APOE and obesity due to melanocortin 4 receptor deficiency: While the existing literature indicates contribution of different vascular cell types (SMC, EC, macrophages) to leptin-induced atherogenesis, more systematic approaches using cell-specific LepR knockouts and lineage tracing strategies in the background of atherosclerotic models (ApoE-/-, LDL-R-/-) are required to elucidate the fundamental molecular mechanisms by which hyperleptinemia drives lesion pathogenesis in obesity and related metabolic complications.