Bisphenol A and Its Substitutes Show Proatherosclerotic Potential through the Dysregulation of CD36-Driven...

Bisphenol A (BPA) and its structural analogs are commonly found in consumer products, and concerns about their potential cardiovascular risks are growing. This study combined population data, cell and animal experiments, and molecular docking to explore the connection between bisphenol compounds (BPs) and atherosclerotic cardiovascular disease. In a cultured RAW264.7 macrophage model, environmentally relevant concentrations of BPs promoted lipid absorption and foam cell formation through the cluster differentiation 36 (CD36). In a male ApoE^-/- mouse model, BPs exposure increased aortic plaque burden. These effects were significantly reduced or eliminated in CD36-silenced cells and mice. Interestingly, BPA substitutes exhibited more potent effects than BPA itself. Molecular docking further supported the direct interaction between BPs and CD36, as well as the structure-toxicity relationship trend of these BPs. Overall, the findings suggest that BPs promote CD36-mediated lipid accumulation and the development of atherosclerosis. The study highlights the need to reevaluate the safety of BPs and provides a foundation for risk assessment and prevention strategies related to BPs exposure and cardiovascular disease.