Inhibition of myocardial cathepsin-L release during reperfusion following myocardial infarction improves cardiac function and reduces infarct size.

Autor:	He W; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., McCarroll CS; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Nather K; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Ford K; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Mangion K; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Riddell A; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., O'Toole D; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Zaeri A; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Corcoran D; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Carrick D; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Lee MMY; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., McEntegart M; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Davie A; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Good R; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Lindsay MM; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Eteiba H; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Rocchiccioli P; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Watkins S; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Hood S; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Shaukat A; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., McArthur L; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Elliott EB; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., McClure J; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Hawksby C; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Martin T; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Petrie MC; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Oldroyd KG; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Smith GL; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Channon KM; Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, UK., Berry C; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.; West of Scotland Heart and Lung Centre, Golden Jubilee National Hospital, Clydebank G81 4DY, UK., Nicklin SA; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK., Loughrey CM; Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, Glasgow Cardiovascular Research Centre, University of Glasgow, University Place, Glasgow G12 8TA, UK.
Jazyk:	angličtina
Zdroj:	Cardiovascular research [Cardiovasc Res] 2022 May 06; Vol. 118 (6), pp. 1535-1547.
DOI:	10.1093/cvr/cvab204
Abstrakt:	Aims: Identifying novel mediators of lethal myocardial reperfusion injury that can be targeted during primary percutaneous coronary intervention (PPCI) is key to limiting the progression of patients with ST-elevation myocardial infarction (STEMI) to heart failure. Here, we show through parallel clinical and integrative preclinical studies the significance of the protease cathepsin-L on cardiac function during reperfusion injury. 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. (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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