Functional analysis of the candidate gene(s) that is considered to play role in coronary artery disease

Coronary artery disease (CAD), which is characterized by the formation of atherosclerotic plaque in arteries carrying food and oxygen to the heart, is one of the most important public health problems both in our country and in the world. Since atherosclerosis is often preventable, it is of utmost importance to elucidate the underlying mechanisms and, therefore, risk factors. It is thought that increased lipid peroxidation and tissue damage with iron overload, which is one of the main factors of the newly defined programmed cell death -ferroptosis-, can lead to atherosclerosis and diabetes. Therefore, the aim of this thesis project is to investigate the mechanisms involved in the formation of ferroptotic cell death and CAD. For this purpose, RTN3, CAT, SLC25A1, HMOX-1, GPX4, ACSL4 and SLC7A11 genes were selected and their roles in these mechanisms were investigated. In this study, ferroptosis in HEPG2 cells was induced by erastin and inhibited by ferrostatin-1. The conditions which ferroptosis is induced and both inducer and inhibitor-containing conditions were examined for the viability of cells and gene expressions of candidate genes. While the expression of RTN3, CAT, SLC25A1 and GPX4 were observed to be decreased, HMOX-1 and SLC7A11 gene expressions were increased and ACLS4 expression did not change. When the expression levels of the selected genes were compared in patients with CAD and non-CAD individuals, it was observed RTN3, CAT, and SLC25A1 expressions changed significantly. Changes in expression of selected genes after induction of ferroptotic cell death with erastin suggest that these genes may be important candidates for the mechanism. In this research which aims for the investigation of the effect of ferroptosis on the pathogenesis of atherosclerosis, new targets which may play roles in both mechanisms are identified.