Endothelial progenitor cell mobilization and increased intravascular nitric oxide in patients undergoing cardiac rehabilitation.
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.
Paul
Jonathan D
JD
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Powell
Tiffany M
TM
Thompson
Michael
M
Benjamin
Moshe
M
Rodrigo
Maria
M
Carlow
Andrea
A
Annavajjhala
Vidhya
V
Shiva
Sruti
S
Dejam
Andre
A
Gladwin
Mark T
MT
McCoy
J Philip
JP
Zalos
Gloria
G
Press
Beverly
B
Murphy
Mandy
M
Hill
Jonathan M
JM
Csako
Gyorgy
G
Waclawiw
Myron A
MA
Cannon
Richard O
RO
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
D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009573:Nitrites; D009569:Nitric Oxide