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Matrix metalloproteinase‐28 deletion attenuates early cardiac dysfunction following myocardial infarction by restraining neutrophil infiltration and limiting the inflammatory response
Author(s) -
Ma Yonggang,
Yabluchanskiy Andriy,
Zhang Jianhua,
Ramirez Trevi A.,
Manicone Anne M.,
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.386.12
Subject(s) - myocardial infarction , medicine , ejection fraction , infiltration (hvac) , matrix metalloproteinase , cardiac rupture , inflammation , cardiac function curve , endocrinology , chemokine , cardiology , immunology , heart failure , physics , thermodynamics
By 1 week post‐myocardial infarction (MI), MMP‐28 null mice show exacerbated cardiac rupture and dysfunction associated with inhibition of M2 macrophage activation, extracellular matrix deposition, and collagen cross‐linking. The impact of MMP‐28 deletion on the early inflammatory response, however, remains to be evaluated. C57BL/6J wild type (WT, n=12) and MMP‐28 null (n=12) mice at 3–6 months of age were subjected to permanent coronary artery ligation and sacrificed at 1 day (d). Ejection fraction declined from 62 ±1% at baseline to 17±1% at d1 in WT (p<0.05), and this decline was attenuated 24% by MMP‐28 deletion (p<0.05). In the infarct region, 21 out of 84 inflammatory genes increased and 16 decreased in WT, while 21 were elevated and 11 reduced in MMP‐28 null mice, compared to corresponding d0 values (all p<0.05). Ccl22, Ccr8, Cxcr5, Il13, Il1α, Il1f6, and Ltb were lower in MMP‐28 null (all p<0.05), suggesting reduced recruitment or activation of neutrophils. By immunohistochemistry, 28% fewer neutrophil infiltration was noted in MMP‐28 null. In conclusion, MMP‐28 deletion attenuated d1 cardiac function by inhibiting neutrophil infiltration to limit the early inflammatory response.