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Matrix Metalloproteinase‐9 Inhibition Attenuates Wall Thinning but Increases Neutrophil Infiltration Post‐Myocardial Infarction in Mice
Author(s) -
IYER RUGMANI PADMANABHAN,
PATTERSON NICOLLE LYANNE,
FIELDS GREGG B,
LINDSEY MERRY L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.646.10
Subject(s) - eotaxin , medicine , saline , myocardial infarction , matrix metalloproteinase , infiltration (hvac) , inflammation , chemokine , ligation , thermodynamics , physics
Targeted deletion of the matrix metalloproteinase‐9 (MMP‐9) gene attenuates cardiac remodeling post‐myocardial infarction (MI), but whether MMP‐9 inhibition post‐MI is effective as a therapeutic strategy has not been evaluated. Adult male C57BL/6 mice (3–6 months old, n=80) were subjected to left coronary artery ligation. Osmotic pumps with saline or MMP‐9 inhibitor (MMP‐9i; 0.03 μg/day) were inserted subcutaneously 3h post‐MI, and the mice were sacrificed at day 7 post‐MI. Infarct area was similar in the saline (57±2%) and MMP‐9i (55±1%, p=0.22) groups, indicating similar initial injury. Survival rates were 33% (12/36) for saline and 27% for the MMP‐9i (12/44; p=0.54). Infarct wall thinning was lower in the MMP‐9i group (0.95±0.10 mm) vs. saline (0.66±0.08 mm; p=0.04). Out of 84 inflammatory genes examined in the infarct region, 13 pro‐inflammatory and 2 anti‐inflammatory genes were increased in the MMP‐9i group, indicating an overall increase in inflammation. One upregulated cytokine was Ccr3, the eotaxin receptor that regulates neutrophil influx. Eotaxin was also 1.5 fold increased in the plasma of the MMP‐9i mice. Further, neutrophil numbers were 10× higher in the MMP‐9i group at day 7 post‐MI, indicating prolonged neutrophil presence in the infarct region. In conclusion, MMP‐9 inhibition post‐MI attenuated LV wall thinning and facilitated neutrophil infiltration through increased eotaxin levels.