1. Genetically Modified Models (LDLR Knockout Mice or ApoE Knockout Mice)

LDLR primarily recognizes ApoB on the surface of LDL particles and ApoE on the surface of IDL particles (apolipoprotein), mediating the internalization of these lipoproteins and their further metabolism within cells. Knockout of LDLR or ApoE genes leads to the inability of LDL, VLDL/IDL, etc., to bind to their respective receptors, resulting in delayed clearance of these lipoproteins and hyperlipidemia. Elevated blood lipids induce oxidative modification of lipoproteins, promoting the formation of AS lesions.

2. AAV-Induced AS Model (In-house Development)

PCSK9 is a key regulator in lipid homeostasis, with high expression levels in endothelial cells, vascular smooth muscle cells, and macrophages, exerting local effects on vascular homeostasis and atherosclerotic plaque formation. PCSK9 is primarily expressed in the liver. Hepatocytes bind PCSK9 via LDLR, forming a complex that is targeted for transport to lysosomes, leading to LDLR degradation. This disrupts the recycling pathway of LDLR on the cell membrane surface, hindering the clearance of LDLC from the body via LDLR transport, resulting in elevated plasma LDLC levels. It is currently recognized that the deposition of LDLC and other lipids in the arterial intima is a prerequisite for the development of AS in blood vessels.

Figure 2. PCSK 9 binding to LDLR on the hepatocyte surface (Alkindi M, et al. Can J Cardiol. 2016)

A single tail vein injection of AAV-PCSK9, combined with a high-fat diet, can rapidly induce AS in animals. Our company provides human and mouse overexpression AAV-PCSK9 and AS animal disease models. For more information, feel free to contact us!

Recommended injection and method: Administer 1-5E+11 vg of the virus via tail vein injection into the mouse, followed by a 12-week high-fat diet feeding before conducting tissue sampling for analysis.