Thromb Haemost 2009; 101(06): 1138-1146
DOI: 10.1160/TH08-11-0723
Endothelium and Vascular Development
Schattauer GmbH

Reduced levels of putative endothelial progenitor and CXCR4+ cells in coronary artery disease: Kinetics following percutaneous coronary intervention and association with clinical characteristics

Colin Gerard Egan
1   Molecular Medicine Section, Department of Neuroscience, University of Siena, Siena, Italy
2   Center for Stem Cell Research, University of Siena, Siena, Italy
,
Francesca Caporali
1   Molecular Medicine Section, Department of Neuroscience, University of Siena, Siena, Italy
2   Center for Stem Cell Research, University of Siena, Siena, Italy
,
Alda F. Huqi
3   Department of Cardiology, University of Siena, Siena, Italy
4   Cardiac and Thoracic Department, University of Pisa, Pisa, Italy
,
Maria Cristina Zito
3   Department of Cardiology, University of Siena, Siena, Italy
,
Marta Focardi
3   Department of Cardiology, University of Siena, Siena, Italy
,
Sergio Mondillo
3   Department of Cardiology, University of Siena, Siena, Italy
,
Carlo Pierli
3   Department of Cardiology, University of Siena, Siena, Italy
,
Mario Marzilli
4   Cardiac and Thoracic Department, University of Pisa, Pisa, Italy
,
Vincenzo Sorrentino
1   Molecular Medicine Section, Department of Neuroscience, University of Siena, Siena, Italy
2   Center for Stem Cell Research, University of Siena, Siena, Italy
› Author Affiliations
Financial support: This work was supported by a grant from Regione Toscana to the Center for Stem Cell Research, University of Siena.
Further Information

Publication History

Received: 06 November 2008

Accepted after major revision: 23 February 2009

Publication Date:
24 November 2017 (online)

Summary

Levels of circulating endothelial progenitor cells (EPCs) and CXCR4-positive cells are decreased in patients with coronary artery disease (CAD); however, their ability to change in response to acute vascular injury remains to be elucidated. Progenitor and CXCR4-positive cells were analysed by flow cytometry from the peripheral blood of 23 healthy controls and 23 patients with CAD, of which 13 patients underwent angiogram and 10 patients received percutaneous coronary intervention (PCI) with stent implantation. Baseline levels of progenitor and CXCR4-positive cells were substantially reduced in CAD patients compared to controls, although they were still capable of increasing in response to vascular injury. Levels of progenitor and CXCR4-positive cells were increased to a greater extent in the PCI group compared to angiogram patients. At presentation, levels of putative endothelial progenitor and CXCR4-positive cells were found to be negatively correlated with disease severity. A one-year follow-up revealed that out of the cell populations examined, only levels of CXCR4-positive cells were positively correlated with angina frequency in the PCI group, but not in patients receiving angiogram. Baseline levels of progenitor cells are differentially increased depending upon the severity of vascular injury incurred, regardless of a significant deficit in baseline levels in CAD patients. Levels of putative EPCs and CXCR4-positive cells were negatively correlated with disease severity at presentation, however, only CXCR4-positive cells were associated with patient condition in a one-year follow-up.

