Table 2.
Post-MI effects of perturbing extracellular matrix components
| Perturbation | Effect | Mechanism |
|---|---|---|
| Collagen type VI null (80) | ↓Infarct size | Accelerated acute apoptosis, ↓chronic apoptosis |
| ↑LV physiology | ||
| MMP and TIMP null | Improved LV remodeling | MMP-2: ↓M2 macrophage and myofibroblast activation |
| MMP-2 (40) | MMP-7: ↓connexin-43 cleavage, ↑conduction velocity | |
| MMP-7 (8, 70) | MMP-9: ↓macrophage accumulation (late phase) | |
| MMP-9 (18, 69) | MMP28: ↓inflammation and ↓M2 macrophage and fibroblast activation | |
| MMP-28 (82) | TIMP null: ↑MMP activity | |
| TIMP-1 (49) | ||
| TIMP-2 (59) | ||
| TIMP-3 (38, 115) | ||
| TIMP-4 (64) | ||
| Macrophage-specific MMP-9 transgenic (90) | ↑LV physiology | ↓Expression of other MMPs, ↑expression of profibrotic genes |
| ↓LV inflammation | ||
| Cardiac-specific MMP-1 transgenic (61) | ↑LV remodeling | ↑Collagen degradation |
| Osteopontin null (117) | ↓LV physiology, collagen deposition | ↑MMP-2 and ↓MMP-9 activity |
| Secreted protein acidic and rich in cysteine null (88, 104) | ↑LV physiology early; ↑rupture later | ↑Connective tissue growth factor activity and collagen synthesis |
| Thrombospondin-1 null (24) | ↑LV dilation, inflammation | ↓Transforming growth factor-β and Smad-2 signaling |
Reference numbers are listed in parentheses. MI, myocardial infarction; LV, left ventricular; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; ↑, increase; ↓, decrease.