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MMP-PAR1 signaling in vascular diseases. PAR1 senses a diverse milieu of extracellular proteases and subsequently relays that information to influence cellular behavior and potentially exacerbate disease pathologies. The N-terminal extracellular domain (exodomain) of PAR1 is cleaved at a canonical site by thrombin and noncanonical sites by MMP-1 and MMP-13. Various signaling outputs can lead to platelet thrombosis, atherosclerosis, in-stent restenosis, heart failure, and sepsis.
