Ischemia-related changes in circulating stem and progenitor cells and associated clinical characteristics in peripheral artery disease

Rana Saber, Kiang Liu, Luigi Ferrucci, Michael H. Criqui, Lihui Zhao, Lu Tian, Jack M. Guralnik, Yihua Liao, Kathryn Domanchuk, Melina R. Kibbe, David Green, Harris Perlman, Mary M. McDermott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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+CD45dim (+0.08±0.03 vs '0.06±0.04, p=0.008), CD34+CD45dimCD133+ (+0.08±0.05 vs '0.08±0.04, p=0.014), CD34+CD45dimCD31+ (+0.10±0.03 vs '0.07±0.04, p=0.002), and CD34+CD45dimALDH+ 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.

Original languageEnglish (US)
Pages (from-to)534-543
Number of pages10
JournalVascular Medicine (United Kingdom)
Volume20
Issue number6
DOIs
StatePublished - Dec 1 2015

Funding

In summary, PAD participants have significantly greater increases in SPC levels 15 minutes but not 24 hours after a treadmill exercise test compared to participants without PAD. PAD participants with increases in the percentage of SPCs after an ischemic stimulus have more severe PAD and shorter pain-free treadmill walking time. Further study is needed to establish the prognostic significance of SPC elevations following leg ischemia in participants with PAD. We should like to thank Katherine Barnes for her contribution to this work. Declaration of conflicting interest The authors declare that there is no conflict of interest. Funding The study was funded by the National Heart, Lung, and Blood Institute (R01-HL107510) and the National Institute of Health’s Intramural Program of the National Institute on Aging.

Keywords

  • ischemia
  • peripheral artery disease
  • stem and progenitor cells
  • treadmill exercise

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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