Pitfalls in the assessment of murine atherosclerosis

Abstract

This review provides examples of the fact that different procedures for the measurement of atherosclerosis in mice may lead to interpretation of the extent of atherosclerosis having markedly different biological and clinical significance for humans: 1) aortic cholesterol measurement is highly sensitive for the detection of early and advanced atherosclerosis lesions, but misses the identification of the location and complexity of these lesions that are so critical for humans; 2) the histological analysis of the aortic root lesions in simvastatin-treated and control mice reveals similar lesion morphology in spite of the remarkable simvastatin-induced reduction of the aortic cholesteryl ester content; 3) in histological analyses, chemical fixation and inclusion may extract the tissue fat and also shrink and distort tissue structures. Thus, the method may be less sensitive for the detection of slight differences among the experimental groups, unless a more suitable procedure employing physical fixation with histological sample freezing using optimal cutting temperature and liquid nitrogen is employed. Thus, when measuring experimental atherosclerosis in mice, investigators should be aware of several previously unreported pitfalls regarding the extent, location and complexity of the arterial lesion that may not be suitable for extrapolation to human pathology.

Hypercholesterolemia in pregnant mice increases the susceptibility to atherosclerosis in adult life

“…Numerous epidemiological studies confirm hyperlipidemia as the most important biological risk factor for atherosclerosis in many laboratory animal models of atherosclerosis-involving wild-type, naturally defective or genetically modified animals. [2][3][4] Transgenic animals provide major advantages such as a clean genetic background and rapid induction of atherosclerosis. The apolipoprotein E (apoE) knockout mouse is the first widely used and one of the most wellcharacterized genetically manipulated models for atherosclerosis research.…”

“…Numerous epidemiological studies confirm hyperlipidemia as the most important biological risk factor for atherosclerosis in many laboratory animal models of atherosclerosis-involving wild-type, naturally defective or genetically modified animals. 2–4…”