Impairment of circulating endothelial progenitors in Down syndrome
- Equal contributors
1 Institute of Genetics and Biophysics ''A. Buzzati-Traverso'', IGB-CNR, Naples, Italy
2 Section of Microbiology, Department of Experimental Medicine, 1st School of Medicine, Second University of Naples, Naples, Italy
3 Department of General Pathology and Excellence Research Center on Cardiovascular Diseases, 1st School of Medicine, Second University of Naples, Naples, Italy
4 IRCCS Fondazione SDN, Naples, Italy
5 Istituto per le Applicazioni del Calcolo, "Mauro Picone", CNR, Naples, Italy
6 Department of Biological Science, University of Naples "Federico II", Naples, Italy
7 Department of Biochemistry and Biophysics, Second University of Naples, Naples, Italy
8 IRCCS Multimedica, Milan, Italy
9 Department of Biochemistry and Medical Biotechnology, University of Naples "Federico II", Naples, Italy
10 Institute of General Pathology, Section of Clinical Pathology, Faculty of Medicine, University of Milan, Milan, Italy
11 Cardiology Department of Second University of Naples, "Monaldi Hospital", Naples, Italy
12 Department of Cellular and Molecular Biology and Pathology "L. Califano" and School of Biotechnological Sciences, University of Naples "Federico II", Naples, Italy
BMC Medical Genomics 2010, 3:40 doi:10.1186/1755-8794-3-40Published: 13 September 2010
Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.
Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.
We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.
Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.