LRP1 in atherosclerosis: a hierarchical view of regulatory mechanisms and epigenetic knowledge gaps

Abstract

Inflammation is a central driver of vascular dysfunction and plays a pivotal role inthe initiation and progression of atherosclerosis. This chronic inflammatorycondition arises from complex molecular, cellular, and epigenetic interactionswithin vascular and immune networks. Monocytes and macrophages act as keymediators of plaque development, integrating lipid handling and inflammatorysignaling. Low-density lipoprotein receptor-related protein 1 (LRP1) has emergedas a multifunctional receptor at the interface between lipid metabolism andimmune regulation, modulating Toll-like receptor pathways and inflammatoryresponses in a context-dependent manner. Here, we review current evidence onthe regulatory mechanisms controlling LRP1 expression and propose ahierarchical framework in which transcription factor-mediated and non-codingRNA-mediated mechanisms represent the most strongly supported layers ofregulation. In contrast, although epigenetic processes broadly influencevascular inflammation, direct chromatin-level interrogation of the LRP1 locusremains limited. Together, this framework highlights key knowledge gaps andprovides a conceptual basis for understanding how multi-layered regulation ofLRP1 contributes to vascular inflammation and plaque progression.