Smooth muscle mineralocorticoid receptor and atherosclerosis in male and female ApoE-knockout mice
In ApoE-knockout mice on 8 weeks of high-fat diet, deleting the mineralocorticoid receptor in smooth muscle cells changed neither classic cardiovascular risk factors nor early plaque size or composition, in males or females. [1]
Automatic summary · not editorially reviewed
The key findings
The source at a glance
- Study type / format
- Preclinical animal study (mouse genetic knockout experiment)
- Population / context
- Male and female ApoE-knockout mice with smooth muscle cell–specific MR deletion and littermate controls with intact MR, fed a high-fat diet for 8 weeks.
- Summary based on
- Study abstract
- Original publication
- October 15, 2026
Sex differences in plaque and the untested female mice
Young women have a lower risk of myocardial infarction than age-matched men, and this protection is lost with aging or obesity. Human plaques differ by sex: male plaques are described as more inflamed, female plaques as having more smooth muscle cell content. The hormone aldosterone activates the mineralocorticoid receptor (MR). In earlier cell-type-specific knockout work, deleting MR in smooth muscle cells did not affect plaque phenotype in male mice, but female mice had never been studied. This study tested the role of smooth muscle cell MR in atherosclerosis for the first time in female mice, comparing male and female littermates.
Supporting source [1]
ApoE-knockout mice with smooth muscle MR deletion, 8 weeks high-fat diet
The researchers crossed ApoE-knockout mice with mice carrying a floxed MR gene and a smooth muscle cell–specific, tamoxifen-inducible Cre, producing ApoE-knockout mice with smooth muscle cell MR deletion and littermate controls with intact MR. Reduced MR messenger RNA in the aorta was confirmed in both sexes. After 8 weeks of high-fat diet, they measured aldosterone levels, blood pressure, fasting glucose and cholesterol, and body weight, and examined aortic root sections histologically for plaque size and composition.
Supporting source [1]
No effect on risk factors or early plaque in either sex
The smooth muscle cell MR deletion did not significantly affect aldosterone levels, blood pressure, fasting glucose and cholesterol, or body weight, although males weighed significantly more than females. It did not significantly change aortic root plaque area in males or females, although females had larger plaques than males. There were no significant sex or genotype differences in the percentage of plaque made up of necrotic core or neutral lipids, and no impact on the percentage composed of fibrosis. Staining for smooth muscle actin or Mac2 in plaque also showed no impact of the deletion. The authors conclude that in this early atherosclerosis model, smooth muscle cell MR did not affect these outcomes in either sex.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a mouse model of early atherosclerosis (8 weeks of high-fat diet), so results may not apply to humans or to longer disease courses. Only the abstract's reported outcomes are described.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Svedberg NL, An W, Tan S, Jaffe IZ. · europepmc.org · October 15, 2026