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bioRxiv · 10.1101/2023.03.07.531563

β-carotene accelerates resolution of atherosclerosis by promoting regulatory T cell expansion in the atherosclerotic lesion

Pinos, I.·Coronel, J.·Albakri, A.·Blanco, A.·McQueen, P.·Molina, D.·Sim, J.·Fisher, E. A.·Amengual, J.

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Abstract

{beta}-carotene oxygenase 1 (BCO1) catalyzes the cleavage of {beta}-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary {beta}-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that {beta}-carotene also accelerates atherosclerosis resolution in two independent murine models, independently of changes in body weight gain or plasma lipid profile. Experiments in Bco1-/- mice implicate vitamin A production in the effects of {beta}-carotene on atherosclerosis resolution. To explore the direct implication of dietary {beta}-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that {beta}-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of {beta}-carotene on atherosclerosis resolution. Our data highlight the potential of {beta}-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.

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Pinos, I., Coronel, J., Albakri, A., Blanco, A., McQueen, P., Molina, D., Sim, J., Fisher, E. A., Amengual, J.. 2023-03-10. β-carotene accelerates resolution of atherosclerosis by promoting regulatory T cell expansion in the atherosclerotic lesion. https://doi.org/10.1101/2023.03.07.531563

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