The cardioprotective effects of secretory leukocyte protease inhibitor against myocardial ischemia/reperfusion injury

Prompunt,Eakkapote; Sanit,Jantira; Barrère‑Lemaire,Stephanie; Nargeot,Joel; Noordali,Hannah; Madhani,Melanie; Kumphune,Sarawut

doi:10.3892/etm.2018.6097

The cardioprotective effects of secretory leukocyte protease inhibitor against myocardial ischemia/reperfusion injury

Authors:
- Eakkapote Prompunt
- Jantira Sanit
- Stephanie Barrère‑Lemaire
- Joel Nargeot
- Hannah Noordali
- Melanie Madhani
- Sarawut Kumphune
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Affiliations: Biomedical Research Unit in Cardiovascular Sciences, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand, Department of Physiology, Institute of Functional Genomics, National Centre for Scientific Research, French National Institute of Health and Medical Research, University of Montpellier, 34090 Montpellier, France, Institute of Cardiovascular Sciences, School of Medical and Dental Sciences, University of Birmingham, B15 2TT Birmingham, UK
Published online on: April 25, 2018 https://doi.org/10.3892/etm.2018.6097
Pages: 5231-5242
Copyright: © Prompunt et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Protease enzymes generated from injured cells and leukocytes are the primary cause of myocardial cell damage following ischemia/reperfusion (I/R). The inhibition of protease enzyme activity via the administration of particular drugs may reduce injury and potentially save patients' lives. The aim of the current study was to investigate the cardioprotective effects of treatment with recombinant human secretory leukocyte protease inhibitor (rhSLPI) on in vitro and ex vivo models of myocardial I/R injury. rhSLPI was applied to isolated adult rat ventricular myocytes (ARVMs) subjected to simulated I/R and to ex vivo murine hearts prior to I/R injury. Cellular injury, cell viability, reactive oxygen species (ROS) levels, and levels of associated proteins were assessed. The results demonstrated that administration of rhSLPI prior to or during sI/R significantly reduced the death and injury of ARVMs and significantly reduced intracellular ROS levels in ARVMs during H2O2 stimulation. In addition, treatment of ARVMs with rhSLPI significantly attenuated p38 mitogen‑activated protein kinase (MAPK) activation and increased the activation of Akt. Furthermore, pretreatment of ex vivo murine hearts with rhSLPI prior to I/R significantly decreased infarct size, attenuated p38 MAPK activation and increased Akt phosphorylation. The results of the current study demonstrated that treatment with rhSLPI induced a cardioprotective effect and reduced ARVM injury and death, intracellular ROS levels and infarct size. rhSLPI also attenuated p38 MAPK phosphorylation and activated Akt phosphorylation. These results suggest that rhSLPI may be developed as a novel therapeutic strategy of treating ischemic heart disease.

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