Erythropoietin protects myocardium against ischemia–reperfusion injury under moderate hyperglycemia

Jun, Ji Hae; Jun, Na Hyung; Shim, Jæ Kwang; Shin, Eun Jung; Kwak, Young Lan

doi:10.1016/j.ejphar.2014.09.038

Cited by 22 publications

(17 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pretreatment of the rats with 5,000 U/kg EPO was shown to significantly attenuate the pathological changes associated with myocardial IRI. In agreement with the current results, pre vious studies have suggested that treatment of rats with EPO significantly decreases the pathological injury to the heart tissue that is induced by myocardial IRI (12,17,18). The present data indicate that EPO may be a novel agent for the prevention of myocardial IRI in clinical practice.…”

Section: Discussionsupporting

confidence: 92%

Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

Ren

Xiao

2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Erythropoietin (EPO), a glycoprotein originally known for its important role in the stimulation of erythropoiesis, has recently been shown to have significant protective effects in animal models of kidney and intestinal ischemia-reperfusion injury (IRI). However, the mechanism underlying these protective effects remains unclear. The aim of the current study was to evaluate the effects of EPO on myocardial IRI and to investigate the mechanism underlying these effects. A total of 18 male Sprague Dawley rats were randomly divided into three groups, namely the sham, IRI-saline and IRI-EPO groups. Rats in the IRI-EPO group were administered 5,000 U/kg EPO intraperitoneally 24 h prior to the induction of IRI. IRI was induced by ligating the left descending coronary artery for 30 min, followed by reperfusion for 3 h. Pathological changes in the myocardial tissue were observed and scored. The levels of the proinflammatory cytokines, interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α, were evaluated in the serum and myocardial tissue. Furthermore, the effects of EPO on phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling and EPO receptor (EPOR) phosphorylation were measured. Pathological changes in the myocardial tissue, increased expression levels of TNF-α, IL-6 and IL-1β in the myocardium, and increased serum levels of these mediators, as a result of IRI, were significantly decreased by EPO pretreatment. The effects of EPO were found to be associated with the activation of PI3K/Akt signaling, which suppressed the inflammatory responses, following the initiation of EPOR activation by EPO. Therefore, EPO pretreatment was demonstrated to decrease myocardial IRI, which was associated with activation of EPOR, subsequently increasing PI3K/Akt signaling to inhibit the production and release of inflammatory mediators. Thus, the results of the present study indicated that EPO may be useful for preventing myocardial IRI.

show abstract

Section: Discussionsupporting

confidence: 92%

Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

Ren

Xiao

2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…MAPK compounds, including ERK, stress-activated protein kinases/c-Jun NH 2 -terminal kinases and p38 MAPKs have been implicated in inflammatory signaling mechanisms in I/R injury (30,31). Additionally, ERK signaling serves a crucial function in I/R-induced cell apoptosis (32,33).…”

Section: Discussionmentioning

confidence: 99%

Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling

Zhu

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Gynostemma pentaphyllum is a traditional Chinese medicine reported to possess a wide range of health benefits. As the major component of G. pentaphyllum, gypenoside (GP) displays various anti-inflammatory and anti-oxidant properties. However, it is unclear whether GP can protect against ischemia/reperfusion (I/R)-induced renal injury, and the underlying molecular mechanisms associated with this process remain unknown. In the present study, a renal

show abstract

“…After myocardial ischemia-reperfusion, EpoR-null mice show an increase in infarct size compared to wild-type mice [7]. EPO pretreatment before ischemia-reperfusion injury conveys significant myocardial protection under moderate hyperglycemic condition through mechanisms involved in the reduction of caspase-3 activity and the upregulation of Bcl-2 in association with enhanced ERK-induced GATA-4 stability [8]. EPO can ameliorate the myocardial inflammatory response in ischemia-reperfusion models, and this beneficial effect is mediated by eNOS-derived NO via PI3-kinase-dependent activation of AP-1 [9].…”

Section: Introductionmentioning

confidence: 99%

Erythropoietin Decreases the Occurrence of Myocardial Fibrosis by Inhibiting the NADPH-ERK-NF-κB Pathway

Wang¹,

Yang²,

Wang³

et al. 2015

Cardiology

View full text Add to dashboard Cite

Objectives: The aim of this study was to investigate the protective role of erythropoietin (EPO) against myocardial fibrosis (MF). Methods: Pressure-overloaded rats were established by abdominal aortic constriction, the rats were randomly divided in a double-blind manner into 3 groups (n = 12 for each group): sham-operated rats (sham), operated rats receiving physiological saline (vehicle) and operated rats receiving 4,000 U/kg rhEPO (EPO group). The vehicle and drugs were administered to rats by intraperitoneal injection. In addition, cultured adult rat cardiac fibroblasts (CFs) were utilized to investigate the role of EPO in CF proliferation and collagen secretion. Results: After 4 weeks, besides an increase in blood pressure, myocardial hypertrophy, collagen deposition in the myocardium and decreased cardiac function were observed in the pressure-overloaded rats. The expression of NADPH oxidase (Nox2 and Nox4) and inflammatory cytokines (CD45, F4/80 and MCP-1) was also significantly increased. All these alterations were prevented by EPO. TGF-ß promoted CF proliferation, collagen secretion, ROS production and Nox2/Nox4 expression, which was inhibited by EPO. In addition, the TGF-ß-induced increase of ERK1/2 phosphorylation and NF-κB expression were attenuated by EPO. Conclusion: EPO inhibited rat MF induced by pressure overload and improved myocardial function by decreasing CF proliferation and differentiation via inhibition of the NADPH-ERK-NF-κB pathway.

show abstract

Erythropoietin protects myocardium against ischemia–reperfusion injury under moderate hyperglycemia

Cited by 22 publications

References 46 publications

Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury

Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling

Erythropoietin Decreases the Occurrence of Myocardial Fibrosis by Inhibiting the NADPH-ERK-NF-κB Pathway

Contact Info

Product

Resources

About