title: Pre-procedural atorvastatin mobilizes endothelial progenitor cells: clues to the salutary effects of statins on healing of stented human arteries.
abstract: OBJECTIVE
  Recent clinical trials suggest an LDL-independent superiority of intensive statin therapy in reducing target vessel revascularization and peri-procedural myocardial infarctions in patients who undergo percutaneous coronary interventions (PCI). While animal studies demonstrate that statins mobilize endothelial progenitor cells (EPCs) which can enhance arterial repair and attenuate neointimal formation, the precise explanation for the clinical PCI benefits of high dose statin therapy remain elusive. Thus we serially assessed patients undergoing PCI to test the hypothesis that high dose Atorvastatin therapy initiated prior to PCI mobilizes EPCs that may be capable of enhancing arterial repair.
  
  
  RESULTS
  Statin naïve male patients undergoing angiography for stent placement were randomized to standard therapy without Atorvastatin (n = 10) or treatment with Atorvastatin 80 mg (n = 10) beginning three days prior to stent implantation. EPCs were defined by flow cytometry (e.g., surface marker profile of CD45dim/34+/133+/117+). As well, we also enumerated cultured angiogenic cells (CACs) by standard in vitro culture assay. While EPC levels did not fluctuate over time for the patients free of Atorvastatin, there was a 3.5-fold increase in EPC levels with high dose Atorvastatin beginning within 3 days of the first dose (and immediately pre-PCI) which persisted at 4 and 24 hours post-PCI (p<0.05). There was a similar rise in CAC levels as assessed by in vitro culture. CACs cultured in the presence of Atorvastatin failed to show augmented survival or VEGF secretion but displayed a 2-fold increase in adhesion to stent struts (p<0.05).
  
  
  CONCLUSIONS
  High dose Atorvastatin therapy pre-PCI improves EPC number and CAC number and function in humans which may in part explain the benefit in clinical outcomes seen in patients undergoing coronary interventions.
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Hibbert
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
authors.forename: Ali
authors.initials: A
authors.lastname: Pourdjabbar
authors.forename: Trevor
authors.initials: T
authors.lastname: Simard
authors.forename: Katey
authors.initials: K
authors.lastname: Rayner
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Sun
authors.forename: Yong-Xiang
authors.initials: YX
authors.lastname: Chen
authors.forename: Lionel
authors.initials: L
authors.lastname: Filion
authors.forename: Edward R
authors.initials: ER
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000924:Anticholesteremic Agents; D001158:Arteries; D000069059:Atorvastatin; D002448:Cell Adhesion; D042783:Endothelial Cells; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000494:pharmacology*; D012038:Regeneration; D013234:Stem Cells; D015607:Stents; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin