ABSTRACT
ß-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of ß-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 ß-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that ß-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 ß-carotene on atherosclerosis resolution. To explore the direct implication of dietary ß-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that ß-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of ß-carotene on atherosclerosis resolution. Our data highlight the potential of ß-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.
Subject(s)
Atherosclerosis , beta Carotene , Mice , Humans , Animals , beta Carotene/pharmacology , beta Carotene/metabolism , Vitamin A/metabolism , Liver/metabolism , Atherosclerosis/drug therapy , Atherosclerosis/metabolism , LipidsABSTRACT
ß-carotene oxygenase 1 (BCO1) catalyzes the cleavage of ß-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 ß-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models. Here we show that ß-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 ß-carotene on atherosclerosis resolution. To explore the direct implication of dietary ß-carotene on regulatory T cells (Tregs) differentiation, we utilized anti-CD25 monoclonal antibody infusions. Our data show that ß-carotene favors Treg expansion in the plaque, and that the partial inhibition of Tregs mitigates the effect of ß-carotene on atherosclerosis resolution. Our data highlight the potential of ß-carotene and BCO1 activity in the resolution of atherosclerotic cardiovascular disease.
