title: Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation.
abstract: OBJECTIVE
  We investigated whether cardiac rehabilitation participation increases circulating endothelial progenitor cells (EPCs) and benefits vasculature in patients already on stable therapy previously shown to augment EPCs and improve endothelial function.
  
  
  METHODS
  Forty-six of 50 patients with coronary artery disease completed a 36-session cardiac rehabilitation program: 45 were treated with HMG-CoA reductase inhibitor (statin) therapy > or = 1 month (average baseline low-density lipoprotein cholesterol = 81 mg/dL). Mononuclear cells isolated from blood were quantified for EPCs by flow cytometry (CD133/VEGFR-2 cells) and assayed in culture for EPC colony-forming units (CFUs). In 23 patients, EPCs were stained for annexin-V as a marker of apoptosis, and nitrite was measured in blood as an indicator of intravascular nitric oxide.
  
  
  RESULTS
  Endothelial progenitor cells increased from 35 +/- 5 to 63 +/- 10 cells/mL, and EPC-CFUs increased from 0.9 +/- 0.2 to 3.1 +/- 0.6 per well (both P < .01), but 11 patients had no increase in either measure. Those patients whose EPCs increased from baseline showed significant increases in nitrite and reduction in annexin-V staining (both P < .01) versus no change in patients without increase in EPCs. Over the course of the program, EPCs increased prior to increase in nitrite in the blood.
  
  
  CONCLUSIONS
  Cardiac rehabilitation in patients receiving stable statin therapy and with low-density lipoprotein cholesterol at goal increases EPC number, EPC survival, and endothelial differentiation potential, associated with increased nitric oxide in the blood. Although this response was observed in most patients, a significant minority showed neither EPC mobilization nor increased nitric oxide in the blood.
authors.affiliation: Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Paul
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Powell
authors.forename: Michael
authors.initials: M
authors.lastname: Thompson
authors.forename: Moshe
authors.initials: M
authors.lastname: Benjamin
authors.forename: Maria
authors.initials: M
authors.lastname: Rodrigo
authors.forename: Andrea
authors.initials: A
authors.lastname: Carlow
authors.forename: Vidhya
authors.initials: V
authors.lastname: Annavajjhala
authors.forename: Sruti
authors.initials: S
authors.lastname: Shiva
authors.forename: Andre
authors.initials: A
authors.lastname: Dejam
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Gloria
authors.initials: G
authors.lastname: Zalos
authors.forename: Beverly
authors.initials: B
authors.lastname: Press
authors.forename: Mandy
authors.initials: M
authors.lastname: Murphy
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Hill
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Csako
authors.forename: Myron A
authors.initials: MA
authors.lastname: Waclawiw
authors.forename: Richard O
authors.initials: RO
authors.lastname: Cannon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000166:cytology / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000534:rehabilitation*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D005080:Exercise Test; D005081:Exercise Therapy; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D010349:Patient Compliance; D013234:Stem Cells / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009573:Nitrites; D009569:Nitric Oxide