Development of a Humanized Mouse Model of Atherosclerosis.

Margot Evans

Document Type

Article

Publication Date

2025

Keywords

JMG

Abstract

Atherosclerosis remains a leading cause of mortality, driven by complex interactions between lipid metabolism and immune-mediated inflammation. While current mouse models such as Apoe⁻/⁻ mice have advanced our understanding of disease mechanisms, species-specific immune differences limit their translational relevance. In this study, we worked toward the development of a humanized model of atherosclerosis using NSG-Apoe⁻/⁻ mice engrafted with human CD34⁺ hematopoietic stem cells (HSCs) to develop both lipid-driven aortic plaque formation and human immune cell involvement. Mice were subjected to either a high-fat diet or normal chow, and disease progression was assessed through serum lipid profiling, histological analysis of aortic plaques, and immune cell characterization by flow cytometry and immunofluorescence microscopy. NSG-Apoe⁻/⁻ mice fed a high-fat diet exhibited elevated serum LDL and total cholesterol levels, plaque formation, and infiltration of human immune cells across tissues. These findings demonstrate steps toward the use of a humanized Apoe⁻/⁻ model for investigating human immune contributions to atherosclerosis, offering a valuable platform to understand human-specific mechanisms of disease progression and immune involvement.

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