European Journal of Applied Physiology

, Volume 119, Issue 3, pp 743–752 | Cite as

Circulating angiogenic cell response to sprint interval and continuous exercise

  • Louis O’Carroll
  • Bruce Wardrop
  • Ronan P. Murphy
  • Mark D. Ross
  • Michael HarrisonEmail author
Original Article



Although commonly understood as immune cells, certain T lymphocyte and monocyte subsets have angiogenic potential, contributing to blood vessel growth and repair. These cells are highly exercise responsive and may contribute to the cardiovascular benefits seen with exercise.


To compare the effects of a single bout of continuous (CONTEX) and sprint interval exercise (SPRINT) on circulating angiogenic cells (CAC) in healthy recreationally active adults.


Twelve participants (aged 29 ± 2 years, BMI 25.5 ± 0.9 kg m− 2, \(\dot {V}{{\text{O}}_2}\)peak 44.3 ± 1.8 ml kg− 1 min− 1; mean ± SEM) participated in the study. Participants completed a 45-min bout of CONTEX at 70% peak oxygen uptake and 6 × 20 s sprints on a cycle ergometer, in a counterbalanced design. Blood was sampled pre-, post-, 2 h and 24 h post-exercise for quantification of CAC subsets by whole blood flow cytometric analysis. Angiogenic T lymphocytes (TANG) and angiogenic Tie2-expressing monocytes (TEM) were identified by the expression of CD31 and Tie2, respectively.


Circulating (cells µL− 1) CD3+CD31+ TANG increased immediately post-exercise in both trials (p < 0.05), with a significantly greater increase (p < 0.05) following SPRINT (+ 57%) compared to CONTEX (+ 14%). Exercise increased (p < 0.05) the expression of the chemokine receptor CXCR4 on TANG at 24 h. Tie2-expressing classical (CD14++CD16), intermediate (CD14++CD16+) and non-classical (CD14+CD16++) monocytes and circulating CD34+CD45dim progenitor cells were higher post-exercise in SPRINT, but unchanged in CONTEX. All post-exercise increases in SPRINT were back to pre-exercise levels at 2 h and 24 h.


Acute exercise transiently increases circulating TANG, TEM and progenitor cells with greater increases evident following very high intensity sprint exercise than following prolonged continuous paced endurance exercise.


Angiogenic T cells Tie2 expressing monocytes Endothelial progenitor cells High intensity exercise 



This study was supported by Technological Sector Research Strand I funding to Waterford Institute of Technology.

Author contributions

MH, MDR and RM conceived and designed the research. LOC and BW conducted the experiments. LOC, BW, MDR and MH analysed the data. MH and LOC wrote the initial manuscript draft. All authors contributed to amendments and approved the manuscript.


