Ischemia-related changes in circulating stem and progenitor cells and associated clinical characteristics in peripheral artery disease.
The extent and clinical significance of stem and progenitor cell (SPC) increases in response to lower-extremity ischemia in people with peripheral artery disease (PAD) are unclear. We compared changes in SPC levels immediately following a treadmill exercise test between individuals with and without PAD. Among participants with PAD, we determined whether more severe PAD was associated with greater increases in SPCs following treadmill exercise-induced lower-extremity ischemia. We measured SPC levels in 25 participants with PAD and 20 without PAD before and immediately after a treadmill exercise test. Participants with PAD, compared to participants without PAD, had greater increases in CD34(+)CD45(dim) (+0.08±0.03 vs -0.06±0.04, p=0.008), CD34(+)CD45(dim)CD133(+) (+0.08±0.05 vs -0.08±0.04, p=0.014), CD34(+)CD45(dim)CD31(+) (+0.10±0.03 vs -0.07±0.04, p=0.002), and CD34(+)CD45(dim)ALDH(+) SPCs (+0.18±0.07 vs -0.05±0.08, p=0.054) measured as a percentage of all white blood cells. Among participants with PAD, those with any increases in the percent of SPCs immediately after the treadmill exercise test compared to those with no change or a decrease in SPCs had lower baseline ankle-brachial index values (0.65±0.17 vs 0.90±0.19, p=0.004) and shorter treadmill times to onset of ischemic leg symptoms (2.17±1.54 vs 5.25±3.72 minutes, p=0.012). In conclusion, treadmill exercise-induced lower-extremity ischemia is associated with acute increases in circulating SPCs among people with PAD. More severe PAD is associated with a higher prevalence of SPC increases in response to lower-extremity ischemia. Further prospective study is needed to establish the prognostic significance of ischemia-related increases in SPCs among patients with PAD.
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Rana
R
Saber
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Kiang
K
Liu
National Institute on Aging, Bethesda, MD, USA.
Luigi
L
Ferrucci
Department of Family and Preventive Medicine, University of California at San Diego, La Jolla, CA, USA.
Michael H
MH
Criqui
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Lihui
L
Zhao
Department of Health Research and Policy, Stanford University, Stanford, CA, USA.
Lu
L
Tian
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Jack M
JM
Guralnik
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Yihua
Y
Liao
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Kathryn
K
Domanchuk
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
Melina R
MR
Kibbe
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
David
D
Green
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Harris
H
Perlman
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA mdm608@northwestern.edu.
Mary M
MM
McDermott
D000368:Aged; D055109:Ankle Brachial Index; D015703:Antigens, CD / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D003430:Cross-Sectional Studies; D005080:Exercise Test; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007511:Ischemia / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D010641:Phenotype; D012720:Severity of Illness Index; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*
D015703:Antigens, CD; D015415:Biomarkers
ischemia; peripheral artery disease; stem and progenitor cells; treadmill exercise