Erythropoietin protects the systolic function of neonatal hearts against ischaemia/reperfusion injury

Vilarinho, Karlos Alexandre Souza; Oliveira, Pedro Paulo Martins de; Saad, Mário José Abdalla; Eghtesady, Pirooz; Filho, Lindemberg Mota Silveira; Vieira, Reinaldo Wilson; Petrucci, Orlando

doi:10.1093/ejcts/ezs254

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…Experimental data indicate that EPO maintains the integrity of endothelial cells through an eNOS-dependent mechanism, and deletion of EPO or EPOR leads to angiogenic defects in the vascular system during embryogenesis [ 7 , 8 , 17 , 40 , 41 ]. Moreover, EPO improves cardiac function by increasing blood flow and inhibiting myocyte apoptosis in ischemia rodent models [ 42 , 43 ]. On the contrary, clinical observations demonstrate that the mortality and morbidity rate are elevated in patients with acute ischemia stroke or chronic kidney diseases when administrated with EPO [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

β Common Receptor Mediates Erythropoietin‐Conferred Protection on OxLDL‐Induced Lipid Accumulation and Inflammation in Macrophages

Lee¹,

Lu²,

et al. 2015

Mediators of Inflammation

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Erythropoietin (EPO), the key factor for erythropoiesis, also protects macrophage foam cells from lipid accumulation, yet the definitive mechanisms are not fully understood. β common receptor (βCR) plays a crucial role in the nonhematopoietic effects of EPO. In the current study, we investigated the role of βCR in EPO-mediated protection in macrophages against oxidized low-density lipoprotein- (oxLDL-) induced deregulation of lipid metabolism and inflammation. Here, we show that βCR expression was mainly in foamy macrophages of atherosclerotic aortas from apolipoprotein E-deficient mice. Results of confocal microscopy and immunoprecipitation analyses revealed that βCR was colocalized and interacted with EPO receptor (EPOR) in macrophages. Inhibition of βCR activation by neutralizing antibody or small interfering RNA (siRNA) abolished the EPO-conferred protection in oxLDL-induced lipid accumulation. Furthermore, EPO-promoted cholesterol efflux and upregulation of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 were prevented by pretreatment with βCR neutralizing antibody or βCR siRNA. Additionally, blockage of βCR abrogated the EPO-conferred anti-inflammatory action on oxLDL-induced production of macrophage inflammatory protein-2. Collectively, our findings suggest that βCR may play an important role in the beneficial effects of EPO against oxLDL-elicited dysfunction of macrophage foam cells.

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Section: Discussionmentioning

confidence: 99%

β Common Receptor Mediates Erythropoietin‐Conferred Protection on OxLDL‐Induced Lipid Accumulation and Inflammation in Macrophages

Lee¹,

Lu²,

et al. 2015

Mediators of Inflammation

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“…Samples of the LV tissue were snap-frozen in liquid nitrogen and stored at -80°C. Total protein extraction was performed using RIPA buffer (1% (w/w) Nonidet P40, 1% (w/w) sodiumdeoxycate, 0.1% (w/v) SDS, 150mmol/L NaCl, 50mmol/L HEPES pH 7.0, 2mmol/L EDTA pH 8.0, 100mmol/L NaF, 10% glycerol, 1.5mmol/L MgCl 2 , 100mmol/L PMSF in ETOH, 200mmol/L sodium orthovanadate, 1 μg/ml aprotin), and samples were homogenized and centrifuged prior to the determination of protein concentration in supernatants as previously described [ 20 ]. Protein extracts (125 μg) were separated using 8% or 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to nitrocellulose membranes.…”

Section: Methodsmentioning

confidence: 99%

Diacerein Improves Left Ventricular Remodeling and Cardiac Function by Reducing the Inflammatory Response after Myocardial Infarction

et al. 2015

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BackgroundThe inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo.Methods and ResultsLigation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription.ConclusionsTreatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway.

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“…Erythropoietin (EPO) − a hormone best known for its effect on red blood cell production − has been shown to protect organs and tissues from ischemia and reperfusion injury including the heart [3]–[7], brain [8], [9], spinal cord [10], [11], kidney [12]–[14], liver [13]–[15], and skin [16], [17]. We have reported beneficial effects of EPO for resuscitation from cardiac arrest in animal models [18]–[20] and in human victims of sudden cardiac arrest [21].…”

Section: Introductionmentioning

confidence: 99%

Effects of Intraosseous Erythropoietin during Hemorrhagic Shock in Swine

et al. 2014

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ObjectiveTo determine whether erythropoietin given during hemorrhagic shock (HS) ameliorates organ injury while improving resuscitation and survival.MethodsThree series of 24 pigs each were studied. In an initial series, 50% of the blood volume (BV) was removed in 30 minutes and normal saline (threefold the blood removed) started at minute 90 infusing each third in 30, 60, and 150 minutes with shed blood reinfused at minute 330 (HS-50BV). In a second series, the same HS-50BV protocol was used but removing an additional 15% of BV from minute 30 to 60 (HS-65BV). In a final series, blood was removed as in HS-65BV and intraosseous vasopressin given from minute 30 (0.04 U/kg min−1) until start of shed blood reinfusion at minute 150 (HS-65BV+VP). Normal saline was reduced to half the blood removed and given from minute 90 to 120 in half of the animals. In each series, animals were randomized 1∶1 to receive erythropoietin (1,200 U/kg) or control solution intraosseously after removing 10% of the BV.ResultsIn HS-50BV, O2 consumption remained near baseline yielding minimal lactate increases, 88% resuscitability, and 60% survival at 72 hours. In HS-65BV, O2 consumption was reduced and lactate increased yielding 25% resuscitability. In HS-65BV+VP, vasopressin promoted hemodynamic stability yielding 92% resuscitability and 83% survival at 72 hours. Erythropoietin did not affect resuscitability or subsequent survival in any of the series but increased interleukin-10, attenuated lactate increases, and ameliorated organ injury based on lesser troponin I, AST, and ALT increases and lesser neurological deficits in the HS-65BV+VP series.ConclusionsErythropoietin given during HS in swine failed to alter resuscitability and 72 hour survival regardless of HS severity and concomitant treatment with fluids and vasopressin but attenuated acute organ injury. The studies also showed the efficacy of vasopressin and restrictive fluid resuscitation for hemodynamic stabilization and survival.

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Erythropoietin protects the systolic function of neonatal hearts against ischaemia/reperfusion injury

Abstract: EPO had a protective effect on neonatal systolic function after ischaemia/reperfusion injury, but no effect on diastolic function. This cardioprotective effect might be mediated by the activation of the Akt pathway.

Cited by 7 publications

References 22 publications

β Common Receptor Mediates Erythropoietin‐Conferred Protection on OxLDL‐Induced Lipid Accumulation and Inflammation in Macrophages

β Common Receptor Mediates Erythropoietin‐Conferred Protection on OxLDL‐Induced Lipid Accumulation and Inflammation in Macrophages

Diacerein Improves Left Ventricular Remodeling and Cardiac Function by Reducing the Inflammatory Response after Myocardial Infarction

Effects of Intraosseous Erythropoietin during Hemorrhagic Shock in Swine

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