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Fig. 1 | Arthritis Research & Therapy

Fig. 1

From: Tie2 as a novel key factor of microangiopathy in systemic sclerosis

Fig. 1

The role of Angiopoietins and Tie2 in vascular biology (adapted from [6,7,8, 11, 13, 14]). a In quiescent state, Ang-1, produced by pericytes, acts in a paracrine manner on the membrane-bound (mb) Tie2 receptor on endothelial cells (EC). The effects of Ang-1/Tie2 signalling ensure vessel stabilization. Ang-2, produced by EC, is stored in Weibel-Palade bodies. b In hypoxia and inflammation, Ang-2 is released from the Weibel-Palade bodies and acts in an autocrine manner on EC. Due to competitive binding to mbTie2, Ang-2 antagonizes Ang-1 signalling. In the absence of VEGF, the inhibition of Tie2 signalling leads to vessel destabilization and regression due to apoptosis of EC, loss of pericyte coverage and disrupture of the basement membrane. In the presence of VEGF, Ang-2 exerts pro-angiogenic effects with proliferation and migration of EC and sprouting of new branches. Additionally, VEGF causes shedding of Tie2. sTie acts as competitive ligand for Ang-1/-2 thereby blocking downstream signalling with anti-angiogenic effects. Ang Angiopoietin, VEGF vascular endothelial growth factor

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