ANGPT2 and rheumatoid arthritis: For example, the Notch signaling pathway has been shown to mediate hypoxia-induced angiogenesis in inflammatory arthritis via the interaction of Notch-1/HIF-1 through VEGF/Angiopoietin-2 (Gao et al., 2012) In addition, pro-inflammatory mediators are also able to promote RA angiogenesis, including cytokines [e.g., IL-17, IL-18, and macrophage migration inhibitory factor (MIF)], chemokines (CXCL12), growth factors (e.g., Ang1 and Ang2), proteases (MMPs), and adhesion molecules (e.g., ICAM-1 and VCAM-1; Elshabrawy et al., 2015).