic lesions are characterized by accumulation of various innate and adaptive immune cells have deeply involved. Among these immune cells, CTLs represent major cells infiltrating advanced atherosclerotic lesions, highlighting the critical role of their mediators in atherogenesis. Granzyme B and perforin are the vital components of CTLs. Besides classical intracellular GZB/perforin pathway and its role in caspase-dependent and independent apoptosis of SMCs and ECs, GZB is now emerged as a fundamental mediator in many inflammatory diseases including CVD and type 2 DM. However, the contribution of GZB and perforin to underlying mechanisms associated with atherosclerosis is still far from full elucidation. Among huge members of serpins superfamily, PI-9 is the only known effective inhibitor of human GZB. Studies showed the unique ability of PI-9 to inhibit apoptosis and inflammation, critical processes in atherogenesis. Summary and Conclusions 114 However, the exact role of PI-9 in vasculature and modulating effect on atherosclerosis-associated key processes warrant further investigations. Hence, the current study was conducted as an attempt to investigate the expression of GZB, PI-9 and perforin genes in atherosclerosis with the impact of type 2 DM. Additionally, to explore the associations among these genes and their contribution to hallmarks of atherosclerosis including dyslipidemia, inflammation and IR.