We have previously shown that endothelial cell matrix metalloprotease 12 (MMP12) and pentraxin 3 (PTX3) overproduction is the main alteration accounting for reduced proneness to angiogenesis in systemic sclerosis (SSc).
In systemic sclerosis (SSc) microvascular endothelial cells (MVECs), angiogenesis is blocked by matrix metalloproteinase 12-dependent cleavage of domain 1 of the urokinase-type plasminogen activator receptor (uPAR).
Loss of function of MMP12 and PTX3 in SSc MVECs restores the ability of the cells to produce capillaries in vitro and induces vascularization in vivo on a Matrigel sponge.