title: Endothelial progenitor cells in diabetic patients with myocardial infarction - can statins improve their function?
abstract: The effect of statins on endothelial progenitor cells (EPCs) function derived from diabetic patients (DMpts) with acute myocardial infarction (AMI) is unknown. In this study we assess the response of early and late EPCs from diabetic versus non-diabetic patients (NDMpts) with AMI to statins. EPCs were obtained from 10 diabetic and 10 age-matched non-diabetic male patients with AMI. For each patient, cultures of early and late EPCs were performed under 4 different conditions: normal glucose concentration (control); high glucose concentration; normal glucose concentration with atorvastatin supplementation and normal glucose concentration with pravastatin supplementation. To compare the effect of these treatments on EPC function in DMpts versus NDMpts, we performed in vitro: EPC colony-forming units (CFU) assay; cell cycle analysis; viability assessment and expression of the surface markers CXCR4, CD133, CD34 and KDR. Under control conditions, CFU numbers were reduced in DMpts-derived EPCs when compared to those of NDMpts (1.4±0.8 vs 2.6±1.2 CFU/well, P=0.021). When early EPCs from DMpts were cultured in the presence of statins, CFU capacity was restored, surmounting that of NDMpts under control conditions. Statins significantly improved viability of early EPCs and delayed the onset of late EPCs senescence, even in cells from DMpts. In addition, statins induced approximately a 2-fold increase in the proportion of late EPCs in S-phase of the cell cycle (P<0.05). Statins have a beneficial effect on both early and late EPCs from DMpts with AMI. Despite the functional impairment of EPCs from DMpts, they exhibit similar responsiveness to statins as equivalent cells from NDMpts.
authors: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal; Cardiology Department, University Hospital Center of Coimbra, Portugal. Electronic address: natalia.antonio@gmail.com.
authors: Natália
authors: N
authors: António
authors: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal; Center of Ophthalmology and Vision Sciences, Institute for Biomedical Imaging and Life Science, Faculty of Medicine, University of Coimbra, Portugal.
authors: Ana
authors: A
authors: Soares
authors: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal; Center of Ophthalmology and Vision Sciences, Institute for Biomedical Imaging and Life Science, Faculty of Medicine, University of Coimbra, Portugal.
authors: Rosa
authors: R
authors: Fernandes
authors: Cardiology Department, University Hospital Center of Coimbra, Portugal.
authors: Francisco
authors: F
authors: Soares
authors: Blood and Transplantation Center of Coimbra, Portuguese Institute of Blood and Transplantation, Coimbra, Portugal.
authors: Ana
authors: A
authors: Lopes
authors: Blood and Transplantation Center of Coimbra, Portuguese Institute of Blood and Transplantation, Coimbra, Portugal.
authors: Tiago
authors: T
authors: Carvalheiro
authors: Blood and Transplantation Center of Coimbra, Portuguese Institute of Blood and Transplantation, Coimbra, Portugal.
authors: Artur
authors: A
authors: Paiva
authors: Cardiology Department, University Hospital Center of Coimbra, Portugal.
authors: Luís A
authors: LA
authors: Providência
authors: Cardiology Department, University Hospital Center of Coimbra, Portugal.
authors: Lino
authors: L
authors: Gonçalves
authors: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Portugal.
authors: Carlos
authors: C
authors: Fontes Ribeiro
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: Diabetes mellitus; Endothelial progenitor cells; Function; Myocardial infarction; Statins