1. Circulating stem cell vary with NYHA stage in heart failure patients
- Author
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Gloria Francolini, Cinzia Fortini, Carlo Alberto Beltrami, Alessandro Fucili, Barbara Toffoletto, Elisa Puppato, Valeria Fiorelli, Daniela Cesselli, Antonio Paolo Beltrami, Natascha Bergamin, Roberto Ferrari, Cristina Morelli, and Adriana Olivares
- Subjects
Male ,Vascular Endothelial Growth Factor A ,blood/classification/pathology ,Becaplermin ,CD34 ,heart failure ,Severity of Illness Index ,CXCR4 ,Aged, Analysis of Variance, Antigens ,CD ,blood, Antigens ,Thy-1 ,blood, Chemokine CXCL12 ,blood, Cytokines ,blood, Endothelial Cells ,metabolism, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factor 2 ,blood, Heart Failure ,blood/classification/pathology, Hematopoietic Stem Cells ,metabolism, Hepatocyte Growth Factor ,blood, Humans, Male, Mesenchymal Stromal Cells ,metabolism, Middle Aged, Platelet-Derived Growth Factor ,metabolism, Proto-Oncogene Proteins c-sis, Receptors ,blood, Severity of Illness Index, Stem Cells ,metabolism, Tumor Necrosis Factor-alpha ,blood, Vascular Endothelial Growth Factor A ,blood ,Receptors ,Platelet-Derived Growth Factor ,Mesenchymal Stromal Cells ,Hepatocyte Growth Factor ,Stem Cells ,Proto-Oncogene Proteins c-sis ,Articles ,Middle Aged ,Haematopoiesis ,Molecular Medicine ,Female ,Fibroblast Growth Factor 2 ,Hepatocyte growth factor ,Stem cell ,medicine.drug ,Receptors, CXCR4 ,medicine.medical_specialty ,Enzyme-Linked Immunosorbent Assay ,Biology ,NO ,myocardial repair ,Antigens, CD ,Internal medicine ,medicine ,Humans ,CD90 ,Antigens ,Progenitor cell ,Cytokines ,Endothelial progenitor cells ,Haematopoietic stem cells ,Heart failure ,Mesenchymal stem cells ,Myocardial repair ,Aged ,endothelial progenitor cells ,Analysis of Variance ,mesenchymal stem cells ,Tumor Necrosis Factor-alpha ,Mesenchymal stem cell ,Endothelial Cells ,Cell Biology ,Hematopoietic Stem Cells ,Chemokine CXCL12 ,cytokines ,Endocrinology ,Immunology ,Thy-1 Antigens ,metabolism ,haematopoietic stem cells - Abstract
We have investigated the blood levels of sub-classes of stem cells (SCs) [mesenchymal stem cells (MSCs), haematopoietic stem cells (HSCs), endothelial progenitor cells/circulating endothelial cells (EPCs/CECs) and tissue-committed stem cells (TCSCs)] in heart failure (HF) patients at different stage of pathology and correlated it with plasmatic levels of proangiogenic cytokines. Peripheral blood level of SCs were analysed in 97 HF patients (24 in NYHA class I, 41 in class II, 17 in class III and 15 in class IV) and in 23 healthy controls. Plasmatic levels of PDGF-BB, bFGF, HGF, vascular endothelial growth factor (VEGF), SDF-1α, TNF-α and NTproBNP were also measured. Compared with healthy individuals, MSC, and in particular the sub-classes CD45(-) CD34(-) CD90(+) , CD45(-) CD34(-) CD105(+) and CD45(-) CD34(-) CXCR4(+) were significantly enhanced in NYHA class IV patients (16.8-, 6.4- and 2.7-fold, respectively). Level of CD45(-) CD34(-) CD90(+) CXCR4(+) cells progressively increased from class II to class IV (fold increases compared with controls: 8.5, 12 and 21.5, respectively). A significant involvement of CXCR4(+) subpopulation of HSC (CD45(+) CD34(+) CD90(+) CXCR4(+) , 1.4 versus 13.3 cells/μl in controls and NYHA class III patients, respectively) and TCSC (CD45(-) CD34(+) CXCR4(+) , 1.5 cells/ μl in controls versus 12.4 and 28.6 cells/μl in NYHA classes II and IV, respectively) were also observed. All tested cytokines were enhanced in HF patients. In particular, for PDGF-BB and SDF-1α we studied specific ligand/receptors pairs. Interestingly, the first one positively correlated with TCSCs expressing PDGFR (r = 0.52, P = 0.001), whereas the second one correlated with TCSCs (r = 0.34, P = 0.005) and with MSCs CD90(+) expressing CXCR4 (r = 0.39, P = 0.001). HF is characterized by the increase in the circulating levels of different MSC, HSC, EPC and TCSC subsets. Both the entity and kinetic of this process varied in distinct cell subsets. Specifically, differently from HSCs and EPCs/CECs, MSCs and TCSCs significantly increased with the progression of the disease, suggesting a possible distinct role of these cells in the pathophysiology of HF.
- Published
- 2011