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Updated: Jun 23, 2026
Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
Sexual dimorphism in atherosclerotic plaques of aged Ldlr-/- mice
Virginia Smit1, Jill de Mol1, Mireia N A Bernabé Kleijn1
1LACDR, Leiden Academic Centre for Drug Research, Division of BioTherapeutics, Leiden University, Einsteinweg 55, 2333CC, Leiden, The Netherlands.
Sex significantly impacts atherosclerosis, with female mice exhibiting heightened immune cell infiltration and pro-inflammatory responses in plaques, while males show increased CD8+ T cells and specific macrophage populations. This highlights sex as a key factor in cardiovascular disease development.
Area of Science:
- Immunology
- Cardiovascular Biology
- Sex Differences in Disease
Background:
- Atherosclerosis is a chronic inflammatory disease driven by lipid accumulation and immune responses in the vascular wall.
- Sex influences atherosclerosis prevalence and manifestation, but high-resolution immune landscape differences remain understudied.
- This study investigates sex-specific immunological differences in atherosclerotic aortas at a single-cell level.
Purpose of the Study:
- To elucidate sex-specific immunological differences in the atherosclerotic plaque environment.
- To compare plaque morphology and immune cell composition between male and female mice.
- To identify distinct immune cell populations and activation pathways influenced by sex in atherosclerosis.
Main Methods:
- Histological analysis of atherosclerotic plaques in aged male and female Ldlr-/- mice.
- Single-cell RNA-sequencing of aortic immune cells (CD45+) to profile the immune landscape.
- Flow cytometry to quantify and characterize immune cell populations and phenotypes.
Main Results:
- Plaque volume was similar, but female aortas had more collagen, cholesterol crystals, and less necrotic core than males.
- Female aortas showed increased immune cell infiltration, with enriched pro-atherogenic markers and inflammatory pathways.
- Female mice displayed enhanced B cell activation and an increased M1/M2 macrophage ratio with a pro-inflammatory phenotype; males had more CD8+ T cells and Trem2+ macrophages.
Conclusions:
- Sex is a critical variable influencing immunological differences within atherosclerotic plaques.
- Findings provide high-resolution insights into sex-specific immune responses in atherosclerosis.
- This research informs future preclinical studies on sex-based cardiovascular disease pathophysiology.
