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

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.

Effect of Cerium Oxide Nanoparticles on Myocardial Cell Apoptosis Induced by Myocardial Ischemia-Reperfusion Injury

“…The number of deaths caused by cardiovascular diseases (CVDs) accounts for a large part of the total deaths in the world, and CVDs will be regarded as the most important cause of human life safety with the improvement of people's living standards (1,2). A large number of ischemic heart diseases cause insufficiency of blood supply to the heart in patients, leading to adverse events such as myocardial infarction and sudden death (3). Fast and effective restoration of blood supply in patients has become the key to the treatment of ischemic heart disease.…”

Murine neonatal cardiac B cells promote cardiomyocyte proliferation and heart regeneration

“…We further re-analyzed single-cell RNA sequencing (scRNA-Seq) data of adult mouse heart tissues after MI or sham operation presented in previous research (GSE163465) 8 . Several genes encoded secreted proteins that had been reported to promote cell proliferation were significantly upregulated in B cells from cardiac tissues of adult mice post-MI, which included secretory leukocyte peptidase inhibitor ( Slpi ) 9 , immunoglobulin heavy constant gamma 1 ( Ighg1 ) 10 , lipocalin 2 ( Lcn2 ) 11 , s100 calcium-binding protein A8 ( S100a8 ) 12 , s100 calcium-binding protein A9 ( S100a9 ) 13 and C-X-C motif chemokine ligand 2 ( Cxcl2 ) 14 (Fig. 2b ).…”