PCSK9 and lipid metabolism and atherosclerosis: Animal models

Abstract

PCSK9 is a secreted protein that binds to the LDL receptor on the cell surface, is endocytosed along with the receptor, and interferes with its ability to recycle to the cell surface. Instead the receptor is directed to the lysosome where it is degraded, leading to decreased levels of the receptor on the cell surface and decreased internalization of LDL. In this review, we will discuss how mice deficient in the Pcsk9 gene or hepatic overexpression due to transgenesis or viral vector mediated expression contributed to our understanding of the in vivo role of PCSK9. In addition, we will discuss how the discovery of PCSK9 and its gain of function mutants has greatly facilitated the manipulation of animals modelling atherosclerosis to induce hypercholesterolemia and atherosclerosis.