Abstract
Background: Echinatin (Ech) has been reported to exert antioxidant and anti-inflammatory activities. In this study, we aimed to characterize the functional role of Ech in myocardial ischemic/reperfusion (MI/R) injury and elucidate its underlying mechanism of action. Method: We established in vivo and in vitro models of MI/R injury to determine the effect of Ech on MI/R injury. Gene expression was examined using quantitative real-time polymerase chain reaction and western blotting. Myocardial infarction was assessed using tetrazolium chloride staining and the degree of myocardial injury was evaluated by measuring lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB) levels. Cell apoptosis was detected using the terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) assay. The viability of H9c2 cells was determined using Cell Counting Kit-8 assay. Results: MI/R induced myocardial infarction, which was mitigated by Ech treatment. Moreover, Ech treatment resulted in a marked decline of LDH and CK-MB levels in the serum and myocardium of MI/R rats. Ech treatment also restrained cardiomyocyte apoptosis in vivo and in vitro, as evidenced by reduction in LDH release, the number of TUNEL-positive cells, and caspase-3 activity. Furthermore, Ech administration inhibited MI/R-induced activation of Hippo/Yes-associated protein signaling in vivo and in vitro, as indicated by inhibition of mammalian sterile 20-like protein kinase 1, large tumor suppressor one, and YAP phosphorylation and promotion of YAP nuclear translocation. However, silencing of YAP counteracted the protective effect of Ech on hypoxia/reoxygenation-induced myocardial injury in vitro. Conclusion: Ech exerted its protective effect against MI/R injury at least partially by suppressing the Hippo/YAP signaling pathway, providing novel insights into the remission of MI/R injury.
Highlights
Myocardial infarction, resulting from the interruption of blood supply, is one of the most frequent cardiovascular emergencies, which remains to be the major cause of mortality and disability worldwide (Thygesen et al, 2018)
Ech exerted its protective effect against myocardial ischemic/reperfusion (MI/R) injury at least partially by suppressing the Hippo/YAP signaling pathway, providing novel insights into the remission of MI/R injury
MI/R rats showed a significant increase in the levels of serum lactate dehydrogenase (LDH) and creatine kinase-myocardial band (CK-MB) relative to the sham group; Ech treatment attenuated MI/R-induced elevation of LDH and CK-MB serum levels (Figures 1B,C)
Summary
Myocardial infarction, resulting from the interruption of blood supply, is one of the most frequent cardiovascular emergencies, which remains to be the major cause of mortality and disability worldwide (Thygesen et al, 2018). Restoration of blood flow in the infarcted coronary artery as soon as possible is considered as the most effective treatment for myocardial infarction (Anderson and Morrow, 2017). Restoration of coronary circulation may aggravate reversible myocardial ischemia injury and lead to irreversible myocardial injury, termed as myocardial ischemic/reperfusion (MI/R) injury (Ferrari et al, 2017). MI/R injury is associated with poor clinical outcomes in patients with myocardial infarction and causes multiple cardiac complications. We aimed to characterize the functional role of Ech in myocardial ischemic/reperfusion (MI/R) injury and elucidate its underlying mechanism of action
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