  1. Asahara T, Murohara T, Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967CrossRefGoogle Scholar
  2. Caligiuri G, Rossignol P, Julia P, Groyer E, Mouradian D, Urbain D, Misra N, Ollivier V, Sapoval M, Boutouyrie P, Kaveri SV, Nicoletti A, Lafont A (2006) Reduced immunoregulatory CD31 + T cells in patients with atherosclerotic abdominal aortic aneurysm. Arterioscler Thromb Vasc Biol 26:618–623. CrossRefGoogle Scholar
  3. Capoccia BJ, Shepherd RM, Link DC (2006) G-CSF and AMD3100 mobilize monocytes into the blood that stimulate angiogenesis in vivo through a paracrine mechanism. Blood 108:2438–2445. CrossRefGoogle Scholar
  4. Chang E, Paterno J, Duscher D, Maan ZN, Chen JS, Januszyk M, Rodrigues M, Rennert RC, Bishop S, Whitmore AJ, Whittam AJ, Longaker MT, Gurtner GC (2015) Exercise induces stromal cell-derived factor-1alpha-mediated release of endothelial progenitor cells with increased vasculogenic function. Plast Reconstr Surg 135:340e–350. eCrossRefGoogle Scholar
  5. Cocks M, Shaw CS, Shepherd SO, Fisher JP, Ranasinghe AM, Barker TA, Tipton KD, Wagenmakers AJ (2013) Sprint interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males. J Physiol 591:641–656. CrossRefGoogle Scholar
  6. De Palma M, Murdoch C, Venneri MA, Naldini L, Lewis CE (2007) Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications. Trends Immunol 28:519–524. CrossRefGoogle Scholar
  7. De Biase C, De Rosa R, Luciano R, De Luca S, Capuano E, Trimarco B, Galasso G (2013) Effects of physical activity on endothelial progenitor cells (EPCs). Front Physiol 4:414. Google Scholar
  8. Dimitrov S, Lange T, Born J (2010) Selective mobilization of cytotoxic leukocytes by epinephrine. J Immunol 184:503–511. CrossRefGoogle Scholar
  9. Dopheide JF, Geissler P, Rubrech J, Trumpp A, Zeller GC, Daiber A, Munzel T, Radsak MP, Espinola-Klein C (2016) Influence of exercise training on proangiogenic TIE-2 monocytes and circulating angiogenic cells in patients with peripheral arterial disease. Clin Res Cardiol 105:666–676. CrossRefGoogle Scholar
  10. Gibala MJ, Little JP, Macdonald MJ, Hawley JA (2012) Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol 590:1077–1084. CrossRefGoogle Scholar
  11. Graff RM, Kunz HE, Agha NH, Baker FL, Laughlin M, Bigley AB, Markofski MM, LaVoy EC, Katsanis E, Bond RA, Bollard CM, Simpson RJ (2018) Beta2-Adrenergic receptor signaling mediates the preferential mobilization of differentiated subsets of CD8 + T-cells, NK-cells and non-classical monocytes in response to acute exercise in humans. Brain Behav Immun Google Scholar
  12. Hur J, Yang HM, Yoon CH, Lee CS, Park KW, Kim JH, Kim TY, Kim JY, Kang HJ, Chae IH, Oh BH, Park YB, Kim HS (2007) Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies. Circulation 116:1671–1682. CrossRefGoogle Scholar
  13. Jaipersad AS, Shantsila A, Lip GY, Shantsila E (2014) Expression of monocyte subsets and angiogenic markers in relation to carotid plaque neovascularization in patients with pre-existing coronary artery disease and carotid stenosis. Ann Med 46:530–538. CrossRefGoogle Scholar
  14. Jensen L, Bangsbo J, Hellsten Y (2004) Effect of high intensity training on capillarization and presence of angiogenic factors in human skeletal muscle. J Physiol 557:571–582. CrossRefGoogle Scholar
  15. Kruger K, Lechtermann A, Fobker M, Volker K, Mooren FC (2008) Exercise-induced redistribution of T lymphocytes is regulated by adrenergic mechanisms. Brain Behav Immun 22:324–338. CrossRefGoogle Scholar
  16. Kruger K, Alack K, Ringseis R, Mink L, Pfeifer E, Schinle M, Gindler K, Kimmelmann L, Walscheid R, Muders K, Frech T, Eder K, Mooren FC (2016) Apoptosis of T-cell subsets after acute high-intensity interval exercise. Med Sci Sports Exerc 48:2021–2029. CrossRefGoogle Scholar
  17. Kushner EJ, MacEneaney OJ, Morgan RG, Van Engelenburg AM, Van Guilder GP, DeSouza CA (2010a) CD31 + T cells represent a functionally distinct vascular T cell phenotype. Blood Cells Mol Dis 44:74–78. CrossRefGoogle Scholar
  18. Kushner EJ, Weil BR, MacEneaney OJ, Morgan RG, Mestek ML, Van Guilder GP, Diehl KJ, Stauffer BL, DeSouza CA (2010b) Human aging and CD31 + T-cell number, migration, apoptotic susceptibility, and telomere length. J Appl Physiol (1985) 109:1756–1761 CrossRefGoogle Scholar
  19. Lansford KA, Shill DD, Dicks AB, Marshburn MP, Southern WM, Jenkins NT (2016) Effect of acute exercise on circulating angiogenic cell and microparticle populations. Exp Physiol 101:155–167. CrossRefGoogle Scholar
  20. Mao L, Huang M, Chen SC, Li YN, Xia YP, He QW, Wang MD, Huang Y, Zheng L, Hu B (2014) Endogenous endothelial progenitor cells participate in neovascularization via CXCR4/SDF-1 axis and improve outcome after stroke. CNS Neurosci Ther 20:460–468. CrossRefGoogle Scholar
  21. Milanovic Z, Sporis G, Weston M (2015) Effectiveness of high-intensity interval training (HIT) and continuous endurance training for VO2max Improvements: a systematic review and meta-analysis of controlled trials. Sports Med 45:1469–1481. CrossRefGoogle Scholar
  22. Murias JM, Kowalchuk JM, Ritchie D, Hepple RT, Doherty TJ, Paterson DH (2011) Adaptations in capillarization and citrate synthase activity in response to endurance training in older and young men. J Gerontol A Biol Sci Med Sci 66:957–964. CrossRefGoogle Scholar
