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Am J Physiol Heart Circ Physiol (December 23, 2003). doi:10.1152/ajpheart.00479.2002
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Submitted on June 7, 2002
Accepted on December 19, 2003

Elafin Overexpressing Mice Have Improved Cardiac Function After Myocardial Infarction

Kunio Ohta1, Takanori Nakajima1, Alexander Y.L. Cheah1, Syed H.E. Zaidi1, Nilo Kaviani1, Fayez Dawood2, Xiao-Mang You2, Peter Liu2, Mansoor Husain2, and Marlene Rabinovitch3*

1 Program in Cardiovascular Research, and The Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada
2 Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, The Toronto Hospital Network, Toronto, ON, Canada
3 Program in Cardiovascular Research, and The Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

* To whom correspondence should be addressed. E-mail: marlener{at}stanford.edu.

Elevated serine elastase activity following 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 non-transgenic littermates as early as 6h after LAD ligation and persisted at 4d and 7d, but not in sham operated or elafin overexpressing transgenic mice. Myeloperoxidase activity (index of inflammatory cells) and matrix metalloproteinase 2 (MMP2) were also increased but only at 4d and 7d and only in nontransgenic mice (P<0.05 for both comparisons), and this increase correlated with inflammatory cell infiltration. Echocardiographic study at 4d revealed indices of diastolic dysfunction in nontransgenic vs. elafin overexpressing mice (P<0.05). Morphometric and biochemical analyses at 28d indicated impairment in cardiac performance, with greater scar thinning and infarct expansion in non-transgenic vs. elafin transgenic littermates (p<0.05 for all comparisons). Thus, serine elastase inhibition appears to suppress inflammation, cardiac dilatation and dysfunction after myocardial infarct.




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