. Author manuscript; available in PMC: 2019 Aug 1.

Published in final edited form as: Nat Rev Cardiol. 2018 Aug;15(8):471–479. doi: 10.1038/s41569-018-0022-z

Table 2 |.

Evidence for MMP9 involvement in cardiac remodelling after MI¹¹

Criteria	Evidence
Criterion 1: MMP9 levels increase after MI	Increased in plasma (mice and humans)^77–79 Increased in left ventricular infarct area (mouse, rat, hamster, rabbit, sheep, pig, dog, and human)^{18,24,80–86} Increased in cardiac lymph (dog)¹⁸
Criterion 2: MMP9 inhibition or overexpression has effects on cardiac remodelling	Genetic deletion: improves left ventricular physiology and remodelling after MI, improves age-related cardiac dysfunction, and attenuates angiotensin II-induced cardiac fibrosis^80,87,88 Macrophage-specific overexpression improves left ventricular physiology and remodelling after MI in adult and aged mice²⁵ Global MMP inhibition improves cardiac remodelling, but early pharmacological MMP9 inhibition (3 h after MI) worsens cardiac remodelling^24,89
Criterion 3: MMP9 actions can be mimicked in vitro by MI-relevant cell types	Decreased neutrophil apoptosis²⁴ Decreased macrophage phagocytic capacity^24,26
Criterion 4: Proteolysis of MMP9 substrates modulates cardiac remodelling	C-1158/59 (a collagen-derived matricryptin) is protective in cardiac remodelling after MI²¹

MI, myocardial infarction; MMP, matrix metalloproteinase.