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Open AccessArticle

Endothelial-Cell-Derived Human Secretory Leukocyte Protease Inhibitor (SLPI) Protects Cardiomyocytes against Ischemia/Reperfusion Injury

1
Biomedical Research Unit in Cardiovascular Sciences (BRUCS), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
2
Graduate Program in Biomedical Sciences, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
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Department of Cardio-Thoracic Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
4
Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, Thailand
5
Department of Medical Technology, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 678; https://doi.org/10.3390/biom9110678
Received: 26 September 2019 / Revised: 30 October 2019 / Accepted: 30 October 2019 / Published: 31 October 2019
(This article belongs to the Section Biological Factors)
Vascular endothelial cell (EC)-derived factors play an important role in endothelial–cardiomyocyte crosstalk and could save cardiomyocytes (CMs) from injury. The manipulation of endothelial cells to secrete protective factors could enhance cardioprotection. Secretory leukocyte protease inhibitor (SLPI) has been known to protect the heart. The goal of this study was to evaluate the in vitro paracrine protective effect and mechanisms of EC-derived human SLPI on cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Stable endothelial cells overexpressing human SLPI were generated from an endothelial cell line (EA.hy926). The cytoprotective effect was determined by cell survival assay. The results showed that endothelial-derived recombinant human SLPI (rhSLPI) reduced simulated ischemia/reperfusion (I/R)-(81.75% ± 1.42% vs. 60.27% ± 2.52%, p < 0.05) and hypoxia/reoxygenation (H/R)-induced EC injury (83.57% ± 1.78% vs. 63.07% ± 1.93%, p < 0.05). Moreover, co-culture of ECs overexpressing rhSLPI with CMs at ratios 1:1 and 1:3 or treatment with conditioned medium enhanced cell viability by 10.51–16.7% (co-culture) and 15.25–20.45% (conditioned medium) by reducing intracellular reactive oxygen species (ROS) production, the Bax/Bcl-2 expression ratio, caspase-3, and caspase-8, and in preconditioned CMs by activation of p38 MAPK and Akt survival kinase. In conclusion, this study showed for the first time that EC-derived rhSLPI provided cardio-vasculoprotective effects against I/R injury as a possible alternative therapeutic strategy for cardioprotection. View Full-Text
Keywords: ischemia/reperfusion injury; anti-protease; secretory leukocyte protease inhibitor; protease inhibitor; cardioprotection; endothelial cells; cardiomyocytes ischemia/reperfusion injury; anti-protease; secretory leukocyte protease inhibitor; protease inhibitor; cardioprotection; endothelial cells; cardiomyocytes
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Kongpol, K.; Nernpermpisooth, N.; Prompunt, E.; Kumphune, S. Endothelial-Cell-Derived Human Secretory Leukocyte Protease Inhibitor (SLPI) Protects Cardiomyocytes against Ischemia/Reperfusion Injury. Biomolecules 2019, 9, 678.

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