title: The atheroma plaque secretome stimulates the mobilization of endothelial progenitor cells ex vivo.
abstract: Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenerative medicine due to their assigned role in angiogenesis and vascular repair. In response to injury, EPCs promote vascular remodeling by replacement of damaged endothelial cells and/or by secreting angiogenic factors over the damaged tissue. Nevertheless, such mechanisms need to be further characterized. In the current approach we have evaluated the initial response of early EPCs (eEPCs) from healthy individuals after direct contact with the factors released by carotid arteries complicated with atherosclerotic plaques (AP), in order to understand the mechanisms underlying the neovascularization and remodeling properties assigned to these cells. Herein, we found that the AP secretome stimulated eEPCs proliferation and mobilization ex vivo, and such increase was accompanied by augmented permeability, cell contraction and also an increase of cell-cell adhesion in association with raised vinculin levels. Furthermore, a comparative mass spectrometry analysis of control versus stimulated eEPCs revealed a differential expression of proteins in the AP treated cells, mostly involved in cell migration, proliferation and vascular remodeling. Some of these protein changes were also detected in the eEPCs isolated from atherosclerotic patients compared to eEPCs from healthy donors. We have shown, for the first time, that the AP released factors activate eEPCs ex vivo by inducing their mobilization together with the expression of vasculogenic related markers. The present approach could be taken as a ex vivo model to study the initial activation of vascular cells in atherosclerosis and also to evaluate strategies looking to potentiate the mobilization of EPCs prior to clinical applications.
authors.affiliation: Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, CSIC-Universidad de Sevilla, Sevilla, Spain; Dpt. of Medical Physiology and Biophysics, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Vega
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Netherlands Proteomics Center, Utrecht, The Netherlands.
authors.forename: Violette
authors.initials: V
authors.lastname: Gautier
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Fernandez-Ponce
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Extremera
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Netherlands Proteomics Center, Utrecht, The Netherlands.
authors.forename: A F M
authors.initials: AFM
authors.lastname: Altelaar
authors.affiliation: Center for Molecular Biology Severo Ochoa, Autonoma University, Madrid, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Millan
authors.affiliation: Angiology & Vascular Surgery Unit, Virgen Macarena Hospital, Seville, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Tellez
authors.affiliation: Angiology & Vascular Surgery Unit, Virgen Macarena Hospital, Seville, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Hernandez-Campos
authors.affiliation: Angiology & Vascular Surgery Unit, Hospital Universitario Puerta del Mar, Cadiz, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Conejero
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Bolivar
authors.affiliation: Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, CSIC-Universidad de Sevilla, Sevilla, Spain; Dpt. of Medical Physiology and Biophysics, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pardal
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Garcia-Cózar
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Aguado
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Netherlands Proteomics Center, Utrecht, The Netherlands.
authors.forename: Albert J R
authors.initials: AJR
authors.lastname: Heck
authors.affiliation: Biomedicine, Biotechnology and Public Health Department, Cadiz University, Spain; Institute of Biomedical Research Cadiz (INIBICA), Spain. Electronic address: maricarmen.duran@gm.uca.es.
authors.forename: Mª Carmen
authors.initials: MC
authors.lastname: Duran-Ruiz
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D066026:Endothelial Progenitor Cells / Q000378:metabolism*; D006801:Humans; D010539:Permeability; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D020543:Proteome
keywords: Atherosclerosis; Cell migration; Cell therapy; Endothelial progenitor cells; Proteomics