Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury
Myocardial ischemia/reperfusion (I/R) injury is a major cause of mortality and morbidity worldwide. Among factors contributing to I/R injury, proteolytic enzymes could also cause cellular injury, expand the injured area and induce inflammation, which then lead to cardiac dysfunction. Therefore, prot...
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MDPI AG
2021-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/4/422 |
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| author | Podsawee Mongkolpathumrat Anusak Kijtawornrat Eakkapote Prompunt Aussara Panya Nipon Chattipakorn Stephanie Barrère-Lemaire Sarawut Kumphune |
| author_facet | Podsawee Mongkolpathumrat Anusak Kijtawornrat Eakkapote Prompunt Aussara Panya Nipon Chattipakorn Stephanie Barrère-Lemaire Sarawut Kumphune |
| author_sort | Podsawee Mongkolpathumrat |
| collection | DOAJ |
| description | Myocardial ischemia/reperfusion (I/R) injury is a major cause of mortality and morbidity worldwide. Among factors contributing to I/R injury, proteolytic enzymes could also cause cellular injury, expand the injured area and induce inflammation, which then lead to cardiac dysfunction. Therefore, protease inhibition seems to provide therapeutic benefits. Previous studies showed the cardioprotective effect of secretory leukocyte protease inhibitor (SLPI) against myocardial I/R injury. However, the effect of a post-ischemic treatment with SLPI in an in vivo I/R model has never been investigated. In the present study, recombinant human (rh) SLPI (rhSLPI) was systemically injected during coronary artery occlusion or at the onset of reperfusion. The results show that post-ischemic treatment with rhSLPI could significantly reduce infarct size, Lactate Dehydrogenase (LDH) and Creatine kinase-MB (CK-MB) activity, inflammatory cytokines and protein carbonyl levels, as well as improving cardiac function. The cardioprotective effect of rhSLPI is associated with the attenuation of p38 MAPK phosphorylation, Bax, caspase-3 and -8 protein levels and enhancement of pro-survival kinase Akt and ERK1/2 phosphorylation. In summary, this is the first report showing the cardioprotective effects against myocardial I/R injury of post-ischemic treatments with rhSLPI in vivo. Thus, these results suggest that SLPI could be used as a novel therapeutic strategy to reduce myocardial I/R injury. |
| first_indexed | 2024-03-10T12:21:36Z |
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| institution | Directory Open Access Journal |
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| last_indexed | 2024-03-10T12:21:36Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
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| series | Biomedicines |
| spelling | doaj.art-cbc331ce6fab4766abaebf56161e181b2023-11-21T15:27:27ZengMDPI AGBiomedicines2227-90592021-04-019442210.3390/biomedicines9040422Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion InjuryPodsawee Mongkolpathumrat0Anusak Kijtawornrat1Eakkapote Prompunt2Aussara Panya3Nipon Chattipakorn4Stephanie Barrère-Lemaire5Sarawut Kumphune6Graduate Programs in Biomedical Sciences, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, ThailandDepartment of Physiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, ThailandUnit of Excellence in Infectious Disease, Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, ThailandDepartment of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200, ThailandCardiac Electrophysiology Research and Training Centre, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandInstitut de Génomique Fonctionnelle, Université de Montpellier, CNRS, Inserm, 141, rue de la Cardonille, 34094 Montpellier, FranceGraduate Programs in Biomedical Sciences, Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, ThailandMyocardial ischemia/reperfusion (I/R) injury is a major cause of mortality and morbidity worldwide. Among factors contributing to I/R injury, proteolytic enzymes could also cause cellular injury, expand the injured area and induce inflammation, which then lead to cardiac dysfunction. Therefore, protease inhibition seems to provide therapeutic benefits. Previous studies showed the cardioprotective effect of secretory leukocyte protease inhibitor (SLPI) against myocardial I/R injury. However, the effect of a post-ischemic treatment with SLPI in an in vivo I/R model has never been investigated. In the present study, recombinant human (rh) SLPI (rhSLPI) was systemically injected during coronary artery occlusion or at the onset of reperfusion. The results show that post-ischemic treatment with rhSLPI could significantly reduce infarct size, Lactate Dehydrogenase (LDH) and Creatine kinase-MB (CK-MB) activity, inflammatory cytokines and protein carbonyl levels, as well as improving cardiac function. The cardioprotective effect of rhSLPI is associated with the attenuation of p38 MAPK phosphorylation, Bax, caspase-3 and -8 protein levels and enhancement of pro-survival kinase Akt and ERK1/2 phosphorylation. In summary, this is the first report showing the cardioprotective effects against myocardial I/R injury of post-ischemic treatments with rhSLPI in vivo. Thus, these results suggest that SLPI could be used as a novel therapeutic strategy to reduce myocardial I/R injury.https://www.mdpi.com/2227-9059/9/4/422ischemic heart diseaseischemia/reperfusion injurysecretory leukocyte protease inhibitor (SLPI)cardioprotectionpost-ischemic treatment |
| spellingShingle | Podsawee Mongkolpathumrat Anusak Kijtawornrat Eakkapote Prompunt Aussara Panya Nipon Chattipakorn Stephanie Barrère-Lemaire Sarawut Kumphune Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury Biomedicines ischemic heart disease ischemia/reperfusion injury secretory leukocyte protease inhibitor (SLPI) cardioprotection post-ischemic treatment |
| title | Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury |
| title_full | Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury |
| title_fullStr | Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury |
| title_full_unstemmed | Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury |
| title_short | Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury |
| title_sort | post ischemic treatment of recombinant human secretory leukocyte protease inhibitor rhslpi reduced myocardial ischemia reperfusion injury |
| topic | ischemic heart disease ischemia/reperfusion injury secretory leukocyte protease inhibitor (SLPI) cardioprotection post-ischemic treatment |
| url | https://www.mdpi.com/2227-9059/9/4/422 |
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