Genetics of Atherosclerosis in Murine Models

Abstract

The pathology of atherosclerotic lesions that develop in mouse models of atherosclerosis, such as those lacking apolipoprotein E or lacking the low density lipoprotein receptor, is very similar to that seen in human patients. Consequently, genetic approaches to studying atherosclerosis in these mouse models have produced a wealth of information relevant to the genetic factors and pathways that modify the early stages of atherosclerosis in humans. Despite these advances, the later stages of atherosclerosis in humans, including spontaneous plaque rupture and hemorrhage, have not been observed reliably in current mouse models. Increasing sophistication and use of genetic manipulations, however, has produced significant advances in modeling these processes. The use of genetic tools to examine the physiology, pathology, and cell biology of atherosclerosis will enhance elucidation of the pathogenesis of the disease and lead to the development of novel therapeutic strategies.

Proteoglycan mediated lipoprotein retention: A mechanism of diabetic atherosclerosis

“…The most commonly used models include mice deficient in apoE, deficient in the LDL receptor, or transgenic for human apoB100. These models can all develop early atherosclerosis in weeks as compared to the decades required for human disease pathogenesis, and genetic manipulations in these models play a powerful tool for dissecting mechanistic pathways (for review see [76]). …”

Computational Stress Analysis of Atherosclerotic Plaques in ApoE Knockout Mice

“…1,3,8 The development of the apolipoprotein E knockout (KO) and LDL receptor-deficient mouse models in inbred mouse strains greatly accelerated the pace of our knowledge about molecules and cellular phenotypes that affect lesion growth. 11,24,38 The majority of these studies have focused on the development of the disease in the aorta which is the largest and the most accessible experimental vessel.…”

Bone marrow endothelial progenitors in atherosclerotic plaque resolution

“…6 Unfortunately, wellcharacterized atherosclerosis-prone mouse models such as low density lipoprotein receptor-deficient (Ldlr −/− ) and apolipoprotein E-deficient (ApoE −/− ) mice cannot be used for studies investigating plaque regression because genetic modifications in ApoE −/− and Ldlr −/− strains predispose these mice to irreversible diet-induced hyperlipidemia. 7 Unlike in humans, statins do not evoke constant dose-dependent and uniform cholesterol-lowering in ApoE −/− mice 8 and have variable, weak effects on cholesterol levels in Ldlr −/− mice.…”