Potential anti-inflammatory effect of erythropoietin in non-clinical studies in vivo: A systematic review

Silva, Inês; Alípio, Carolina; Pinto, Rui; Mateus, Vanessa

doi:10.1016/j.biopha.2021.111558

Cited by 17 publications

(19 citation statements)

References 89 publications

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“…4 Several studies proved that the expression of FTO was up-regulated and correlated with the m6A level of mRNA in GC by the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database analysis. 34,35 In addition, FTO was also over-expressed in GC samples from Chinese cohort by performing RT-qPCR, Western blot and immunohistochemistry (IHC), showing good agreement with the results of databases. 36,37 And the epidemiological and clinical characteristics investigations revealed that the FTO expression was associated with age, differentiation, lymph node metastasis, TNM stage, and prognosis in GC patients.…”

Section: Fto Dysregulation In Digestive System Cancers Gastric Cancer (Gc)supporting

confidence: 62%

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers

Liu

Yang

Zhang

et al. 2021

CMAR

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Digestive system cancers are common cancers with high cancer deaths worldwide. They have become a major threat to public health and economic burden. As one of the most universal RNA modifications in eukaryotes, the N6-methyladenosine (m6A) modification is involved in the occurrence, development, prognosis, and treatment response of various cancers, including digestive system cancers. M6A demethylases shape the m6A landscape dynamically, playing important roles in cancers. In addition, accumulating evidence reveal that many environmental toxicants are the established risk factors for digestive system cancers and associated with m6A modification. In this review, we summarize the multiple functions of M6A demethylases (fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and AlkB homolog 3 (ALKBH3)) in digestive system cancers, which are aberrantly expressed and affect cancer progression. We also discuss the potential roles of m6A demethylases in the assessment of environmental exposure, the signature for prevention and diagnosis of digestive system cancers.

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Section: Fto Dysregulation In Digestive System Cancers Gastric Cancer (Gc)supporting

confidence: 62%

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers

Liu

Yang

Zhang

et al. 2021

CMAR

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“…ACE I/D polymorphism genetic testing could be predictive and guide patient triage and treatment decision making as individuals with the DD genotype are predisposed to a more severe COVID-19 disease course[ 59 ]. Research evidence supports the notion that endogenously[ 109 , 112 ] and exogenously increased EPO levels[ 123 ] could break the vicious circle of persistent ACE D allele augmented Ang II stimulation on PAI-1, IL-6 and FGF23 by both synergistic and individual inhibition[ 21 , 122 , 123 , 127 , 134 ]. Whenever the administration of rhEPO is not possible due to contraindications or heightened prothrombotic risk, EPO derivatives can coax EPO’s tissue-protective activity via its TPR for therapeutic use without the risks attributed to EPO’s hematological actions[ 10 , 14 , 134 ].…”

Section: Therapeutic Considerationsmentioning

confidence: 84%

“…Research evidence supports the notion that endogenously[ 109 , 112 ] and exogenously increased EPO levels[ 123 ] could break the vicious circle of persistent ACE D allele augmented Ang II stimulation on PAI-1, IL-6 and FGF23 by both synergistic and individual inhibition[ 21 , 122 , 123 , 127 , 134 ]. Whenever the administration of rhEPO is not possible due to contraindications or heightened prothrombotic risk, EPO derivatives can coax EPO’s tissue-protective activity via its TPR for therapeutic use without the risks attributed to EPO’s hematological actions[ 10 , 14 , 134 ]. Furthermore, EPO mediates reduction of auto-and alloantibody formation and used together with LXA4 inducing BALs and/or ASA could prevent recently reported AT1-AA induced collateral damage and autoimmune pathology[ 94 , 101 , 102 , 135 , 136 ].…”

