Role of erythropoietin in cortisol-induced hypertension

Kelly, John J.; Martin, Allison; Whitworth, Judith A.

doi:10.1038/sj.jhh.1000959

Cited by 42 publications

(27 citation statements)

References 13 publications

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Section: Discussionmentioning

confidence: 99%

“…Accordingly, treatment of healthy subjects with corticosteroids resulted in a significant increase of serum Epo concentrations. 46 Finally, since an impaired Epo formation in comparison to the degree of ACD was not always observed, especially in children, 43,44 one might suggest that children may harbor a greater capacity than adults to compensate the inhibitory effects of cytokines toward Epo production.Interestingly, we found that in patients with HS, Epo levels were even higher than in IDA subjects although they had comparable hemoglobin levels. In contrast to IDA subjects, HS patients had normal iron levels and no hypoferremia, which indicates that hypoxia as a consequence of anemia rather than iron deficiency is the primary driving force for Epo formation in the kidneys of anemic patients.…”

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confidence: 99%

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Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease

Theurl

Mattle

Seifert

et al. 2006

Blood

165

141

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Anemia of chronic disease (ACD) is frequently found in patients with chronic immune activation. Since most studies on ACD pathophysiology were performed with cell culture or animal models but not in humans, we examined 37 ACD patients suffering from autoimmune diseases or infections, 10 subjects with irondeficiency anemia (IDA), 10 anemic patients with hereditary spherocytosis (HS), and 27 age-matched controls. Although hemoglobin concentrations were comparable between ACD and IDA patients, the latter presented with significantly higher serum erythropoietin concentrations than ACD patients. The significant negative correlation between erythropoietin and hemoglobin levels observed in IDA patients was also found in a group of anemic but not hypoferremic hereditary spherocytosis subjects, but not in ACD patients. Increased serum concentrations of the hepcidin precursor prohepcidin were paralleled by a decreased expression of the iron exporter ferroportin in circulating monocytes of ACD patients. IntroductionAnemia of chronic disease (ACD), also termed as anemia of inflammation, is likewise the most frequent anemia in hospitalized patients. This mild to moderate normocytic to microcytic anemia is found with a frequency between 8% and 95% in patients suffering from diseases that are associated with chronic immune activation, such as autoimmune disorders including rheumatoid arthritis and malignancies and chronic infections including HIV. [1][2][3] At least 3 major immunity-driven mechanisms contribute to the development of ACD. These include the development of hypoferremia with subsequent limitation of iron availability for erythroid progenitor cells, antiproliferative effects of cytokines toward the proliferation and differentiation of erythroid progenitor cells, and, last but not least, an impaired production and reduced biologic activity of erythropoietin (Epo).The development of hypoferremia results from a complex interaction of acute-phase proteins and cytokines together with an anticipated reduction in the lifespan of erythrocytes. Thereby, the absorption of iron from the gut is reduced while iron acquisition and retention by cells of the reticulo-endothelial system (RES) is greatly stimulated, leading to the development of iron-restricted erythropoiesis and anemia. The liver-derived acute-phase protein hepcidin plays a central role in this setting, since it reduces both duodenal iron absorption and iron export from monocytes/ macrophages. [4][5][6] These effects can be referred to as interaction of hepcidin with the transmembrane protein ferroportin, 7 which is responsible for the transfer of iron from enterocytes and monocytes/ macrophages to the circulation. 8,9 The expression of hepcidin by hepatocytes is induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6), resulting in the development of hypoferremia in mice within a few hours after injection. 6,10 Moreover, proinflammatory and anti-inflammatory cytokines play an important role in the pathophysiology of ACD by increasing iron accumulation and sto...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease

Theurl

Mattle

Seifert

et al. 2006

Blood

165

141

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show abstract

“…In fact, extensive in vitro studies have shown that glucocorticoids potentiate erythropoiesis (4,18), enhance proliferation and self-renewal of erythroid progenitors (1), stimulate erythropoietin (19) and cooperate with its effects on progenitor cells (20,21). Further, glucocorticoids are essential to stress erythropoiesis as glucocorticoid receptor-deficient mice are unable to mount an adequate erythroid response to hypoxia or blood loss, both in terms of erythroid-colony Normal ranges are represented by the grey area.…”

