A disintegrin and metalloproteinase 17 (ADAM17), also known as tumor necrosis factor (TNF)-α-converting enzyme, is a ubiquitously expressed membrane-bound sheddase that cleaves many membrane-bound molecules, including cytokines, growth factors, and receptors to activate or inactivate various cellular signaling pathways. 1-3 ADAM17 is expressed in multiple organs and cell types, including the cardiomyocytes in the heart. 1,4 ADAM17 levels are elevated in the heart of patients with myocarditis, 4

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... dilated cardiomyopathy, and hypertrophic obstructive cardiomyopathy, 5 whereas its levels in serum are elevated in acute myocardial infarction (MI) [6][7][8][9] and advanced congestive heart failure. 10 Elevated ADAM17 levels correlate negatively with left ventricular systolic function and post-MI outcomes. 4,6-10 However, it is not known whether the elevated ADAM17 contributes to disease progression or is a compensatory response to counteract disease pathogenesis. 5] [16] [17] [18] We used cardiomyocyte-specific ADAM17 knockdown mice to examine the role of cardiac ADAM17 in post-MI myocardial repair. Clinical Perspective on p 979 Methods Detailed Methods are available in the Data Supplement.