Abstract
Early growth response- (Egr-) 1 is an upstream master switch in controlling inflammatory responses following myocardial ischemia-reperfusion (I/R). Activation of extracellular signal-regulated protein kinase-1 and kinase-2 (ERK1/2) signaling is known to upregulate Egr-1. ERK1/2 pathway has been previously shown to mediate the therapeutic action of electroacupucture (EA). Thus, we hypothesized that EA would reduce myocardial I/R injury and inflammatory responses through inhibiting Egr-1 expression via the ERK1/2 pathway. Mice were pretreated with EA, U0126, or combination of EA and U0126 and then underwent 1 h myocardial ischemia and 3 h reperfusion. We investigated that EA significantly attenuated the I/R-induced upregulation of both Egr-1 and phosporylated-ERK1/2 (p-ERK1/2), decreased myocardial inflammatory cytokines including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and reduced the infarct size and the release of cardiac troponin I (cTnI). U0126 treatment also exhibited the same effect as EA on Egr-1 level and subsequent cardioprotective effects. There was no additive effect of cotreatment with EA and U0126 on the expression of Egr-1 and its downstream target genes (TNF-α, IL-1β) or serum cTnI level. Collectively, these observations suggested that EA attenuates myocardial I/R injury, possibly through inhibiting the ERK1/2-Egr-1 signaling pathway and reducing the release of proinflammatory cytokines.
Highlights
Acupuncture is a therapeutic technique that originated in China more than five thousand years ago [1]
Accumulating evidences from experimental studies indicated that EA at selected acupoints [e.g., Neiguan (PC6)] can reduce myocardial ischemia-reperfusion (I/R) injury, as reflected by reducing release of myocardial enzyme such as cardiac troponin I (cTnI) and creatine phosphokinase (CPK) [2, 3], attenuating the frequency and severity of arrhythmias [4, 5] and decreasing infarct size [6,7,8]
Using 3 h of reperfusion, we tested the effects of EA on myocardial Early growth response- (Egr-)1 and p-extracellular signal-regulated protein kinase-1 and kinase-2 (ERK1/2) levels
Summary
Acupuncture is a therapeutic technique that originated in China more than five thousand years ago [1]. The beneficial effects of EA have been observed in clinical settings, where it has resulted in reduced cTnI release, decreased C-reactive protein level, and shorter intensive care unit stay in both adult and pediatric patients receiving heart surgeries [2, 9]. Despite these visible benefits of EA, the underlying molecular mechanisms of EAmediated cardiac protection remain unclear. It is reported that EA at PC6 acupoints alleviates cardiac hypertrophy after myocardial infarction by inhibiting the activation of ERK1/2 pathway [16]. We tested the hypothesis that EA attenuates myocardial I/R injury by inhibiting the ERK1/2-Egr-1 pathway
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