Post-Ischemic Treatment of Recombinant Human Secretory Leukocyte Protease Inhibitor (rhSLPI) Reduced Myocardial Ischemia/Reperfusion Injury.

Podsawee Mongkolpathumrat,Aussara Panya,Anusak Kijtawornrat,Sarawut Kumphune,Eakkapote Prompunt,Stephanie Barrère-Lemaire,Nipon Chattipakorn

doi:10.3390/biomedicines9040422

Abstract

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.

Highlights

Impaired blood supply in cardiac tissue due to coronary occlusion, during acute myocardial infarction (AMI), leads to cardiac tissue injury or death, which subsequently causes cardiac dysfunction and mortality
The animal body weight was measured before the surgery and heart weight was The animal body weight was measured before the surgery and heart weight was measured after the end of surgical procedures
The results show that the body weight of measured after the end of surgical procedures

Summary

Introduction

Impaired blood supply in cardiac tissue due to coronary occlusion, during acute myocardial infarction (AMI), leads to cardiac tissue injury or death, which subsequently causes cardiac dysfunction and mortality. The most effective therapeutic intervention for limiting the aggravation of tissue injury and death is to restore blood flow 4.0/). Biomedicines 2021, 9, 422 using reperfusion therapy. This could be performed by thrombolytic treatment or percutaneous coronary intervention (PCI) [1]. Any post-ischemic interventions or treatments that prevent the detrimental activation of reperfusion injury are likely to decrease infarct size, save patients’ lives and improve their quality of life

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Conclusion