Published Online
on May 9, 2005

A more recent version of this article appeared on May 24, 2005

This Article Full Text (PDF) Data Supplement All Versions of this Article: 111/20/2645    most recent CIRCULATIONAHA.104.492678v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Modarai, B. Articles by Smith, A. Search for Related Content PubMed PubMed Citation Articles by Modarai, B. Articles by Smith, A. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Stem Cells Related Collections Deep vein thrombosis Angiogenesis Animal models of human disease

Submitted on July 20, 2004
Revised on January 12, 2005
Accepted on January 20, 2005

Endothelial Progenitor Cells Are Recruited Into Resolving Venous Thrombi

B. Modarai BSc, MRCS (Ed and Eng), K. G. Burnand MS, FRCS, B. Sawyer , and A. Smith PhD^*

From the Academic Department of Surgery, Cardiovascular Division, King’s College, London, United Kingdom.

^* To whom correspondence should be addressed. E-mail: alberto.smith{at}kcl.ac.uk.

Background--The purpose of this study was to determine whether endothelial cells of bone marrow origin are involved in thrombus recanalization.

Methods and Results--Irradiated mice were reconstituted with bone marrow from transgenic donors expressing green fluorescent protein (GFP) linked to the Tie2 promoter. Thrombi were formed in 2 groups of 6 mice. GFP-expressing cells were located and quantified in sections of the thrombi taken after 7 and 14 days. The cell markers Mac-3, F4/80, CD68 (macrophage), and vascular endothelial growth factor receptor 2 (VEGFR2; endothelial cells) were used to determine colocalization with GFP expression in tissue sections and peritoneal macrophages. The markers CD34 and VEGFR2 were used to quantify changes in circulating endothelial cells by flow cytometry of blood from 3 cohorts of wild-type animals that had either a thrombus induced (n=18), a sham operation (n=18), or no operation (n=10). The number of GFP-expressing cells was found to increase by 3-fold in thrombi formed in transplanted animals between 7 and 14 days after induction (P=0.0022). No GFP-expressing cells were found lining the new vascular channels that formed at either time interval, but many of the GFP-expressing cells also expressed Mac-3, CD68, and VEGFR2. Approximately twice as many circulating CD34⁺/VEGFR2⁺ cells were found by day 3 in animals with thrombus compared with sham controls (CD45^-, P=0.046 and CD45⁺, P=0.016).

Conclusions--Bone marrow-derived, Tie2-expressing cells were recruited into the thrombus during resolution but did not line the new vessels. Many of these cells expressed a macrophage phenotype and may represent a population of plastic stem cells that orchestrate thrombus recanalization.

Key words: thrombus • cells • revascularization • angiogenesis

This article has been cited by other articles:

				S. Purhonen, J. Palm, D. Rossi, N. Kaskenpaa, I. Rajantie, S. Yla-Herttuala, K. Alitalo, I. L. Weissman, and P. Salven Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth PNAS, May 6, 2008; 105(18): 6620 - 6625. [Abstract] [Full Text] [PDF]

				D. Chen, J. M. Abrahams, L. M. Smith, J. H. McVey, R. I. Lechler, and A. Dorling Regenerative repair after endoluminal injury in mice with specific antagonism of protease activated receptors on CD34+ vascular progenitors Blood, April 15, 2008; 111(8): 4155 - 4164. [Abstract] [Full Text] [PDF]

				D. Bonderman, J. Jakowitsch, B. Redwan, H. Bergmeister, M.-K. Renner, H. Panzenbock, C. Adlbrecht, A. Georgopoulos, W. Klepetko, M. Kneussl, et al. Role for Staphylococci in Misguided Thrombus Resolution of Chronic Thromboembolic Pulmonary Hypertension Arterioscler. Thromb. Vasc. Biol., April 1, 2008; 28(4): 678 - 684. [Abstract] [Full Text] [PDF]

				L. Bezuidenhout, M. Bracher, G. Davison, P. Zilla, and N. Davies Ang-2 and PDGF-BB cooperatively stimulate human peripheral blood monocyte fibrinolysis J. Leukoc. Biol., June 1, 2007; 81(6): 1496 - 1503. [Abstract] [Full Text] [PDF]

				S. Nishimura, I. Manabe, M. Nagasaki, Y. Hosoya, H. Yamashita, H. Fujita, M. Ohsugi, K. Tobe, T. Kadowaki, R. Nagai, et al. Adipogenesis in Obesity Requires Close Interplay Between Differentiating Adipocytes, Stromal Cells, and Blood Vessels Diabetes, June 1, 2007; 56(6): 1517 - 1526. [Abstract] [Full Text] [PDF]

				S. Mieno, B. Ramlawi, M. Boodhwani, R. T. Clements, K. Minamimura, T. Maki, S.-H. Xu, C. Bianchi, J. Li, and F. W. Sellke Role of Stromal-Derived Factor-1{alpha} in the Induction of Circulating CD34+CXCR4+ Progenitor Cells After Cardiac Surgery. Circulation, July 4, 2006; 114(1 Suppl): 186 - 192. [Abstract] [Full Text] [PDF]