Cardiovascular diseases remain the leading cause of mortality, with the majority of deaths resulting from atherosclerotic complications. The initiation of atherosclerosis is closely associated with lipid accumulation in the arterial wall, which is directly dependent on systemic lipoprotein levels. The project represents a continuation of our research following our discovery of the hepatic cycle of very low-density lipoproteins (VLDL cycle), which constitutes a critical regulatory point in systemic lipoprotein homeostasis. We aim to identify biomarkers of VLDL cycle dysfunction as well as potential therapeutic targets for modulating the lipoprotein profile and reducing atherosclerotic complications. By using advanced 3D liver models, targeted interventions in murine models, and a human clinical study, we will identify biomarkers of VLDL cycle dysfunction as well as potential therapeutic targets for modulating the lipoprotein profile and reducing atherosclerotic complications.