Surface Expression of CXCR4 on Circulating CD133progenitor Cells is Associated with Plaque Instability in Subjects with Carotid Artery Stenosis

Overview

Journal J Angiogenes Res

Publisher Biomed Central

Date 2010 Jan 15

PMID 20072672

Citations 4

Authors

Dominik Sepp

Lorena Esposito

Peter Zepper

Ilka Ott

Regina Feurer

Suwad Sadikovic

Bernhard Hemmer

Holger Poppert

Affiliations

Soon will be listed here.

Abstract

Background: Circulating progenitor cells (PCs) are considered to contribute to the remodeling of atherosclerotic plaques. Their surface receptor CXCR4 plays an important role in the recruitment of PCs to their target. This study compares the mobilization of PCs and their functional characteristics in asymptomatic subjects with stable and with unstable carotid plaques. This could provide insight into plaque remodeling and help to develop biomarkers for plaque stability.

Methods: In 31 subjects with asymptomatic carotid artery stenosis we analyzed the number of CD133+ PCs, VEGFR2+CD34+ PCs and the surface expression of CXCR4 on CD133+ PCs by flow cytometry. Subjects underwent bilateral carotid MRI in a 1.5-T scanner in order to allow the categorization of plaques, following the modified criteria of the American Heart Association.

Results: The number of CD133+ PCs and VEGFR2+CD34+ PCs showed no significant difference between subjects with stable and unstable carotid plaques. The expression of CXCR4 on CD133+ PCs was higher in subjects with unstable plaques than in subjects with stable plaques (p = 0.009).

Conclusions: This study demonstrates an association between functional characteristics of circulating CD133+ PCs and plaque stability in subjects with asymptomatic carotid artery stenosis. The higher expression of CXCR4 on CD133+ PCs suggests a difference in the recruitment of PCs to the injured tissue in subjects with unstable plaques and subjects with stable plaques. As surface expression of CXCR4 on CD133+ PCs differs in subjects with unstable and with stable plaques, CXCR4 is a promising candidate for a serological biomarker for plaque stability.

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References

Peichev M, Naiyer A, Pereira D, Zhu Z, Lane W, Williams M . Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. Blood. 2000; 95(3):952-8. View

Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H . Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res. 2001; 89(1):E1-7. DOI: 10.1161/hh1301.093953. View

Hatsukami T, Ross R, Polissar N, Yuan C . Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation. 2000; 102(9):959-64. DOI: 10.1161/01.cir.102.9.959. View

Moreno P, Purushothaman K, Fuster V, Echeverri D, Truszczynska H, Sharma S . Plaque neovascularization is increased in ruptured atherosclerotic lesions of human aorta: implications for plaque vulnerability. Circulation. 2004; 110(14):2032-8. DOI: 10.1161/01.CIR.0000143233.87854.23. View

Moulton K, Vakili K, Zurakowski D, Soliman M, Butterfield C, Sylvin E . Inhibition of plaque neovascularization reduces macrophage accumulation and progression of advanced atherosclerosis. Proc Natl Acad Sci U S A. 2003; 100(8):4736-41. PMC: 153625. DOI: 10.1073/pnas.0730843100. View

Urbich C, Heeschen C, Aicher A, Dernbach E, Zeiher A, Dimmeler S . Relevance of monocytic features for neovascularization capacity of circulating endothelial progenitor cells. Circulation. 2003; 108(20):2511-6. DOI: 10.1161/01.CIR.0000096483.29777.50. View

Yuan C, Mitsumori L, Ferguson M, Polissar N, Echelard D, Ortiz G . In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques. Circulation. 2001; 104(17):2051-6. DOI: 10.1161/hc4201.097839. View

Carr S, Farb A, Pearce W, Virmani R, Yao J . Atherosclerotic plaque rupture in symptomatic carotid artery stenosis. J Vasc Surg. 1996; 23(5):755-65; discussion 765-6. DOI: 10.1016/s0741-5214(96)70237-9. View

STARY H, Chandler A, Glagov S, Guyton J, INSULL Jr W, Rosenfeld M . A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1994; 89(5):2462-78. DOI: 10.1161/01.cir.89.5.2462. View

10.

Sabeti S, Exner M, Mlekusch W, Amighi J, Quehenberger P, Rumpold H . Prognostic impact of fibrinogen in carotid atherosclerosis: nonspecific indicator of inflammation or independent predictor of disease progression?. Stroke. 2005; 36(7):1400-4. DOI: 10.1161/01.STR.0000169931.96670.fc. View

11.

Ceradini D, Kulkarni A, Callaghan M, Tepper O, Bastidas N, Kleinman M . Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10(8):858-64. DOI: 10.1038/nm1075. View

12.

Hattori K, Heissig B, Tashiro K, Honjo T, Tateno M, Shieh J . Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells. Blood. 2001; 97(11):3354-60. DOI: 10.1182/blood.v97.11.3354. View

13.

Virmani R, Kolodgie F, Burke A, Finn A, Gold H, Tulenko T . Atherosclerotic plaque progression and vulnerability to rupture: angiogenesis as a source of intraplaque hemorrhage. Arterioscler Thromb Vasc Biol. 2005; 25(10):2054-61. DOI: 10.1161/01.ATV.0000178991.71605.18. View

14.

. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. JAMA. 1995; 273(18):1421-8. View

15.

Takahashi T, Kalka C, Masuda H, Chen D, Silver M, Kearney M . Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization. Nat Med. 1999; 5(4):434-8. DOI: 10.1038/7434. View

16.

Schmid I, Krall W, Uittenbogaart C, Braun J, Giorgi J . Dead cell discrimination with 7-amino-actinomycin D in combination with dual color immunofluorescence in single laser flow cytometry. Cytometry. 1992; 13(2):204-8. DOI: 10.1002/cyto.990130216. View

17.

Mofidi R, Crotty T, McCarthy P, Sheehan S, Mehigan D, Keaveny T . Association between plaque instability, angiogenesis and symptomatic carotid occlusive disease. Br J Surg. 2001; 88(7):945-50. DOI: 10.1046/j.0007-1323.2001.01823.x. View

18.

Hill J, Zalos G, Halcox J, Schenke W, Waclawiw M, Quyyumi A . Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003; 348(7):593-600. DOI: 10.1056/NEJMoa022287. View

19.

Shintani S, Murohara T, Ikeda H, Ueno T, Honma T, Katoh A . Mobilization of endothelial progenitor cells in patients with acute myocardial infarction. Circulation. 2001; 103(23):2776-9. DOI: 10.1161/hc2301.092122. View

20.

Stein A, Wessling G, Deisenhofer I, Busch G, Steppich B, Estner H . Systemic inflammatory changes after pulmonary vein radiofrequency ablation do not alter stem cell mobilization. Europace. 2008; 10(4):444-9. DOI: 10.1093/europace/eun041. View