The effect of erythropoietin on interleukin-1β mediated increase in nitric oxide synthesis in vascular smooth muscle cells

Akimoto, Tetsu; Kusano, Eiji; Muto, Shigeaki; Fujita, Nobuya; Okada, Koji; Saito, Toshikazu; Komatsu, Norio; Ono, Sachiko; Ebata, Satoru; Ando, Yasuhiro; Homma, Sumiko; Asano, Yoshihide

doi:10.1097/00004872-199917090-00003

Cited by 33 publications

(33 citation statements)

References 40 publications

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“…In cultured endothelial cells, recombinant Epo may reduce expression of eNOS, whereas in vascular smooth muscle cells Epo raises the cytosolic calcium content of vascular smooth muscle cells by stimulation of protein kinase C and phospholipase C␥1 (2,43,46). However, in these studies, the concentrations of Epo used (20 -250 U/ml) greatly exceeded concentrations observed in plasma after adenoviral-mediated gene transfer of recombinant Epo in our study (ϳ5 U/ml; Table 1).…”

Section: Discussioncontrasting

confidence: 62%

In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

Santhanam

Smith

Nath

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussioncontrasting

confidence: 62%

In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

Santhanam

Smith

Nath

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Subsequently, a number of published studies have documented biological effects of EPO on vascular smooth muscle and endothelial cells. 8,[34][35][36][37] In all of these in vitro studies the concentrations of EPO used range from 4 to 250 U/ml. 6,8,31,37 While the physiological concentrations of EPO in most healthy animals and humans are in the range of 4-30 mU/ml, up to 100-fold increases can be seen in severe anemias (thus resulting in plasma concentrations as high as 3 U/ml).…”

Section: Discussionmentioning

confidence: 99%

“…8,[34][35][36][37] In all of these in vitro studies the concentrations of EPO used range from 4 to 250 U/ml. 6,8,31,37 While the physiological concentrations of EPO in most healthy animals and humans are in the range of 4-30 mU/ml, up to 100-fold increases can be seen in severe anemias (thus resulting in plasma concentrations as high as 3 U/ml). 36,38 Furthermore, relatively high EPO plasma concentrations in the order of 1-5 U/ml may be obtained intermittently in patients immediately after intravenous injection of the hormone.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide suppresses EPO-induced monocyte chemoattractant protein-1 in endothelial cells: implications for atherogenesis in chronic renal disease

Desai

Zhao

Lankford

et al. 2006

Laboratory Investigation

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Patients with advanced chronic renal disease (CRD) suffer from excessive morbidity and mortality due to complications of accelerated atherosclerosis. Approximately 90% of dialysis-dependent end stage renal disease patients suffer from anemia. Recombinant human erythropoietin (EPO) in combination with iron has become widely used to treat anemic CRD patients. While treatment with EPO results in improved quality of life it may also contribute to the development of atherosclerosis. Recent studies suggest that a reduction in nitric oxide (NO) availability may be linked to EPO-induced vascular dysfunction. Furthermore, CRD per se is thought to result in a state of NO deficiency. The present study suggests that EPO may exert proatherogenic activity by augmenting the cytokine-induced expression of monocyte-chemoattractant protein-1 (MCP-1) in human umbilical vein endothelial cells (HUVECs) and by stimulating the proliferation of HUVECs and human vascular smooth muscle cells (HVSMCs). Augmentation of MCP-1 expression appears to be linked to EPO-induced downregulation of endothelial NO synthase (ecNOS). NO released from a series of synthetic donor compounds suppressed the EPO-mediated augmentation of cytokine-induced MCP-1 expression. In vitro studies revealed that EPO reduces ecNOS expression at both the protein and mRNA levels and that EPO also mediates a reduction in ecNOS enzymatic activity. These observations suggest potential mechanisms through which EPO may contribute to the development of accelerated atherosclerosis, particularly in the setting of CRD where NO availability may already be compromised.

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“…Furthermore, EPO can decrease the plasma iron concentration and increase the ability of plasma to inhibit lipid peroxidation [79,80]. The inhibitory effect of EPO on iNOS has been shown to require the activation of the phospholipase Cγ1 and protein kinase C pathway [81].…”

Section: Antioxidant Properties Of Epo During Ali/ardsmentioning

confidence: 99%

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

Kakavas

Demestiha

Vasileiou

et al. 2010

Eur J Clin Pharmacol

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Current pharmacotherapy for acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) is not optimal, while the biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments or agents with pleiotropic action. In this regard, exogenous erythropoietin (EPO) represents a possible candidate since a number of preclinical studies have revealed beneficial effects of EPO administration in various experimental models of ALI. Taken together, this treatment strategy is not a single mediator approach, but it rather provides protection by modulating multiple levels of early signaling pathways involved in apoptosis, inflammation and peroxidation, potentially restoring overall homeostasis. Furthermore, EPO appears to confer vascular protection by promoting angiogenesis. However, only preliminary studies exist and more experimental and clinical studies are necessary for the clarification of the efficacy and potentially cytoprotective mechanisms of EPO action. In addition to the attempts to optimize the dose and timing of EPO administration, it would be of great value to minimize any potential toxicity, which is essential for EPO to fulfil its role as a potential candidate for the treatment of ALI in routine clinical practice. The present article reviews recent advances that have elucidated biological and biochemical activities of EPO which may be potentially applicable for ALI/ARDS management.

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The effect of erythropoietin on interleukin-1β mediated increase in nitric oxide synthesis in vascular smooth muscle cells

Abstract: rHuEPO inhibits IL-1beta induced NO production by suppressing iNOS mRNA and protein expressions through EpoR, and the PLC-gamma1 and PKC pathway may be involved.

Cited by 33 publications

References 40 publications

In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

In vivo stimulatory effect of erythropoietin on endothelial nitric oxide synthase in cerebral arteries

Nitric oxide suppresses EPO-induced monocyte chemoattractant protein-1 in endothelial cells: implications for atherogenesis in chronic renal disease

Erythropoetin as a novel agent with pleiotropic effects against acute lung injury

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