  23. Okutsu M, Ishii K, Niu KJ, Nagatomi R (2005) Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress. Am J Physiol Regul Integr Comp Physiol 288:R591–R599. CrossRefGoogle Scholar
  24. Okutsu M, Suzuki K, Ishijima T, Peake J, Higuchi M (2008) The effects of acute exercise-induced cortisol on CCR2 expression on human monocytes. Brain Behav Immun 22:1066–1071. CrossRefGoogle Scholar
  25. Patel AS, Smith A, Nucera S, Biziato D, Saha P, Attia RQ et al (2013) TIE2-expressing monocytes/macrophages regulate revascularization of the ischemic limb. EMBO Mol Med 5:858–869. CrossRefGoogle Scholar
  26. Ross MD, Wekesa AL, Phelan JP, Harrison M (2014) Resistance exercise increases endothelial progenitor cells and angiogenic factors. Med Sci Sports Exerc 46:16–23. CrossRefGoogle Scholar
  27. Ross M, Tormey P, Ingram L, Simpson R, Malone E, Florida-James G (2016) A 10 km time trial running bout acutely increases the number of angiogenic T cells in the peripheral blood compartment of healthy males. Exp Physiol 101:1253–1264. CrossRefGoogle Scholar
  28. Ross M, Ingram L, Taylor G, Malone E, Simpson RJ, West D, Florida-James G (2018a) Older men display elevated levels of senescence-associated exercise-responsive CD28(null) angiogenic T cells compared with younger men. Physiol Rep 6:e13697. CrossRefGoogle Scholar
  29. Ross MD, Malone EM, Simpson R, Cranston I, Ingram L, Wright GP, Chambers G, Florida-James G (2018b) Lower resting and exercise-induced circulating angiogenic progenitors and angiogenic T cells in older men. Am J Physiol Heart Circ Physiol 314:H392–H402. CrossRefGoogle Scholar
  30. Rouhl RP, Mertens AE, van Oostenbrugge RJ, Damoiseaux JG, Debrus-Palmans LL, Henskens LH, Kroon AA, de Leeuw PW, Lodder J, Tervaert JW (2012) Angiogenic T-cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease. Stroke 43:256–258. CrossRefGoogle Scholar
  31. Sawyer BJ, Tucker WJ, Bhammar DM, Ryder JR, Sweazea KL, Gaesser GA (2016) Effects of high-intensity interval training and moderate-intensity continuous training on endothelial function and cardiometabolic risk markers in obese adults. J Appl Physiol (1985) 121:279–288. CrossRefGoogle Scholar
  32. Shantsila E, Wrigley B, Tapp L, Apostolakis S, Montoro-Garcia S, Drayson MT, Lip GY (2011) Immunophenotypic characterization of human monocyte subsets: possible implications for cardiovascular disease pathophysiology. J Thromb Haemost 9:1056–1066. CrossRefGoogle Scholar
  33. Shill DD, Marshburn MP, Hempel HK, Lansford KA, Jenkins NT (2016) Heterogeneous circulating angiogenic cell responses to acute maximal exercise. Med Sci Sports Exerc 48:2536–2543. CrossRefGoogle Scholar
  34. Simpson RJ, Florida-James GD, Cosgrove C, Whyte GP, Macrae S, Pircher H, Guy K (2007) High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects. J Appl Physiol (1985) 103:396–401. CrossRefGoogle Scholar
  35. Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I (1996) The ISHAGE guidelines for CD34 + cell determination by flow cytometry. International Society of Hematotherapy Graft Engineering. J Hematother 5:213–226. CrossRefGoogle Scholar
  36. Tsai HH, Lin CP, Lin YH, Hsu CC, Wang JS (2016) High-intensity Interval training enhances mobilization/functionality of endothelial progenitor cells and depressed shedding of vascular endothelial cells undergoing hypoxia. Eur J Appl Physiol 116(11–12):2375–2388. CrossRefGoogle Scholar
  37. Van Craenenbroeck AH, Van Ackeren K, Hoymans VY, Roeykens J, Verpooten GA, Vrints CJ, Couttenye MM, Van Craenenbroeck EM (2014) Acute exercise-induced response of monocyte subtypes in chronic heart and renal failure. Mediators Inflamm 2014:216534. Google Scholar
  38. Weber C, Shantsila E, Hristov M, Caligiuri G, Guzik T, Heine GH et al (2016) Role and analysis of monocyte subsets in cardiovascular disease. Joint consensus document of the European Society of Cardiology (ESC) Working Groups “Atherosclerosis & Vascular Biology” and “Thrombosis”. Thromb Haemost 116:626–637. CrossRefGoogle Scholar
  39. Weil BR, Kushner EJ, Diehl KJ, Greiner JJ, Stauffer BL, Desouza CA (2011) CD31 + T cells, endothelial function and cardiovascular risk. Heart Lung Circ 20:659–662. CrossRefGoogle Scholar
  40. Witkowski S, Jenkins NT, Hagberg JM (2011) Enhancing treatment for cardiovascular disease: exercise and circulating angiogenic cells. Exerc Sport Sci Rev 39:93–101. CrossRefGoogle Scholar
  41. Yoder MC, Mead LE, Prater D, Krier TR, Mroueh KN, Li F, Krasich R, Temm CJ, Prchal JT, Ingram DA (2007) Redefining endothelial progenitor cells via clonal analysis hematopoietic stem/progenitor cell principals. Blood 109:1801–1809. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Louis O’Carroll
    • 1
  • Bruce Wardrop
    • 1
  • Ronan P. Murphy
    • 2
  • Mark D. Ross
    • 3
  • Michael Harrison
    • 1
    Email author
  1. 1.Department of Sport and Exercise ScienceWaterford Institute of TechnologyWaterfordIreland
  2. 2.School of Health and Human PerformanceDublin City UniversityDublinIreland
  3. 3.School of Applied SciencesEdinburgh Napier UniversityEdinburghUK

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