ArticleBritish journal of pharmacology2010
Darbepoetin-mediated cardioprotection after myocardial infarction involves multiple mechanisms independent of erythropoietin receptor-common beta-chain heteroreceptor.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the β-common receptor in mice with cerebral ischemic stroke.CNS neuroscience & therapeutics · 2024Article
- Is the β Common Receptor the Key Molecule for the Protective Effect of Erythropoietin?Aging and disease · 2023Article
- Low-Dose Erythropoietin Amplifies Beneficial Effects of Angiotensin II Blockade on Glomerulosclerosis.Laboratory investigation; a journal of technical methods and pathology · 2023Article
- Second-generation non-hematopoietic erythropoietin-derived peptide for neuroprotection.Redox biology · 2022Article
- Crosstalk between cytotoxic CD8+ T cells and stressed cardiomyocytes triggers development of interstitial cardiac fibrosis in hypertensive mouse hearts.Frontiers in immunology · 2022Article
- The Many Facets of Erythropoietin Physiologic and Metabolic Response.Frontiers in physiology · 2019Review
- EPO does not promote interaction between the erythropoietin and beta-common receptors.Scientific reports · 2018Article
- EPORBioscience reports · 2017Article
- p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation.Cellular signalling · 2013Article
- Erythropoietin neuroprotection with traumatic brain injury.Pathophysiology : the official journal of the International Society for Pathophysiology · 2013Article
- Effects of heme oxygenase-1 upregulation on blood pressure and cardiac function in an animal model of hypertensive myocardial infarction.International journal of molecular sciences · 2013Article
- Regulation of Erythropoietin Receptor Activity in Endothelial Cells by Different Erythropoietin (EPO) Derivatives: An in Vitro Study.International journal of molecular sciences · 2013Article
- The receptor that tames the innate immune response.Molecular medicine (Cambridge, Mass.) · 2012Review
- Improved cerebrovascular function and reduced histological damage with darbepoietin alfa administration after cortical impact injury in rats.The Journal of pharmacology and experimental therapeutics · 2011Article
- Non-erythroid effects of erythropoietin.Haematologica · 2010Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeDarbepoetin, a long-acting erythropoietin derivative, attenuates cardiomyocyte apoptosis and improves short-term (3 days) cardiac function, but the mechanisms responsible are unknown. We investigated potential mechanisms by which darbepoetin exerts cardioprotection following myocardial infarction in mice and the significance of the erythropoietin receptor (EPOR)-common beta-chain (c-beta-chain) heteroreceptor. EXPERIMENTAL APPROACH: Mice underwent 60 min coronary occlusion followed by treatment with vehicle or a single dose of darbepoetin. Effects on gene expression, apoptosis and neutrophil accumulation in infarcted left ventricle were assessed 24 h later. Cardiac function, effects on vascularization and fibrosis were assessed 28 days later. The significance of EPOR-c-beta-chain heteroreceptor was examined 28 days after infarction using mice deficient in c-beta-chain. KEY
resultsTwenty-four hours after darbepoetin, mRNAs encoding haeme oxygenase-1 (HO-1), iNOS and brain natriuretic peptide (BNP) were markedly elevated only in infarcted regions, and the frequency of apoptotic cells attenuated. Inflammation was also attenuated with reductions in neutrophil numbers. Darbepoetin also elevated mRNAs encoding angiogenic factors: placental growth factor, monocyte chemoattractant protein-1 and interleukin-1beta. Twenty-eight days after treatment, CD31+ vessels in the infarct zone doubled and fibrosis reduced. Cardiac haemodynamics were improved. Darbepoetin also improved cardiac haemodynamics in c-beta-chain-deficient mice, increased HO-1 and iNOS expression and vessel numbers and attenuated fibrosis. CONCLUSIONS AND IMPLICATIONS: Darbepoetin stimulates expression of haeme oxygenase, iNOS, BNP and angiogenic factors specifically in infarcted left ventricle that attenuates inflammation, apoptosis and fibrosis; elevate vessel numbers; and improve cardiac function. The EPOR-c-beta-chain heteroreceptor is not essential for these effects.
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