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

Prompunt, Eakkapote; Sanit, Jantira; Barrère-Lemaire, Stéphanie; Nargeot, Joël; Noordali, Hannah; Madhani, Melanie; Kumphune, Sarawut

doi:10.3892/etm.2018.6097

Cited by 23 publications

(32 citation statements)

References 57 publications

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“…p38 pathway activation by MKK6 overexpression results in interstitial and perivascular cardiac fibrosis [ 74 ], and p38 inhibition may underlie the beneficial effects of some statins on cardiac remodeling after myocardial infarction [ 75 , 76 ]. Supporting this idea, protease inhibitors induce cardioprotection in models of ischemia–reperfusion, in part by attenuating p38 phosphorylation, leading to reductions in injury, ROS levels, and infarct size [ 77 ].…”

Section: P38 In Ischemia–reperfusion Injurymentioning

confidence: 99%

p38 MAPK Pathway in the Heart: New Insights in Health and Disease

Romero-Becerra

Santamans

Folgueira

et al. 2020

IJMS

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The p38 mitogen-activated kinase (MAPK) family controls cell adaptation to stress stimuli. p38 function has been studied in depth in relation to cardiac development and function. The first isoform demonstrated to play an important role in cardiac development was p38α; however, all p38 family members are now known to collaborate in different aspects of cardiomyocyte differentiation and growth. p38 family members have been proposed to have protective and deleterious actions in the stressed myocardium, with the outcome of their action in part dependent on the model system under study and the identity of the activated p38 family member. Most studies to date have been performed with inhibitors that are not isoform-specific, and, consequently, knowledge remains very limited about how the different p38s control cardiac physiology and respond to cardiac stress. In this review, we summarize the current understanding of the role of the p38 pathway in cardiac physiology and discuss recent advances in the field.

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Section: P38 In Ischemia–reperfusion Injurymentioning

confidence: 99%

p38 MAPK Pathway in the Heart: New Insights in Health and Disease

Romero-Becerra

Santamans

Folgueira

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…Restoring blood flow to the ischemic myocardium is the most effective treatment to rescue ischemic myocardium cells and to save the life of the patient (6). However, this treatment can cause an abrupt restoration of the oxygen supply and the reperfusion of myocardium may aggravate myocardial injury, leading to a reperfusion injury (7,8). Therefore, it is necessary to explore and to better understand the potential molecular mechanism of myocardial I/R injury.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑138 attenuates myocardial ischemia reperfusion injury through inhibiting mitochondria‑mediated apoptosis by targeting HIF1‑α

et al. 2019

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Myocardial ischemia-reperfusion (I/R) injury is considered to have a detrimental role in coronary heart disease, which is considered to be the leading cause of death worldwide. However, the molecular mechanism involved in the progression of myocardial I/R injury is still unclear. The current study aimed to investigate the expression and function of microRNA (miR)-138 in the process of myocardial I/R injury. First, miR-138 expression levels were analyzed both in myocardium with I/R injury and control myocardium using reverse transcription-quantitative polymerase chain reaction analysis. Then, the relationship between the levels of miR-138 and hypoxia-inducible factor (HIF)1-α was also investigated using a luciferase reporter assay. Assessment of myocardial infarct size, measurements of serum myocardial enzymes and electron microscopy analysis were all utilized to analyse the effect of miR-138 on myocardial I/R injury. The authors of current study also used western blotting to examine the expression levels of the mitochondrial fission-related proteins dynamin-1-like protein and mitochondrial fission 1 protein. It was found that miR-138 is downregulated and HIF1-α is upregulated after myocardial ischemia reperfusion injury. Overexpression of miR-138 reduced myocardial I/R injury-induced infarct sizes and myocardial enzyme levels, and it also inhibited the expression of proteins related to mitochondrial morphology and myocardial I/R-induced mitochondrial apoptosis by targeting HIF1-α. Taken together, these findings provide a novel insight into the molecular mechanism of miR-138 and HIF1-α in the progression of myocardial I/R injury. miR-138 has the potential to become a promising therapeutic target for treating myocardial I/R injury.

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“…SLPI can also compete with NF-κB (p65) for binding to the DNA consensus binding site in the promotor region of NF-κB-regulated genes (23–25, 29, 30). Furthermore, stimulation with SLPI was shown to attenuate p38 MAPK activation and increase Akt phosphorylation in rat adult ventricular myocytes (31). SLPI-deficient mice exhibit normal fetal development, survive into adulthood and show no obvious pathological phenotype (32).…”

Section: Introductionmentioning

confidence: 99%

SLPI Inhibits ATP-Mediated Maturation of IL-1β in Human Monocytic Leukocytes: A Novel Function of an Old Player

et al. 2019

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Interleukin-1β (IL-1β) is a potent, pro-inflammatory cytokine of the innate immune system that plays an essential role in host defense against infection. However, elevated circulating levels of IL-1β can cause life-threatening systemic inflammation. Hence, mechanisms controlling IL-1β maturation and release are of outstanding clinical interest. Secretory leukocyte protease inhibitor (SLPI), in addition to its well-described anti-protease function, controls the expression of several pro-inflammatory cytokines on the transcriptional level. In the present study, we tested the potential involvement of SLPI in the control of ATP-induced, inflammasome-dependent IL-1β maturation and release. We demonstrated that SLPI dose-dependently inhibits the ATP-mediated inflammasome activation and IL-1β release in human monocytic cells, without affecting the induction of pro-IL-1β mRNA by LPS. In contrast, the ATP-independent IL-1β release induced by the pore forming bacterial toxin nigericin is not impaired, and SLPI does not directly modulate the ion channel function of the human P2X 7 receptor heterologously expressed in Xenopus laevis oocytes. In human monocytic U937 cells, however, SLPI efficiently inhibits ATP-induced ion-currents. Using specific inhibitors and siRNA, we demonstrate that SLPI activates the calcium-independent phospholipase A2β (iPLA2β) and leads to the release of a low molecular mass factor that mediates the inhibition of IL-1β release. Signaling involves nicotinic acetylcholine receptor subunits α7, α9, α10, and Src kinase activation and results in an inhibition of ATP-induced caspase-1 activation. In conclusion, we propose a novel anti-inflammatory mechanism induced by SLPI, which inhibits the ATP-dependent maturation and secretion of IL-1β. This novel signaling pathway might lead to development of therapies that are urgently needed for the prevention and treatment of systemic inflammation.

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

Cited by 23 publications

References 57 publications

p38 MAPK Pathway in the Heart: New Insights in Health and Disease

p38 MAPK Pathway in the Heart: New Insights in Health and Disease

MicroRNA‑138 attenuates myocardial ischemia reperfusion injury through inhibiting mitochondria‑mediated apoptosis by targeting HIF1‑α

SLPI Inhibits ATP-Mediated Maturation of IL-1β in Human Monocytic Leukocytes: A Novel Function of an Old Player

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