The molecular mechanism of LRP1 in physiological vascular homeostasis and signal transduction pathways

Interactions between vascular smooth muscle cells (VSMCs), endothelial cells (ECs), pericytes (PCs) and macrophages (MФ), the major components of blood vessels, play a crucial role in maintaining vascular structural and functional homeostasis. Low-density lipoprotein (LDL) receptor-related protein-1 (LRP1), a transmembrane receptor protein belonging to the LDL receptor family, plays multifunctional roles in maintaining endocytosis, homeostasis, and signal transduction. Accumulating evidence suggests that LRP1 modulates vascular homeostasis mainly by regulating vasoactive substances and specific intracellular signaling pathways, including the plasminogen activator inhibitor 1 (PAI-1) signaling pathway, platelet-derived growth factor (PDGF) signaling pathway, transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The aim of the present review is to focus on recent advances in the discovery and mechanism of vascular homeostasis regulated by LRP1-dependent signaling pathways. These recent discoveries expand our understanding of the mechanisms controlling LRP1 as a target for studies on vascular complications.