FIGURE 4.

The involvement of inflammatory cells in bAVM growth. Macrophages release VEGF, which regulates the development of ECs and vessel sprouting. By generating matrix proteases, macrophages degrade ECM to create a guiding pathway for proliferation and migration of ECs and facilitating vascular branching. Macrophages also have crucial role in recruitment of pericytes around new blood vessels by expressing high levels of PDGFB. Macrophages through triggering autocrine feedback loop of COX2, PGE2, EP2-NF-kB-COX2 results in bAVM prograssion. Likewise, macrophages express TLR4, which binds to myeloid differentiation primary response gene 88 (MyD88) and leads to the generation of complex with IRAKs and activation of inhibitor kappa B kinase β (IKKβ). This process leads to translocation of NF-κB into the macrophage nucleus and overexpressing genes involved in inflammation. ECs: endothelial cells, COX2: cyclo-oxygenase 2, PGE2: Prostaglandin E2- EP2: prostaglandin E receptor subtype 2, MyD88: myeloid differentiation primary response gene 88, PDGFB: Platelet-derived growth factor B, TLR4: toll-like receptor 4, IRAKs: IL-1R-associated kinases, IKKβ: inhibitor kappa B kinase β.