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Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin
Heart failure (HF)-associated anemia is common and has a poor outcome. Because bone marrow (BM) dysfunction may contribute to HF-associated anemia, we first investigated mechanisms of BM dysfunction in an established model of HF, the transgenic REN2 rat, which is characterized by severe hypertrophy...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Springer-Verlag
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056002/ https://www.ncbi.nlm.nih.gov/pubmed/21191566 http://dx.doi.org/10.1007/s00109-010-0710-6 |
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author | Ruifrok, Willem-Peter T. Qian, Cheng Silljé, Herman H. W. van Goor, Harry van Veldhuisen, Dirk J. van Gilst, Wiek H. de Boer, Rudolf A. |
author_facet | Ruifrok, Willem-Peter T. Qian, Cheng Silljé, Herman H. W. van Goor, Harry van Veldhuisen, Dirk J. van Gilst, Wiek H. de Boer, Rudolf A. |
author_sort | Ruifrok, Willem-Peter T. |
collection | PubMed |
description | Heart failure (HF)-associated anemia is common and has a poor outcome. Because bone marrow (BM) dysfunction may contribute to HF-associated anemia, we first investigated mechanisms of BM dysfunction in an established model of HF, the transgenic REN2 rat, which is characterized by severe hypertrophy and ventricular dilatation and SD rats as controls. Secondly, we investigated whether stimulation of hematopoiesis with erythropoietin (EPO) could restore anemia and BM dysfunction. After sacrifice, erythropoietic precursors (BFU-E) were isolated from the BM and cultured for 10 days. BFU-E were quantified and transcript abundance of genes involved in erythropoiesis were assayed. Number of BFU-E were severely decreased in BM of REN2 rats compared to SD rats (50 ± 6.2 vs. 6.4 ± 1.7, p < 0.01). EPO treatment increased hematocrit in the SD-EPO group (after 6 weeks, 49 ± 1 vs. 58 ± 1%, p < 0.01); however, in the mildly anemic REN2 rats, there was no effect (43 ± 1 vs. 44 ± 1%). This was paralleled by a 67% decrease in BFU-E in BM of REN2 rats compared to SD (p < 0.01). EPO significantly improved BFU-E in both SD and REN2 but could not restore this to control levels in the REN2 rats. Expression of several genes involved in differentiation (LMO2), mobilization (SDF-1), and iron incorporation (transferrin receptor) of the BM were differentially expressed in REN2 rats compared to SD rats, and EPO did not normalize this. Altogether, these results suggest that BM dysfunction is an important contributor to HF-associated anemia and that EPO is not an effective agent to treat HF-associated anemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-010-0710-6) contains supplementary material, which is available to authorized users. |
format | Text |
id | pubmed-3056002 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Springer-Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-30560022011-04-05 Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin Ruifrok, Willem-Peter T. Qian, Cheng Silljé, Herman H. W. van Goor, Harry van Veldhuisen, Dirk J. van Gilst, Wiek H. de Boer, Rudolf A. J Mol Med (Berl) Original Article Heart failure (HF)-associated anemia is common and has a poor outcome. Because bone marrow (BM) dysfunction may contribute to HF-associated anemia, we first investigated mechanisms of BM dysfunction in an established model of HF, the transgenic REN2 rat, which is characterized by severe hypertrophy and ventricular dilatation and SD rats as controls. Secondly, we investigated whether stimulation of hematopoiesis with erythropoietin (EPO) could restore anemia and BM dysfunction. After sacrifice, erythropoietic precursors (BFU-E) were isolated from the BM and cultured for 10 days. BFU-E were quantified and transcript abundance of genes involved in erythropoiesis were assayed. Number of BFU-E were severely decreased in BM of REN2 rats compared to SD rats (50 ± 6.2 vs. 6.4 ± 1.7, p < 0.01). EPO treatment increased hematocrit in the SD-EPO group (after 6 weeks, 49 ± 1 vs. 58 ± 1%, p < 0.01); however, in the mildly anemic REN2 rats, there was no effect (43 ± 1 vs. 44 ± 1%). This was paralleled by a 67% decrease in BFU-E in BM of REN2 rats compared to SD (p < 0.01). EPO significantly improved BFU-E in both SD and REN2 but could not restore this to control levels in the REN2 rats. Expression of several genes involved in differentiation (LMO2), mobilization (SDF-1), and iron incorporation (transferrin receptor) of the BM were differentially expressed in REN2 rats compared to SD rats, and EPO did not normalize this. Altogether, these results suggest that BM dysfunction is an important contributor to HF-associated anemia and that EPO is not an effective agent to treat HF-associated anemia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-010-0710-6) contains supplementary material, which is available to authorized users. Springer-Verlag 2010-12-30 2011 /pmc/articles/PMC3056002/ /pubmed/21191566 http://dx.doi.org/10.1007/s00109-010-0710-6 Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Original Article Ruifrok, Willem-Peter T. Qian, Cheng Silljé, Herman H. W. van Goor, Harry van Veldhuisen, Dirk J. van Gilst, Wiek H. de Boer, Rudolf A. Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
title | Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
title_full | Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
title_fullStr | Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
title_full_unstemmed | Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
title_short | Heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
title_sort | heart failure-associated anemia: bone marrow dysfunction and response to erythropoietin |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056002/ https://www.ncbi.nlm.nih.gov/pubmed/21191566 http://dx.doi.org/10.1007/s00109-010-0710-6 |
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