The Apoe(-/-) mouse model: a suitable model to study cardiovascular and respiratory diseases in the context of cigarette smoke exposure and harm reduction

Abstract

Atherosclerosis-prone apolipoprotein E-deficient (Apoe(-/-)) mice display poor lipoprotein clearance with subsequent accumulation of cholesterol ester-enriched particles in the blood, which promote the development of atherosclerotic plaques. Therefore, the Apoe(-/-) mouse model is well established for the study of human atherosclerosis. The systemic proinflammatory status of Apoe(-/-) mice also makes them good candidates for studying chronic obstructive pulmonary disease, characterized by pulmonary inflammation, airway obstruction, and emphysema, and which shares several risk factors with cardiovascular diseases, including smoking. Herein, we review the results from published studies using Apoe(-/-) mice, with a particular focus on work conducted in the context of cigarette smoke inhalation studies. The findings from these studies highlight the suitability of this animal model for researching the effects of cigarette smoking on atherosclerosis and emphysema.

Keywords: Apoe; Atherosclerosis; COPD; Cigarette smoke; Emphysema; Lipoprotein; Mouse model; Tobacco heating system.

Fig. 1

Overview of the pathophysiological events and endpoints in the context of inhalation toxicology studies in Apoe^−/− mouse model. BALF broncho-alveolar lavage fluid. COPD chronic obstructive pulmonary disease

Fig. 2

Lipid imbalance together with endothelial dysfunction and systemic inflammation determine the development of atherosclerosis as well as lung inflammation in Apoe^−/− mice (and humans). CS exposure enhances these processes, thereby increasing oxidative stress and inflammation processes

Fig. 3

Lipoprotein structure and abundance in humans, wild type, and Apoe^−/− mice plasma. a The general structure of a lipoprotein includes a hydrophobic central core consisting of triglycerides, fatty acids, and esterified cholesterol, and a surface monolayer of phospholipid, free cholesterol, and specific apolipoproteins. b Schematic representation of cholesterol and triglycerides (TG) abundance in the different plasma lipoprotein species among humans, wild type, and Apoe^−/− mice

Fig. 4

Aortic arch lipids from exposed Apoe^−/− mice vs sham controls shared with the human plaque-enriched lipids reported by Stegemann et al. [126]. Differential abundance profiles for lipid species with significant differential abundance in any exposure to sham comparison (*BH-adjusted p value < 0.05). The x-axis and the color code indicate the log₂ (Fc)