A. Armani, V. Marzolla, C. Mammi, L. Vitiello, E. Bellucci, A. Feraco, S. Gorini, et al. (2026). Protective effects of ketogenic diet on aldosterone-induced atherosclerosis in ApoE-/- mice. Journal of endocrinological investigation, 49(2), 435-442. https://doi.org/10.1007/s40618-025-02740-z

PubMed 41196563

[Abstract]
PURPOSE: Atherosclerosis represents the main determinant of major adverse cardiovascular events and cardiovascular death, and a large body of evidence demonstrated that circulating aldosterone (Aldo) levels contribute to the development of atherosclerosis. Ketogenic diets have gained attention for their efficacy in weight reduction and metabolic control. This study aims to investigate the potential of this dietary regimen to counteract plaque formation in a mouse model of atherosclerosis stimulated by Aldo.

METHODS: Male 9-week-old ApoE-/- mice were implanted with an osmotic minipump subcutaneously containing vehicle or Aldo (6 μg/mouse/day) and placed either on an atherogenic high fat diet (HFD, 4.5 kcal/g, 42% Kcal from fat) or on a ketogenic diet (KD, 6.8 kcal/g, 90.5% Kcal from fat) for 4 weeks. After treatment, mice were sacrificed and the aortic tissues were collected for histochemical and gene expression analyses to investigate atherosclerotic plaque size and composition as well as transcript levels of markers involved in the atherosclerotic process.

RESULTS: KD effectively reduced plaque size and lipid content in Aldo-treated mice, as compared with HFD. In addition, aortas of KD-fed mice showed decreased levels of pro-inflammatory markers like ICAM-1, VCAM-1, MCP-1, IL-6, and TNF-α, and displayed a macrophage polarization towards an anti-inflammatory M2 profile.

CONCLUSIONS: The findings show that KD counteracts atherosclerosis development induced by Aldo in ApoE-/- mice, suggesting that KD may prevent atherosclerotic plaque formation in subjects with high cardiovascular risk.