title: Mobilization of endothelial progenitor cells in acute cardiovascular events in the PROCELL study: time-course after acute myocardial infarction and stroke.
abstract: The mobilization pattern and functionality of endothelial progenitor cells after an acute ischemic event remain largely unknown. The aim of our study was to characterize and compare the short- and long-term mobilization of endothelial progenitor cells and circulating endothelial cells after acute myocardial infarction or atherothrombotic stroke, and to determine the relationship between these cell counts and plasma concentrations of vascular cell adhesion molecule (VCAM-1) and Von Willebrand factor (VWF) as surrogate markers of endothelial damage and inflammation. In addition, we assessed whether endothelial progenitor cells behave like functional endothelial cells. We included 150 patients with acute myocardial infarction or atherothrombotic stroke and 145 controls. Endothelial progenitor cells [CD45-, CD34+, KDR+, CD133+], circulating endothelial cells [CD45-, CD146+, CD31+], VWF, and VCAM-1 levels were measured in controls (baseline only) and in patients within 24h (baseline) and at 7, 30, and 180 days after the event. Myocardial infarction patients had higher counts of endothelial progenitor cells and circulating endothelial cells than the controls (201.0/mL vs. 57.0/mL; p<0.01 and 181.0/mL vs. 62.0/mL; p<0.01). Endothelial progenitor cells peaked at 30 days post-infarction (201.0/mL vs. 369.5/mL; p<0.01), as did VCAM-1 (573.7 ng/mL vs. 701.8 ng/mL; p<0.01). At 180 days post-infarction, circulating endothelial cells and VWF decreased, compared to baseline. In stroke patients, the number of endothelial progenitor cells - but not circulating endothelial cells - was higher than in controls (90.0/mL vs. 37.0/mL; p=0.01; 105.0/mL vs. 71.0/mL; p=0.11). At 30 days after stroke, however, VCAM-1 peaked (628.1/mL vs. 869.1/mL; p<0.01) but there was no significant change in endothelial progenitor cells (90/mL vs. 78/mL; p<0.34). At 180 days after stroke, circulating endothelial cells and VWF decreased, compared to baseline. Cultured endothelial progenitor cells from controls and myocardial infarction patients had endothelial phenotype characteristics and exhibited functional differences in adhesion and Ca(2+) influx, but not in proliferation and vasculogenesis. In myocardial infarction patients, VCAM-1 levels and mobilization of endothelial progenitor cells peaked at 30 days after the ischemic event. Although a similar VCAM-1 kinetic was observed in stroke patients, endothelial progenitor cells did not increase. Endothelial progenitor cells had mature endothelial capabilities in vitro.
authors.affiliation: Cardiology Department, Thorax Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain. Electronic address: aregueir@clinic.ub.es.
authors.forename: Ander
authors.initials: A
authors.lastname: Regueiro
authors.affiliation: Neurology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), DCEXS Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cuadrado-Godia
authors.affiliation: INCLIVA Biomedical Research Institute, Hospital Clínico de Valencia, Department of Physiology, Universitat de València, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueno-Betí
authors.affiliation: Hemotherapy-Hemostasis Department, Biomedical Diagnostics Center CDB, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Maribel
authors.initials: M
authors.lastname: Diaz-Ricart
authors.affiliation: Nephrology Department, Hospital del Mar, Universitat Autònoma de Barcelona, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Oliveras
authors.affiliation: INCLIVA Biomedical Research Institute, Hospital Clínico de Valencia, Department of Physiology, Universitat de València, Valencia, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Novella
authors.affiliation: Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Gemma González
authors.initials: GG
authors.lastname: Gené
authors.affiliation: Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Carole
authors.initials: C
authors.lastname: Jung
authors.affiliation: Epidemiology and Cardiovascular Genetic Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Subirana
authors.affiliation: Cardiology Department, Thorax Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jose Tomás
authors.initials: JT
authors.lastname: Ortiz-Pérez
authors.affiliation: Cardiology Department, Thorax Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Roqué
authors.affiliation: Cardiology Department, Thorax Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Freixa
authors.affiliation: Cardiology Department, Hospital Clínico Universitario, School of Medicine, Universitat de València, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Núñez
authors.affiliation: Hemotherapy-Hemostasis Department, Biomedical Diagnostics Center CDB, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Gines
authors.initials: G
authors.lastname: Escolar
authors.affiliation: Epidemiology and Cardiovascular Genetic Group, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Marrugat
authors.affiliation: INCLIVA Biomedical Research Institute, Hospital Clínico de Valencia, Department of Physiology, Universitat de València, Valencia, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Hermenegildo
authors.affiliation: Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Valverde
authors.affiliation: Neurology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), DCEXS Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Roquer
authors.affiliation: Cardiology Department, Hospital Clínico Universitario, School of Medicine, Universitat de València, Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sanchis
authors.affiliation: Cardiology Department, Thorax Institute, Hospital Clínic, IDIBAPS, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Magda
authors.initials: M
authors.lastname: Heras
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002452:Cell Count; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D010641:Phenotype; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor
keywords: Cell-adhesion molecule; Endothelial progenitor cell; Myocardial infarction; Stroke