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The role of Caspase 1 in ischemia/reperfusion injury of the myocardium

Rauf, A; Shah, M; Yellon, DM; Davidson, SM; (2019) The role of Caspase 1 in ischemia/reperfusion injury of the myocardium. Journal of Cardiovascular Pharmacology 10.1097/FJC.0000000000000694. (In press).

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Abstract

Acute occlusion of a coronary artery can result in myocardial infarction - a leading cause of premature death. Prompt restoration of blood flow to the myocardium can prevent excessive death of cardiomyocytes and improve clinical outcome. Although the major mechanism of cell death after reperfusion is necrosis, it is now recognized that many other cell death pathways may be involved in ischemia-reperfusion (I/R) injury. Pyroptosis is one such cell death pathway that is caspase-1-dependent and induced in response to cellular insult. The activated caspase-1 protease cleaves and activates specific cellular targets including gasdermin D and the pro-inflammatory cytokines interleukin-1β and interleukin-18. The N-terminal fragment of gasdermin D forms plasma membrane pores resulting in cytosolic leakage and cell rupture, releasing interleukin-1beta and interleukin-18. Evidence suggests that inflammation induced by I/R via the pyroptotic pathway contributes to cardiomyocyte death, excessive scar formation and poor ventricular remodeling. For this reason, there is growing interest in targeting components of the pyroptotic pathway as a means of reducing I/R injury.

Type: Article
Title: The role of Caspase 1 in ischemia/reperfusion injury of the myocardium
Location: United States
DOI: 10.1097/FJC.0000000000000694
Publisher version: https://doi.org/10.1097/FJC.0000000000000694
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: https://discovery.ucl.ac.uk/id/eprint/10080146
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