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Matrix Metalloproteinase‐28 Deletion Attenuates Short‐term Left Ventricular Dysfunction but Exacerbates Cardiac Rupture Post‐Myocardial Infarction in Mice
Author(s) -
Ma Yonggang,
Zhang Jianhua,
Ramirez Trevi A.,
Manicone Anne M.,
Lindsey Merry L.
Publication year - 2012
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.26.1_supplement.1060.1
Subject(s) - myocardial infarction , medicine , ejection fraction , cardiac rupture , cardiology , ligation , matrix metalloproteinase , left coronary artery , cardiac function curve , ventricular remodeling , chemokine , heart rupture , heart failure , endocrinology , inflammation
Matrix metalloproteinase (MMP)‐28 is expressed in normal adult hearts and is also expressed in macrophages suggesting a role in cardiac wound healing. The significance of MMP‐28 in myocardial infarction (MI), however, has not been explored. Adult C57BL/6 wild type (WT) and MMP‐28 −/− mice were subjected to left coronary artery ligation and sacrificed at multiple time points up to day 7 post‐MI. Immunofluorescence showed that MMP‐28 was expressed by cardiomyocytes under normal conditions and by macrophages post‐MI. Ejection fraction at day 1 post‐MI was markedly depressed in WT (17±2%), and this impaired function was attenuated in the MMP‐28 −/− mice (23±1%; p<0.05, n=9/group). The 7 day survival rate after MI for WT was 59% (13/22) and for MMP‐28 −/− was 30% (10/33; p<0.05). Autopsy data revealed that 33% of WT mice died from left ventricular (LV) rupture; however, the rupture rate in MMP‐28 −/− mice was 87% (p<0.05). At day 5 post‐MI, the mRNA levels of 14 out of 84 inflammatory genes were statistically increased in the infarct regions of the MMP‐28 −/− mice, compared to WT (all p<0.05). Included genes were Casp1, Ccl2, Ccl7, Ccl12, Ccr5, Ccr7, Ccr9, Cxcr3, Cxcr5, Il2rg, Il10ra, Ltb, Tgfb1 and Tnfrsf1b. In conclusion, MMP‐28 deletion blunts short‐term LV dysfunction, but aggravates cardiac rupture by exacerbating the pro‐inflammatory response.