 
  • References

  • 1 Drexler H, Hornig B. Endothelial dysfunction in human disease. J Mol Cell Cardiol 1999; 31: 51-60.
  • 2 Urbich C, Dimmeler S. Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 2004; 95: 343-353.
  • 3 Hristov M, Zernecke A, Liehn EA. et al. Regulation of endothelial progenitor cell homing after arterial injury. Thromb Haemost 2007; 98: 274-277.
  • 4 Egan CG, Lavery R, Caporali F. et al. Generalised reduction of putative endothelial progenitors and CXCR4-positive peripheral blood cells in type 2 diabetes. Diabetologia 2008; 51: 1296-1305.
  • 5 Fadini GP, Miorin M, Facco M. et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005; 45: 1449-1457.
  • 6 Ingram DA, Caplice NM, Yoder MC. Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood 2005; 106: 1525-1531.
  • 7 Case J, Mead LE, Bessler WK. et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol 2007; 35: 1109-1118.
  • 8 Charo IF, Taubman MB. Chemokines in the pathogenesis of vascular disease. Circ Res 2004; 95: 858-866.
  • 9 Kucia M, Jankowski K, Reca R. et al. CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion. J Mol Histol 2004; 35: 233-245.
  • 10 Kucia M, Ratajczak J, Ratajczak MZ. Bone marrow as a source of circulating CXCR4+ tissue-committed stem cells. Biol Cell 2005; 97: 133-146.
  • 11 Shantsila E, Watson T, Lip GY. Endothelial progenitor cells in cardiovascular disorders. J Am Coll Cardiol 2007; 49: 741-752.
  • 12 Vasa M, Fichtlscherer S, Aicher A. et al. Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 2001; 89: E1-7.
  • 13 Hill JM, Zalos G, Halcox JP. et al. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 2003; 348: 593-600.
  • 14 Schmidt-Lucke C, Rössig L, Fichtlscherer S. et al. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation 2005; 11: 2981-2987.
  • 15 Eizawa T, Ikeda U, Murakami Y. et al. Decrease in circulating endothelial progenitor cells in patients with stable coronary artery disease. Heart 2004; 90: 685-686.
  • 16 Werner N, Kosiol S, Schiegl T. et al. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 2005; 353: 999-1007.
  • 17 Chen MC, Chen CJ, Yang CH. et al. Relationship of the percentage of circulating endothelial progenitor cell to the severity of coronary artery disease. Heart Vessels 2008; 1: 47-52.
  • 18 Asahara T, Masuda H, Takahashi T. et al. Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. Circ. Res 1999; 85: 221-228.
  • 19 Banerjee S, Brilakis E, Zhang S. et al. Endothelial progenitor cell mobilization after percutaneous coronary intervention. Atherosclerosis 2006; 189: 70-75.
  • 20 Bonello L, Basire A, Sabatier F. et al. Endothelial injury induced by coronary angioplasty triggers mobilization of endothelial progenitor cells in patients with stable coronary artery disease. J Thromb Haemost 2006; 4: 979-981.
  • 21 Honold J, Lehmann R, Heeschen C. et al. Effects of granulocyte colony simulating factor on functional activities of endothelial progenitor cells in patients with chronic ischemic heart disease. Arterioscler Thromb Vasc Biol 2006; 26: 2238-2243.
  • 22 Damås JK, Waehre T, Yndestad A. et al. Stromal cell-derived factor-1alpha in unstable angina: potential antiinflammatory and matrix-stabilizing effects. Circulation 2002; 106: 36-42.
  • 23 ACC/AHA guidelines for coronary angiography.. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on Coronary Angiography). Developed in collaboration with the Society for Cardiac Angiography and Interventions. Scanlon PJ, Faxon DP, Audet AM. et al. J Am Coll Cardiol. 1999; 33: 1756-1824.
  • 24 Spertus JA, Winder JA, Dewhurst TA. et al. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol 1995; 25: 333-341.
  • 25 Grundy SM, Cleeman JI, Merz CN. et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227-239.
  • 26 Wilson PW, Castelli WP, Kannel WB. Coronary risk prediction in adults (the Framingham Heart Study). Am J Cardiol 1987; 59: 91G-94G.
  • 27 Grundy SM, Pasternak R, Greenland P. et al. Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation 1999; 100: 1481-1492.
  • 28 Venn A, Britton J. Exposure to second hand smoke and biomarkers of cardiovascular disease risk in never-smoking adults. Circ 2007; 115: 990-995.
  • 29 Massa M, Rosti V, Ferrario M. et al. Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infaction. Blood 2005; 105: 199-205.
  • 30 Gill M, Dias S, Hattori K. et al. Vascular trauma induces rapid but transient mobilization of VEGFR2+ CD133+ endothelial precursor cells. Circ Res 2001; 88: 167-174.
  • 31 Wojakowski W, Tendera M, Michalowska A. et al. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circ 2004; 110: 3213-3220.
  • 32 Fadini GP, Baesso I, Albiero M. et al. Technical notes on endothelial progenitor cells: ways to escape from the knowledge plateau. Atherosclerosis 2008; 197: 496-503.
  • 33 George J, Shmilovich H, Deutsch V. et al. Comparative analysis of methods for assessment of circulating endothelial progenitor cells. Tissue Eng 2006; 12: 1-5.
  • 34 Khan SS, Solomon MA, McCoy Jr JP. Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom 2005; 64: 1-8.
  • 35 Walter DH, Rittig K, Bahlmann FH. et al. Statin therapy accelerates re-endothelialization: a novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells. Circ 2002; 105: 3017-3024.
  • 36 Llevadot J, Murasawa S, Kureishi Y. et al. HMGCoA reductase inhibitor mobilizes bone marrow--derived endothelial progenitor cells. J Clin Invest 2001; 108: 399-405.
  • 37 Dimmeler S, Aicher A, Vasa M. et al. HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. J Clin Invest 2001; 108: 391-397.
  • 38 Hristov M, Fach C, Becker C. et al. Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment. Atherosclerosis 2007; 192: 413-420.
  • 39 Ripa RS, Wang Y, Goetze JP. et al. Circulating angiogenic cytokines and stem cells in patients with severe chronic ischemic heart disease--indicators of myocardial ischemic burden?. Int J Cardiol 2007; 120: 181-187.
  • 40 Karshovska E, Zagorac D, Zernecke A. et al. A small molecule CXCR4 antagonist inhibits neointima formation and smooth muscle progenitor cell mobilization after arterial injury. J Thromb Haemost 2008; 10: 1812-1815.
  • 41 Shiba Y, Takahashi M, Yoshioka T. et al. M-CSF accelerates neointimal formation in the early phase after vascular injury in mice: the critical role of the SDF-1-CXCR4 system. Arterioscler Thromb Vasc Biol 2007; 2: 283-289.
  • 42 Zernecke A, Schober A, Bot I. et al. SDF-1alpha/ CXCR4 axis is instrumental in neointimal hyperplasia and recruitment of smooth muscle progenitor cells. Circ Res 2005; 96: 784-791.