title: The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties.
abstract: Atherosclerosis develops in an environment of endothelial injury and inflammation. Circulating endothelial progenitor cells (EPCs) are required for vascular repair and restoration of normal endothelial function. We tested the hypothesis that the nonselective cyclooxygenase (COX) inhibitor aspirin (ASA) exerts an effect on circulating EPCs.
  
  
  METHODS
  As part of a larger study evaluating the effect of aspirin dose in primary and secondary prevention, subjects (n=32) were assigned randomly to either 81 mg or 325 mg aspirin daily for two months, and circulating mononuclear cells were enumerated at the beginning of the study and after 2 months using fluorescent antibodies against CD34 and CD133 as well as based on aldehyde dehydrogenase (ALDH) activity. Brachial artery endothelial function via flow-mediated dilation (BAFMD) and light transmittance platelet aggregometry in response to physiologic agonists was also determined.
  
  
  RESULTS
  Subjects taking aspirin at the time of study entry had a lower numbers of CD133+/34+ cells compared to those not previously exposed (0.01% vs. 0.05% of MNCs, P<0.03). After 2 months, subjects randomized to 81 vs. 325 mg of ASA had no significant differences in the median numbers of EPCs, although mean numbers trended lower in the high dose group. Patients on chronic ASA therapy continued to have lower numbers of EPCs. Similar effects were observed in CD34 and CD 133 single-positive cells, as well as ALDH(br) cells. BAFMD did not differ nor change significantly over time between aspirin dose groups. All patients had decreased ex vivo platelet aggregation in response to arachidonic acid and ADP stimulation.
  
  
  CONCLUSIONS
  Our preliminary studies suggest that aspirin exerts a time-dependent effect on circulating EPCs. Short-term exposure to differing doses of ASA had indeterminate effects on EPCs levels, suggesting that time of ASA exposure may play a more important role than dose. Determining the responsible mechanism(s) and the overall clinical relevance of these findings will require further investigation.
authors.affiliation: Department of Medicine, Division of Cardiology, Duke Clinical Research Institute, Durham, NC 27705, USA.
authors.forename: Junyang
authors.initials: J
authors.lastname: Lou
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.forename: Jason D
authors.initials: JD
authors.lastname: Allen
authors.forename: Stacie D
authors.initials: SD
authors.lastname: Adams
authors.forename: Shelley
authors.initials: S
authors.lastname: Myles
authors.forename: Aijing Z
authors.initials: AZ
authors.lastname: Starr
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Ortel
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001241:Aspirin / Q000008:administration & dosage*; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D002452:Cell Count; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000032:analysis; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D013234:Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D013997:Time Factors; D014463:Ultrasonography; D014481:United States; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D016861:Cyclooxygenase Inhibitors; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D000444:Aldehyde Dehydrogenase; D001241:Aspirin