title: Atorvastatin treatment improves endothelial function through endothelial progenitor cells mobilization in ischemic heart failure patients.
abstract: OBJECTIVE
  Endothelial function is an independent predictor of prognosis in heart failure (HF) subjects. Statins, beyond their lipid lowering role, exert beneficial effect in patients with atherosclerosis. In the present study we examined the impact of low and intermediate dose atorvastatin treatment on endothelial function, bone marrow-derived endothelial progenitor cells (EPC) mobilization and inflammatory status according to HF patient status.
  
  
  METHODS
  We studied the effect of 4 weeks administration of atorvastatin in 26 patients with ischemic HF. The study was carried out on two separate arms, one with atorvastatin 40 mg/d and one with atorvastatin 10 mg/d (randomized, double-blind, cross-over design). The number of circulating CD34(+)/CD133(+)/KDR(+) EPCs was evaluated by flow cytometry. Endothelial function was evaluated by flow mediated dilation (FMD) in the brachial artery. Serum levels of tumor necrosis factor alpha (TNF-α) were measured by ELISA.
  
  
  RESULTS
  Treatment with atorvastatin 40 mg/d significantly increased circulating EPC (p = 0.002), FMD (p = 0.001) and reduced TNF-α (p = 0.01) compared to baseline. Similarly, treatment with atorvastatin 10 mg/day increased circulating EPC (p = 0.01), FMD (p = 0.08) and reduced TNF-α (p = 0.01) compared to baseline. Interestingly, with 40 mg/day atorvastatin treatment the increase in EPC was higher in subjects categorized as NYHA class II compared to subjects categorized as NYHA class III (p = 0.03).
  
  
  CONCLUSIONS
  Our results confirmed the distinct impact of atorvastatin treatment on the restoration of endothelial function due to EPC mobilization in ischemic HF subjects. Moreover, these findings provide the potential clinical significance of EPC status monitoring to individualize treatment in HF subjects.
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Oikonomou
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece; Department of Biological Chemistry, University of Athens Medical School, Athens, Greece. Electronic address: gsiasos@med.uoa.gr.
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Siasos
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Zaromitidou
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Hatzis
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mourouzis
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Christine
authors.initials: C
authors.lastname: Chrysohoou
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Zisimos
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Savvas
authors.initials: S
authors.lastname: Mazaris
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tourikis
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Athanasiou
authors.affiliation: Department of Medicine, Division of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Christodoulos
authors.initials: C
authors.lastname: Stefanadis
authors.affiliation: Department of Biological Chemistry, University of Athens Medical School, Athens, Greece.
authors.forename: Athanasios G
authors.initials: AG
authors.lastname: Papavassiliou
authors.affiliation: 1st Cardiology Department, University of Athens Medical School, "Hippokration" Hospital, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tousoulis
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D066026:Endothelial Progenitor Cells / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006115:Greece; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications* / Q000175:diagnosis; D010455:Peptides / Q000097:blood; D011758:Pyrroles / Q000627:therapeutic use*; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; C000606023:PROM1 protein, human; D010455:Peptides; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Endothelial function; Endothelial progenitor cells; Endothelium; Heart failure; Statins