Platelet-associated metalloproteinases and inhibitors
| . | MKs . | Platelet granules . | Platelet membrane . | Interacts with . | Effect on platelet function . |
|---|---|---|---|---|---|
| ADAM10 | Yes | ND | Yes | Tetraspanins | Release of GPVI, APP |
| ADAM17 | Yes | ND | Yes | Release of GPIbα, GPV, Sema4D, APP, sCD40L? | |
| MMP-1 | Yes | Yes | Yes | αIIbβ3, PAR-1 | Accelerates thrombus formation |
| α2β1 | Primes platelets, cleaves PAR-1, activates platelet signaling | ||||
| MMP-2 | Yes | Yes | Yes | GPIb-IX-V | Increase thrombus formation, cleaves talin |
| αIIbβ3 | Cleaves PAR-1; release of sCD40L? | ||||
| MMP-3 | Yes | Unknown | |||
| MMP-9 | Yes | Yes/No | Yes | Decreased activation; reduced Ca2+ mobilization | |
| Increased thrombus area in MMP-9−\− mice | |||||
| MMP-13 | GPVI, αIIbβ3 | Impaired platelet aggregation to low dose collagen, CRP | |||
| Reduced thrombus formation | |||||
| MMP-14 | Yes | Yes | MMP-2 | Inhibits thrombus growth and stability | |
| TIMP-2 | |||||
| TIMP-1 | Yes | Yes | Inhibits platelet ADAMs? | ||
| TIMP-2 | Yes | Yes | MMP-14 | Synthesized de novo upon activation; inhibits all MMPs | |
| TIMP-3 | Yes | Inhibits platelet ADAMs? | |||
| TIMP-4 | ND |
| . | MKs . | Platelet granules . | Platelet membrane . | Interacts with . | Effect on platelet function . |
|---|---|---|---|---|---|
| ADAM10 | Yes | ND | Yes | Tetraspanins | Release of GPVI, APP |
| ADAM17 | Yes | ND | Yes | Release of GPIbα, GPV, Sema4D, APP, sCD40L? | |
| MMP-1 | Yes | Yes | Yes | αIIbβ3, PAR-1 | Accelerates thrombus formation |
| α2β1 | Primes platelets, cleaves PAR-1, activates platelet signaling | ||||
| MMP-2 | Yes | Yes | Yes | GPIb-IX-V | Increase thrombus formation, cleaves talin |
| αIIbβ3 | Cleaves PAR-1; release of sCD40L? | ||||
| MMP-3 | Yes | Unknown | |||
| MMP-9 | Yes | Yes/No | Yes | Decreased activation; reduced Ca2+ mobilization | |
| Increased thrombus area in MMP-9−\− mice | |||||
| MMP-13 | GPVI, αIIbβ3 | Impaired platelet aggregation to low dose collagen, CRP | |||
| Reduced thrombus formation | |||||
| MMP-14 | Yes | Yes | MMP-2 | Inhibits thrombus growth and stability | |
| TIMP-2 | |||||
| TIMP-1 | Yes | Yes | Inhibits platelet ADAMs? | ||
| TIMP-2 | Yes | Yes | MMP-14 | Synthesized de novo upon activation; inhibits all MMPs | |
| TIMP-3 | Yes | Inhibits platelet ADAMs? | |||
| TIMP-4 | ND |
Location of metalloproteinases and examples of their effects on platelet function. ? indicates proposed function that needs to be experimentally determined.
CRP, collagen-related peptide; MK, megakaryocyte; ND, not detected; PAR, protease-active receptor; Yes/No, conflicting reports.