Schematic of the MMP2 and MMP9 systems. MMP2 is released in its pro form and cleavage by MT1-MMP leads to MMP2 activation. MT1-MMP is induced by furin and plasmin. TIMP2, tissue inhibitor of metalloproteinases 2, is an endogenous inhibitor of active MMP2. MMP3 is released in its pro form and cleavage leads to its activation. In turn, MMP9 is released in its pro form and MMP3 cleaves pro-MMP9 to produce active MMP9. Both pro-MMP3 and pro-MMP9 are induced by pro-inflammatory cytokines such as TNFα and IL-1β. TIMP1 is the endogenous inhibitor of active MMP9. Both MMP2 and MMP9 are known to degrade extracellular matrix proteins as well as tight junction proteins leading to vascular leakage and hemorrhage.