Section: Discussionmentioning

confidence: 99%

Gender-dependent changes in haematological parameters in patients with Cushing's disease before and after remission

Ambrogio

Martin

Ascoli

et al. 2014

European Journal of Endocrinology

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Objective: Glucocorticoids stimulate several steps in red blood cell (RBC) development; however, little is known on changes in erythroid parameters in patients with Cushing's disease. The aim of this study was to assess both RBC and white blood cell (WBC) parameters in a large cohort of patients with Cushing's disease and report on alterations in the active phase and after surgical remission. Design and methods: A total of 80 patients with Cushing's disease (63 women and 17 men) were studied before and for up to 254 months' follow-up (mean follow-up 65.8G6.71 months) after pituitary/adrenal surgery. Details of blood counts were reviewed and compared with data obtained from a database of healthy subjects. Results: The RBC counts and haemoglobin levels were low in men with active Cushing's disease (over 80% of values in the lowest quartile) and four patients were overtly anaemic, whereas erythrocyte counts and haemoglobin levels were evenly distributed across the normal range in women with active Cushing's disease. Low erythroid parameters were linked to hypogonadism in men with Cushing's disease. Recovery in erythroid parameters occurred slowly after remission of hypercortisolism in men, in parallel with improvements in testosterone levels. Over 50% of patients with active disease presented increased WBC counts, irrespective of gender, and prompt normalisation within 1 month after surgery. Conclusions: Male patients with Cushing's disease present reduced RBC counts and haemoglobin levels, associated with low testosterone concentrations, which resolve over time after remission of hypercortisolism. Anaemia should therefore be regarded as another unfavourable feature in men with Cushing's disease.

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“…GCs can induce hepatic synthesis of angiotensinogen, increase angiotensin II receptor type 1 concentration in the brain and peripheral tissue and enhance both angiotensin II-stimulated inositol phosphate-3 production in vascular smooth muscle cells and its central actions (159,161). GC-induced increase of erythropoietin contributes to vasoconstriction and therefore hypertension (162). Endothelin has been found to be increased in CS patients (163).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Metabolic comorbidities in Cushing's syndrome

Ferraú

Korbonits

2015

European Journal of Endocrinology

145

132

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Cushing's syndrome (CS) patients have increased mortality primarily due to cardiovascular events induced by glucocorticoid (GC) excess-related severe metabolic changes. Glucose metabolism abnormalities are common in CS due to increased gluconeogenesis, disruption of insulin signalling with reduced glucose uptake and disposal of glucose and altered insulin secretion, consequent to the combination of GCs effects on liver, muscle, adipose tissue and pancreas. Dyslipidaemia is a frequent feature in CS as a result of GC-induced increased lipolysis, lipid mobilisation, liponeogenesis and adipogenesis. Protein metabolism is severely affected by GC excess via complex direct and indirect stimulation of protein breakdown and inhibition of protein synthesis, which can lead to muscle loss. CS patients show changes in body composition, with fat redistribution resulting in accumulation of central adipose tissue. Metabolic changes, altered adipokine release, GC-induced heart and vasculature abnormalities, hypertension and atherosclerosis contribute to the increased cardiovascular morbidity and mortality. In paediatric CS patients, the interplay between GC and the GH/IGF1 axis affects growth and body composition, while in adults it further contributes to the metabolic derangement. GC excess has a myriad of deleterious effects and here we attempt to summarise the metabolic comorbidities related to CS and their management in the perspective of reducing the cardiovascular risk and mortality overall.

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Role of erythropoietin in cortisol-induced hypertension

Cited by 42 publications

References 13 publications

Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease

Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease

Gender-dependent changes in haematological parameters in patients with Cushing's disease before and after remission

Metabolic comorbidities in Cushing's syndrome

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