Effect of PCSK9 Inhibitors on Regulators of Lipoprotein Homeostasis, Inflammation and Coagulation

PCSK9 inhibitors (PCSK9i) represent a newer form of atherosclerosis treatment. Inflammation and haemostasis are key processes in the development of atherosclerosis. In this study, we investigated the influence of therapy with PCSK9i in patients with coronary artery disease (CAD) on regulators for lipoprotein homeostasis, inflammation and coagulation. Using quantitative polymerase chain reaction (qPCR) we measured the expression of the genes involved in lipoprotein homeostasis, namely for sterol regulatory element-binding protein 1 (SREBP1), SREBP2, low density lipoprotein receptor (LDLR), hepatic lipase type C (LIPC), LDLR-related protein (LRP8), and the genes associated with inflammation and coagulation, such as cluster of differentiation (CD) 36 (CD36), CD63 and CD14 in patients with CAD and healthy subjects. The results showed significant differences in the expression of the investigated genes between patients and healthy controls. Treatment with PCSK9i resulted in significant changes in the expression of all studied genes. Moreover, we found an association between changes in total cholesterol and SREBP1 expression, as well as a correlation between changes in HDL cholesterol and CD63 expression. To conclude, we established that PCSK9i may have a significant effect on the gene expression of lipid regulators, inflammatory markers and coagulation parameters, independent of their lipolytic effect.