Abstract
The functional mechanisms involved in angiogenesis and the potential role of endoglin (ENG), recently described as a new marker for this process, have not been explored in Myelodysplastic Syndromes (MDS). In order to gain insight in MDS angiogenesis a combined analysis in bone marrow (BM) of gene expression levels, angiogenesis-related soluble factors and functional angiogenesis-related studies was carried out. Ninety-seven MDS patients and forty-two normal BM samples were studied. The morphology of the capillary-like structures originated by two endothelial cells lines in the BM environment of patients with refractory cytopenia with multilineage dysplasia (RCMD) was different from those of the remaining MDS. In addition, the BM mononuclear cells from RCMD patients displayed over-expression of VEGF, HIF and FN1 while they showed reduced expression of ENG in contrast to the normal ENG expression of the remaining low-risk MDS and the high expression of ENG in high-risk MDS subtype. Moreover, higher soluble ENG and soluble FLT-1 levels in BM microenvironment were observed in RCMD cases, which distinguished them from other individuals. Therefore, the present study suggests that the patterns of angiogenesis are different between the MDS subtypes. The differences in angiogenesis observed in RCMD patients could be related to ENG abnormalities.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anemia, Refractory / metabolism
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Anemia, Refractory / pathology
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Angiogenesis Inducing Agents / metabolism
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Bone Marrow / metabolism
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Bone Marrow / pathology
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Cell Lineage
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Cell Proliferation
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Cellular Microenvironment
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Endoglin
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Endothelial Cells / metabolism*
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Endothelial Cells / pathology
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Humans
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Myelodysplastic Syndromes / metabolism
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Myelodysplastic Syndromes / pathology*
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / pathology*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Solubility
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Vascular Endothelial Growth Factor A / genetics
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Angiogenesis Inducing Agents
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Antigens, CD
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ENG protein, human
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Endoglin
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Receptors, Cell Surface
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Vascular Endothelial Growth Factor A
Grants and funding
This work was partially supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543; Proyectos de Investigación del SACYL 355/A/09, COST Action “EuGESMA” (BM0801), Obra Social Banca Cívica (Caja Burgos) and by the “Acción Transversal del Cáncer” project, through an agreement between the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation, and the Cancer Research Foundation of Salamanca University and the Redes de Investigación RTICC (FIS). This work was also supported by grants from the Junta de Castilla y León (SA052A06 and SA029A09 to ARB.) and Ministerio de Ciencia e Innovación (SAF2010-15881 to JMLN). MDR is fully supported by an “Ayuda Predoctoral” by the Sociedad Española de Hematología y Hemoterapia. The Renal and Cardiovascular Physiology Unit is an Excellence Research Group awarded by Junta de Castilla y León. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.