Human exercise-induced circulating progenitor cell mobilization is nitric oxide-dependent and is blunted in South Asian men.
OBJECTIVE
Circulating progenitor cells (CPC) have emerged as potential mediators of vascular repair. In experimental models, CPC mobilization is critically dependent on nitric oxide (NO). South Asian ethnicity is associated with reduced CPC. We assessed CPC mobilization in response to exercise in Asian men and examined the role of NO in CPC mobilization per se.


RESULTS
In 15 healthy, white European men and 15 matched South Asian men, CPC mobilization was assessed during moderate-intensity exercise. Brachial artery flow-mediated vasodilatation was used to assess NO bioavailability. To determine the role of NO in CPC mobilization, identical exercise studies were performed during intravenous separate infusions of saline, the NO synthase inhibitor L-NMMA, and norepinephrine. Flow-mediated vasodilatation (5.8%+/-0.4% vs 7.9%+/-0.5%; P=0.002) and CPC mobilization (CD34(+)/KDR(+) 53.2% vs 85.4%; P=0.001; CD133(+)/CD34(+)/KDR(+) 48.4% vs 73.9%; P=0.05; and CD34(+)/CD45(-) 49.3% vs 78.4; P=0.006) was blunted in the South Asian group. CPC mobilization correlated with flow-mediated vasodilatation and l-NMMA significantly reduced exercise-induced CPC mobilization (CD34(+)/KDR(+) -3.3% vs 68.4%; CD133(+)/CD34(+)/KDR(+) 0.7% vs 71.4%; and CD34(+)/CD45(-) -30.5% vs 77.8%; all P<0.001).


CONCLUSIONS
In humans, NO is critical for CPC mobilization in response to exercise. Reduced NO bioavailability may contribute to imbalance between vascular damage and repair mechanisms in South Asian men.
Cubbon
Richard M
RM
Division of Cardiovascular and Diabetes Research, Leeds Multidisciplinary Cardiovascular Research Centre, LIGHT Laboratories, Clarendon Way, The University of Leeds, Leeds, LS2 9JT, United Kingdom.
Murgatroyd
Scott R
SR
Ferguson
Carrie
C
Bowen
T Scott
TS
Rakobowchuk
Mark
M
Baliga
Vivek
V
Cannon
Daniel
D
Rajwani
Adil
A
Abbas
Afroze
A
Kahn
Matthew
M
Birch
Karen M
KM
Porter
Karen E
KE
Wheatcroft
Stephen B
SB
Rossiter
Harry B
HB
Kearney
Mark T
MT
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D044466:Asian People; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000503:physiopathology; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015444:Exercise; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000008:administration & dosage; D010455:Peptides / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014664:Vasodilation; D044465:White People; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D004791:Enzyme Inhibitors; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D040301:Vascular Endothelial Growth Factor Receptor-2; D009638:Norepinephrine