HDL biology
A methodology review highlights the APOE*3-Leiden.CETP mouse as a model that closely mimics human lipoprotein metabolism (Vasc Biol 2024)
Original title: Atherosclerosis: an overview of mouse models and a detailed methodology to quantify lesions in the aortic root
This review covers the role of lipid metabolism and inflammation in atherosclerosis development and describes commonly used mouse models for studying the disease, alongside a detailed methodology for quantifying atherosclerotic lesion area in the aortic root. Following the development of apolipoprotein E knockout and LDL receptor knockout mice in the early 1990s, human APOE3-Leiden transgenic mice were generated and later cross-bred with human CETP transgenic mice to produce APOE3-Leiden.CETP mice. The review highlights that this combined model closely mimics human lipoprotein metabolism and responds to classic lipid-lowering interventions because it retains an intact ApoE-LDL receptor pathway for lipoprotein remnant clearance, making it a useful tool alongside other mouse models for atherosclerosis research, and provides a detailed protocol for scoring lesion severity based on American Heart Association guidelines adapted for mice.
Original abstract
Cardiovascular disease, the primary cause of human mortality globally, is predominantly caused by a progressive disorder known as atherosclerosis. Atherosclerosis refers to the process of accumulation of cholesterol-enriched lipoproteins and the concomitant initiation of inflammatory processes in the arterial wall, including the recruitment of immune cells. This leads to the formation of atherosclerotic plaques, initially causing a thickening of the arterial wall and narrowing of arteries. However, as plaque formation progresses, atherosclerotic plaques may become unstable and rupture, leading to a blood clot that blocks the affected artery or travels through the blood to block blood flow elsewhere. In the early 1990s, emerging gene editing methods enabled the development of apolipoprotein E knockout (Apoe-/- ) and low-density lipoprotein receptor knockout (Ldlr-/- ) mice. These mice have been instrumental in unraveling the complex pathogenesis of atherosclerosis. Around the same time, human APOE*3-Leiden transgenic mice were generated, which were more recently cross-bred with human cholesteryl ester transfer protein (CETP) transgenic mice to generate APOE*3-Leiden.CETP mice. This model appears to closely mimic human lipoprotein metabolism and responds to classic lipid-lowering interventions due to an intact ApoE-LDLR pathway of lipoprotein remnant clearance. In this review, we describe the role of lipid metabolism and inflammation in atherosclerosis development and highlight the characteristics of the frequently used animal models to study atherosclerosis, with a focus on mouse models, discussing their advantages and limitations. Moreover, we present a detailed methodology to quantify atherosclerotic lesion area within the aortic root region of the murine heart, as well as details required for scoring atherosclerotic lesion severity based on guidelines of the American Heart Association adapted for mice.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.