apoE

Apolipoprotein E (ApoE) is a key regulator of lipoprotein metabolism that mediates the hepatic clearance of diet-derived chylomicron remnants and liver-derived very-low-density lipoprotein (VLDL) remnants through interactions with members of the low-density lipoprotein receptor family^[1][2]. ApoE deficiency disrupts this clearance pathway, resulting in marked hypercholesterolemia, accumulation of remnant lipoproteins, and enhanced susceptibility to atherosclerotic lesion formation^[1][3][4]. Mechanistically, ApoE regulates cholesterol homeostasis and influences macrophage biology, linking lipid metabolism to vascular inflammation and atherogenesis^[2][5]. In disease models, Apoe^−/− mice develop spontaneous atherosclerosis even when maintained on a low-cholesterol diet and therefore represent one of the most widely used experimental systems for investigating cardiovascular disease mechanisms and therapeutic interventions^[3][4][6]. Atherosclerotic lesions in these mice progress in a manner that reproduces many pathological features of human disease, making the model highly valuable for studies of plaque development and progression^[6][7]. Compared with related human APOE isoforms, ApoE deficiency represents a complete loss-of-function state rather than an isoform-specific alteration, providing a robust platform for dissecting the physiological roles of ApoE in lipoprotein transport, monocyte/macrophage biology, and atherosclerosis^[2][5]. For experimental applications, the Apoe^−/− model is extensively used to evaluate genetic, nutritional, and pharmacological factors that modify atherosclerotic burden and vascular inflammation^[6][7][8].