Section: Therapeutic Considerationsmentioning

confidence: 84%

Age and genotype dependent erythropoietin protection in COVID-19

Papadopoulos

Sutheesophon

Manipalviratn³

et al. 2021

WJSC

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Erythropoietin (EPO) is the main mediator of erythropoiesis and an important tissue protective hormone that appears to mediate an ancestral neuroprotective innate immune response mechanism at an early age. When the young brain is threatened-prematurity, neonatal hyperbilirubinemia, malaria- EPO is hyper-secreted disproportionately to any concurrent anemic stimuli. Under eons of severe malarial selection pressure, neuroprotective EPO augmenting genetic determinants such as the various hemoglobinopathies, and the angiotensin converting enzyme (ACE) I/D polymorphism, have been positively selected. When malarial and other cerebral threats abate and the young child survives to adulthood, EPO subsides. Sustained high ACE and angiotensin II (Ang II) levels through the ACE D allele in adulthood may then become detrimental as witnessed by epidemiological studies. The ubiquitous renin angiotensin system (RAS) influences the α-klotho/fibroblast growth factor 23 (FGF23) circuitry, and both are interconnected with EPO. Here we propose that at a young age, EPO augmenting genetic determinants through ACE D allele elevated Ang II levels in some or HbE/beta thalassemia in others would increase EPO levels and shield against coronavirus disease 2019, akin to protection from malaria and dengue fever. Human evolution may use ACE2 as a “bait” for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to gain cellular entry in order to trigger an ACE/ACE2 imbalance and stimulate EPO hypersecretion using tissue RAS, uncoupled from hemoglobin levels. In subjects without EPO augmenting genetic determinants at any age, ACE2 binding and internalization upon SARS-CoV-2 entry would trigger an ACE/ACE2 imbalance, and Ang II oversecretion leading to protective EPO stimulation. In children, low nasal ACE2 Levels would beneficially augment this imbalance, especially for those without protective genetic determinants. On the other hand, in predisposed adults with the ACE D allele, ACE/ACE2 imbalance, may lead to uncontrolled RAS overactivity and an Ang II induced proinflammatory state and immune dysregulation, with interleukin 6 (IL-6), plasminogen activator inhibitor, and FGF23 elevations. IL-6 induced EPO suppression, aggravated through co-morbidities such as hypertension, diabetes, obesity, and RAS pharmacological interventions may potentially lead to acute respiratory distress syndrome, cytokine storm and/or autoimmunity. HbE/beta thalassemia carriers would enjoy protection at any age as their EPO stimulation is uncoupled from the RAS system. The timely use of rhEPO, EPO analogs, acetylsalicylic acid, bioactive lipids, or FGF23 antagonists in genetically predisposed individuals may counteract those detrimental effects.

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“…In experimental mouse models in which EPOR is lacking in non-hematopoietic cells, left ventricular myocardial stress was found to lead to significantly greater left ventricular mass and less cardiac contractility than those in control mice, concomitant with decreased signal transducer and activator of transcription 3 (STAT3) signaling required for cardioprotection [ 15 ]. Second, the effect of the anti-inflammatory action of erythropoietin [ 34 , 35 ] might be blocked by anti-EPOR antibodies. The inflammatory milieu has been reported to cause the downregulation of EPOR [ 36 ], hyporesponsiveness of ESA [ 37 ], and increase in fibroblast growth factor 23 [ 36 ], which induced myocardial hypertrophy [ 38 , 39 ] and diastolic dysfunction [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Anti-Erythropoietin Receptor Antibodies and Cardiac Function in Patients on Hemodialysis: A Multicenter Cross-Sectional Study

et al. 2022

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Cardiac dysfunction is an important prognostic predictor of cardiovascular mortality in patients on hemodialysis (HD). Erythropoietin (EPO) has been reported to improve cardiac function by binding to the EPO receptor (EPOR) on cardiomyocytes. This study investigated whether anti-EPOR antibodies were associated with left ventricular cardiac function in patients undergoing HD. This multicenter, cross-sectional observational study included 377 patients (median age, 70 years; 267 (70%) males) with chronic kidney disease (CKD) undergoing stable maintenance HD. Serum levels of anti-EPOR antibodies were measured, and echocardiography was used to assess the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Anti-EPOR antibodies were found in 17 patients (4.5%). LVMI was greater (median of 135 g/m2 vs. 115 g/m2, p = 0.042), and the prevalence of LVEF < 50% was higher (35.3% vs. 15.6%, p = 0.032) in patients with anti-EPOR antibodies than in those without. Multivariable linear regression and logistic regression analysis (after adjusting for known risk factors of heart failure) revealed that anti-EPOR antibodies were independently associated with LVMI (coefficient 16.2%; 95% confidence interval (CI) 1.0–35.0%, p = 0.043) and LVEF <50% (odds ratio 3.20; 95% CI 1.05–9.73, p = 0.041). Thus, anti-EPOR antibody positivity was associated with left ventricular dysfunction in patients undergoing HD.

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Potential anti-inflammatory effect of erythropoietin in non-clinical studies in vivo: A systematic review

Cited by 17 publications

References 89 publications

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers

Emerging Roles of N6-Methyladenosine Demethylases and Its Interaction with Environmental Toxicants in Digestive System Cancers

Age and genotype dependent erythropoietin protection in COVID-19

Association between Anti-Erythropoietin Receptor Antibodies and Cardiac Function in Patients on Hemodialysis: A Multicenter Cross-Sectional Study

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