Manganese therapy for dyslipidemia and plaque reversal in murine models.

Precise control of circulating lipid levels is vital in both health and disease. We recently uncovered that bulk lipids, transported by lipoproteins, enter the circulation initially via the coat protein complex II (COPII) in a condensation-dependent manner. Divalent manganese, acting as a signaling messenger, selectively controls COPII condensation to regulate lipid homeostasis in vivo. Here, we present evidence for a manganese-based therapy in murine models of hypolipidemia and hyperlipidemia, aided by advanced in vivo multimodal imaging of atherosclerosis. Dietary titration of manganese supply enables tailored control of circulating lipid levels in whole animals, with no apparent toxicity. Strikingly, elevating the manganese signal through diets could not only effectively treat pathological hyperlipidemia but also further achieve significant reversal of atherosclerotic plaques. Hence, the study provides critical proof-of-principle for a novel therapy for deadly cardiovascular diseases with a potentially broad impact.