Elafin-overexpressing mice have improved cardiac function after myocardial infarction.
Elevated serine elastase activity after myocardial infarction can contribute to remodeling associated with left ventricular dilatation and dysfunction. We therefore assessed the effects of overexpressing the selective serine elastase inhibitor elafin in transgenic mice in which a myocardial infarction was caused by ligation of the left anterior descending coronary artery (LAD). Elevated serine elastase activity was observed in nontransgenic littermates as early as 6 h after LAD ligation and persisted at 4 and 7 days but not in sham-operated or elafin-overexpressing transgenic mice. Myeloperoxidase activity (index of inflammatory cells) and matrix metalloproteinase 2 were also increased but only at 4 and 7 days and only in nontransgenic mice (P < 0.05 for both comparisons), and this increase correlated with inflammatory cell infiltration. Echocardiographic study at 4 days revealed indexes of diastolic dysfunction in nontransgenic versus elafin-overexpressing mice (P < 0.05). Morphometric and biochemical analyses at 28 days indicated impairment in cardiac performance, with greater scar thinning and infarct expansion in nontransgenic versus elafin transgenic littermates (P < 0.05 for all comparisons). Thus serine elastase inhibition appears to suppress inflammation, cardiac dilatation, and dysfunction after myocardial infarct.
Ohta
Kunio
K
Program in Cardiovascular Research, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Canada.
Nakajima
Takanori
T
Cheah
Alexander Y L
AY
Zaidi
Syed H E
SH
Kaviani
Nilo
N
Dawood
Fayez
F
You
Xiao-Mang
XM
Liu
Peter
P
Husain
Mansoor
M
Rabinovitch
Marlene
M
D000818:Animals; D002921:Cicatrix / Q000473:pathology; D004452:Echocardiography; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism*
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D009195:Peroxidase; D010196:Pancreatic Elastase; D020778:Matrix Metalloproteinase 2