Effects of erythropoietin on angiogenesis after myocardial infarction in porcine

Kawachi, K; Iso, Yoshitaka; Sato, Takatoshi; Wakabayashi, Kohei; Kobayashi, Youichi; Takeyama, Youichi; Suzuki, Hiroshi

doi:10.1007/s00380-011-0197-2

Cited by 27 publications

(13 citation statements)

References 36 publications

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“…[6] In addition, the PI3K/Akt signaling also mediates angiogenesis and VEGF expression in the ECs. [789] Wang et al . [10] found that the rh-EPO increased the mobilization of endothelial progenitor cells (EPCs) and subsequent promotion of angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

Zhu

Jiang

2017

Chinese Medical Journal

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Background:Recombinant human-erythropoietin (rh-EPO) has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation. In the present study, we found that the rh-EPO was related to the promotion of neovascularization. Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway.Methods:Postnatal day 5 (PD5), rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h. All the rat pups were randomized into five groups as follows: (1) control group; (2) hypoxia-ischemic (HI) group; (3) HI + LY294002 group; (4) HI + rh-EPO group; and (5) HI + rh-EPO + LY294002 group. The phospho-Akt protein was tested 90 min after the whole operation, and CD34, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor (VEGF) were also tested 2 days after the whole operation.Results:In the hypoxic and ischemic zone of the premature rat brain, the rh-EPO induced CD34+ cells to immigrate to the HI brain zone (P < 0.05) and also upregulated the VEGFR2 protein expression (P < 0.05) and VEGF mRNA level (P < 0.05) through the PI3K/Akt (P < 0.05) signaling pathway when compared with other groups.Conclusions:The rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway. Besides, the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

Zhu

Jiang

2017

Chinese Medical Journal

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“…Erythropoietin has recently been shown to confer cardioprotective effects via angiogenesis and antiapoptosis in porcine myocardial injury [11]. Sulfur dioxide can decrease the activated ERS in rats with myocardial injury [12].…”

Section: Introductionmentioning

confidence: 99%

LipoxinA4 attenuates myocardial ischemia reperfusion injury via a mechanism related to downregulation of GRP-78 and caspase-12 in rats

Zhao

Shao

et al. 2013

Heart Vessels

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This study aims to determine the effect of Lipoxin (LX)A4 on myocardial ischemia reperfusion injury (MIRI) in rats and the related molecular mechanisms. Male SD rats were divided into six groups. The sham operation groups (groups C1, C2) were injected with 2 ml/kg normal saline before and after coronary artery threading, respectively. The MIRI group (groups I/R1, I/R2) were injected with normal saline before and after MIRI, respectively. The LXA4 groups (groups LX1, LX2) were injected with LXA4 before and after MIRI treatment, respectively. The hematoxylin–eosin staining and ultrastructural changes of cardiac muscle were observed. The serum levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF) α and cardiac troponin I (cTnI) were measured before open-chest operation and at the end of the experiment. The mRNA and protein levels of GRP-78 and caspase-12 were determined in each group. The myocardial cell apoptosis, myeloperoxidase (MPO), superoxide dismutase (SOD), and malondialdehyde (MDA) contents were detected. The mRNA and protein levels of GRP-78 and caspase-12, the apoptosis, the serum IL-1β, IL-6, IL-10, TNF-α, and cTnI concentrations, MPO, SOD, MDA contents were significantly increased in groups I/R1, I/R2, LX1, and LX2 compared with those in groups C1 and C2 (P < 0.05). The mRNA and protein expression levels of GRP-78 and caspase-12 in groups LX1 and LX2 were lower than those in groups I/R1 and I/R2. Compared with group I/R1 and I/R2, the myocardial neutrophil infiltration and ultrastructure damage were significantly less in groups LX1 and LX2. GRP-78 and IL-10 are expressed both extracellularly and intracellularly, but are mainly expressed in the cytoplasms. In the absence of MIRI, LXA4 has no detectable effect on GRP-78 and caspase-12 expression. Before and after MIRI, application of LXA4 significantly inhibits neutrophil activation, and attenuates myocardial inflammatory injury and oxidative stress. LXA4 downregulates the mRNA and protein expression of GRP-78 and caspase-12. LXA4 could play a role in myocardial protection via a mechanism related to downregulation of GRP-78 and caspase-12, and inhibition of apoptosis.

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“…In the present study systemic absorption was limited, as EPO was contained at the defect site—because of the almost avascular nature of the calvaria, and because of the fact that bone defects were sealed with bone wax (Wiltfang et al 2002). These measures were taken because porcine EPO has 80% DNA sequence homology with human EPO, and several groups have reported hematopoietic and pleiotropic effects of human recombinant EPO in swine (Wen et al 1993, Kawachi et al 2012). We studied the effect of EPO compared to within-subject saline controls by performing pairwise comparisons within the collagen carrier group, the autograft group, and the PCL scaffold group, and no comparisons between the 3 different treatment modalities were performed.…”

Section: Discussionmentioning

confidence: 99%

A single topical dose of erythropoietin applied on a collagen carrier enhances calvarial bone healing in pigs

Rölfing

Jensen

et al. 2014

Acta Orthopaedica

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Background and purposeThe osteogenic potency of erythropoietin (EPO) has been documented. However, its efficacy in a large-animal model has not yet been investigated; nor has a clinically safe dosage. The purpose of this study was to overcome such limitations of previous studies and thereby pave the way for possible clinical application. Our hypothesis was that EPO increases calvarial bone healing compared to a saline control in the same subject.MethodsWe used a porcine calvarial defect model. In each of 18 pigs, 6 cylindrical defects (diameter: 1 cm; height: 1 cm) were drilled, allowing 3 pairwise comparisons. Treatment consisted of either 900 IU/mL EPO or an equal volume of saline in combination with either autograft, a collagen carrier, or a polycaprolactone (PCL) scaffold. After an observation time of 5 weeks, the primary outcome (bone volume fraction (BV/TV)) was assessed with high-resolution quantitative computed tomography. Secondary outcome measures were histomorphometry and blood samples.ResultsThe median BV/TV ratio of the EPO-treated collagen group was 1.06 (CI: 1.02–1.11) relative to the saline-treated collagen group. Histomorphometry showed a similar median effect size, but it did not reach statistical significance. Autograft treatment had excellent healing potential and was able to completely regenerate the bone defect independently of EPO treatment. Bony ingrowth into the PCL scaffold was sparse, both with and without EPO. Neither a substantial systemic effect nor adverse events were observed. The number of blood vessels was similar in EPO-treated defects and saline-treated defects.InterpretationTopical administration of EPO on a collagen carrier moderately increased bone healing. The dosing regime was safe, and could have possible application in the clinical setting. However, in order to increase the clinical relevance, a more potent but still clinically safe dose should be investigated.

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Effects of erythropoietin on angiogenesis after myocardial infarction in porcine

Cited by 27 publications

References 36 publications

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

LipoxinA4 attenuates myocardial ischemia reperfusion injury via a mechanism related to downregulation of GRP-78 and caspase-12 in rats

A single topical dose of erythropoietin applied on a collagen carrier enhances calvarial bone healing in pigs

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