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Functional impairment of hematopoietic progenitor cells in patients with coronary heart disease
Authors:Liguori Antonio  Fiorito Carmela  Balestrieri Maria Luisa  Crimi Ettore  Bruzzese Giuseppe  Williams-Ignarro Sharon  D'Amora Maurizio  Sommese Linda  Grimaldi Vincenzo  Minucci Pellegrino Biagio  Giovane Alfonso  Farzati Bartolomeo  Ignarro Louis J  Napoli Claudio
Institution:Department of Cardiology-CCU, Hospital of Pellegrini-ASL NA1, Naples, Italy;;Department of General Pathology, Division of Clinical Pathology and Excellence Research Center on Cardiovascular Diseases, University of Naples, Naples, Italy;;IRCCS-Multimedica, Milan, Italy;;Department of Biochemistry and Biophysics, University of Naples, Naples, Italy;;Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA;;Division of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA;;Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
Abstract:The circulating form of endothelial progenitors cells (EPCs) are derived from bone marrow (BM)-derived hematopoietic stem cells (HSCs). Enhanced mobilization of EPCs was shown to be linked to cardiac diseases. This study investigated whether reduced EPC levels in advanced coronary heart disease (CHD) are secondary to a functional exhaustion of HSCs in the BM or to reduced mobilization. Number and functional properties of EPCs were assessed in 15 healthy controls, and 40 patients with CHD. The colony-forming unit (CFU) capacity of BM-derived mononuclear cells and the CD34+ HSC number were examined in four healthy volunteers, and 15 CHD patients. EPC number was reduced in CHD patients (P < 0.01 vs. controls). Moreover, the migratory capacity was significantly impaired in EPCs of CHD patients (P < 0.05 vs. controls). On multivariate analysis, CHD was an independent predictor of functional EPC impairment. CFUs were reduced in CHD patients (59.6 +/- 21.2 vs. 75.4 +/- 25.8 in controls, P < 0.05). CHD was also predictor of impaired CFU capacity. In this small clinical study, CHD is associated with selective impairment of HSC function in the BM and in the peripheral blood, which may contribute to impairment of cardiac function.
Keywords:coronary heart disease  progenitor cells  stem cells
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