Inhibition of myocardial cathepsin-L release during reperfusion following myocardial infarction improves cardiac function and reduces infarct size.
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He Weihong, McCarroll Charlotte S, Nather Katrin, Ford Kristopher, Mangion Kenneth, Riddell Alexandra, O'Toole Dylan, Zaeri Ali, Corcoran David, Carrick David, Lee Mathew M Y, McEntegart Margaret, Davie Andrew, Good Richard, Lindsay Mitchell M, Eteiba Hany, Rocchiccioli Paul, Watkins Stuart, Hood Stuart, Shaukat Aadil, McArthur Lisa, Elliott Elspeth B, McClure John, Hawksby Catherine, Martin Tamara, Petrie Mark C, Oldroyd Keith G, Smith Godfrey L, Oxford Acute Myocardial Infarction (OxAMI) Study, Channon Keith M, Berry Colin, Nicklin Stuart A, Loughrey Christopher M
Аннотация
METHODS AND RESULTS: We found that direct cardiac release of cathepsin-L in STEMI patients (n = 76) immediately post-PPCI leads to elevated serum cathepsin-L levels and that serum levels of cathepsin-L in the first 24 h post-reperfusion are associated with reduced cardiac contractile function and increased infarct size. Preclinical studies demonstrate that inhibition of cathepsin-L release following reperfusion injury with CAA0225 reduces infarct size and improves cardiac contractile function by limiting abnormal cardiomyocyte calcium handling and apoptosis.
CONCLUSION: Our findings suggest that cathepsin-L is a novel therapeutic target that could be exploited clinically to counteract the deleterious effects of acute reperfusion injury after an acute STEMI.