Relapse of pathological angiogenesis: functional role of the basement membrane and potential treatment strategies

摘要

a Simplified schematic illustration of the VEGF family ligands VEGF-A, -B, -C, and -D interacting with their receptors VEGR-1, -2 and -3 to drive lymphangiogenesis and angiogenesis. Neuropilin receptors (NRP1 and NRP2) enhance VEGF signaling by acting as coreceptors for VEGFR-1 and VEGFR-2. b Angiogenesis, the growth of new blood vessels from pre-existing vessels, is regulated mainly by the VEGF signaling pathway. Growth factors in the VEGF family, such as VEGF-A, VEGF-C, VEGF-D, and PlGF, as well as other factors, such as the fibroblast growth factor (FGF) family, angiopoietin-1 (Ang-1), and MMPs, are important for the sprouting of new vessels. The newly formed blood vessels are initially leaky but over time undergo maturation characterized by deposition of BM pericyte and mural cell coverage, regulated by pathways such as PDGF-B signaling via PDGFR-B and ANG-1 signaling via Tie2, and TGF-β133. Mature blood vessels are maintained in a functional state by factors such as VEGF-B. Under pathological conditions, such as in the tumor microenvironment, these processes are dysregulated, leading to poorly developed vessels that leak fluid and form a disorganized vascular network134.