Erythropoietin Requires Endothelial Nitric Oxide Synthase to Counteract TNF-α-Induced Microcirculatory Dysfunction in Murine Striated Muscle

Contaldo, Claudio; Lindenblatt, Nicole; Elsherbiny, Ahmed; Högger, D.; Borozadi, Meisam Khorrami; Vetter, Stefan; Lang, Karl S.; Handschin, Alexander E.; Giovanoli, Pietro

doi:10.1097/shk.0b013e3181fd0700

Cited by 12 publications

(8 citation statements)

References 33 publications

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“…In addition, the NO leads to up-regulation of EpoR in these cells suggesting a coordinated response of these signaling molecules ( 53 ). In studies of sepsis in which tumor necrosis factor induces microvascular inflammation in striated muscle, Epo ameliorates the microvascular damage by an eNOS dependent mechanism but the protective effect is independent of iNOS ( 54 ). Similarly, Epo prevents sepsis-related acute kidney in rats by up-regulating eNOS ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

et al. 2014

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Background: Erythropoietin (Epo) improves post-traumatic cerebral blood flow (CBF), pressure autoregulation, and vascular reactivity to l-arginine. This study examines the dependence of these cerebral hemodynamic effects of Epo on nitric oxide generated by endothelial nitric oxide synthase (eNOS).Methods: Using laser Doppler flow imaging, CBF was monitored in wild-type (WT) and eNOS-deficient mice undergoing controlled cortical impact followed by administration of Epo (5000 U/kg) or normal saline.Results: Cerebral blood flow decreased in all groups post-injury with the greatest reductions occurring at the impact site. Epo administration resulted in significantly higher CBF in the peri-contusional sites in the WT mice [70.2 ± 3.35% in Epo-treated compared to 53 ± 3.3% of baseline in saline-treated mice (p < 0.0001)], but no effect was seen in the eNOS-deficient mice. No CBF differences were found at the core impact site where CBF dropped to 20–25% of baseline in all groups.Conclusion: These differences between eNOS-deficient and WT mice indicate that the Epo mediated improvement in CBF in traumatic brain injury is eNOS dependent.

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Section: Discussionmentioning

confidence: 99%

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

et al. 2014

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“…The authors conclude that the tissue‐protective effect is mediated by NO originating from the endothelium. This effect has been demonstrated both in wild‐type as well as in iNOS knockout mice (iNOS −/− mice) but not in endothelial (e)NOS knockout mice (eNOS −/− mice) . The authors have also demonstrated in an immunohistochemical assay that activated macrophages were almost not present in the perivenular tissue of EPO‐pretreated wild‐type and iNOS −/− mice when compared to eNOS −/− mice .…”

Section: Epo‐induced Effects In Physiological Wound Healing Of the Skinmentioning

confidence: 79%

“…This effect has been demonstrated both in wild‐type as well as in iNOS knockout mice (iNOS −/− mice) but not in endothelial (e)NOS knockout mice (eNOS −/− mice) . The authors have also demonstrated in an immunohistochemical assay that activated macrophages were almost not present in the perivenular tissue of EPO‐pretreated wild‐type and iNOS −/− mice when compared to eNOS −/− mice . The current data obtained from in vivo experiments imply the following: The pleiotropic functions of EPO are most probably triggered by a variety of mechanisms that are either dependent or independent of NO.…”

Section: Epo‐induced Effects In Physiological Wound Healing Of the Skinmentioning

confidence: 98%

“…The current data obtained from in vivo experiments imply the following: The pleiotropic functions of EPO are most probably triggered by a variety of mechanisms that are either dependent or independent of NO. As the rolling and sticking of leukocytes remained almost unaffected in EPO‐pretreated eNOS −/− animals, one could conclude that eNOS, but not iNOS, may play a pivotal role in EPO‐mediated anti‐inflammatory effects …”

Section: Epo‐induced Effects In Physiological Wound Healing Of the Skinmentioning

confidence: 99%

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The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

Sorg

Harder

Krueger

et al. 2012

Medicinal Research Reviews

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Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound‐healing phases in a dose‐dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound‐healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.

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“…One of the mechanism of EPO protection against TNF-α depends on NO derived from endothelial cells [53]. …”

Section: The Influence Of Epo On Inflammation and Fibrosismentioning

confidence: 99%

The influence of the pleiotropic action of erythropoietin and its derivatives on nephroprotection

Rysz

2013

Med Sci Monit

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Erythropoietin (EPO) is traditionally described as a hematopoietic cytokine or growth hormone regulating proliferation, differentiation, and survival of erythroid progenitors. The use of EPO in patients with chronic kidney disease (CKD) was a milestone achievement in the treatment of anemia. However, EPO involves some degree of risk, which increases with increasing hemoglobin levels. A growing number of studies have assessed the renoprotective effects of EPO in acute kidney injury (AKI) or CKD. Analysis of the biological effects of erythropoietin and pathophysiology of CKD in these studies suggests that treatment with erythropoiesis-stimulating agents (ESAs) may exert renoprotection by pleiotropic actions on several targets and directly or indirectly slow the progression of CKD. By reducing ischemia and oxidative stress or strengthening anti-apoptotic processes, EPO may prevent the development of interstitial fibrosis and the destruction of tubular cells. Furthermore, it could have a direct protective impact on the integrity of the interstitial capillary network through its effects on endothelial cells and promotion of vascular repair, or modulate inflammation response. Thus, it is biologically plausible to suggest that correcting anemia with ESAs could slow the progression of CKD.The aim of this article is to discuss these possible renoprotection mechanisms and provide a comprehensive overview of erythropoietin and its derivatives.

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Erythropoietin Requires Endothelial Nitric Oxide Synthase to Counteract TNF-α-Induced Microcirculatory Dysfunction in Murine Striated Muscle

Cited by 12 publications

References 33 publications

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

Endothelial Nitric Oxide Synthase Mediates the Cerebrovascular Effects of Erythropoietin in Traumatic Brain Injury

The Nonhematopoietic Effects of Erythropoietin in Skin Regeneration and Repair: From Basic Research to Clinical Use

The influence of the pleiotropic action of erythropoietin and its derivatives on nephroprotection

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