The DOI matches its OpenAlex record; 42 of the 42 references it cites were found in a registry or an index.
HMG-CoA reductase inhibitor mobilizes bone marrow–derived endothelial progenitor cells
Open accessAbstract
Endothelial progenitor cells (EPCs) have been isolated from circulating mononuclear cells in peripheral blood and shown to incorporate into foci of neovascularization, consistent with postnatal vasculogenesis. These circulating EPCs are derived from bone marrow and are mobilized endogenously in response to tissue ischemia or exogenously by cytokine stimulation. We show here, using a chemotaxis assay of bone marrow mononuclear cells in vitro and EPC culture assay of peripheral blood from simvastatin-treated animals in vivo, that the HMG-CoA reductase inhibitor, simvastatin, augments the circulating population of EPCs. Direct evidence that this increased pool of circulating EPCs originates from bone marrow and may enhance neovascularization was demonstrated in simvastatin-treated mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter. The role of Akt signaling in mediating effects of statin on EPCs is suggested by the observation that simvastatin rapidly activates Akt protein kinase in EPCs, enhancing proliferative and migratory activities and cell survival. Furthermore, dominant negative Akt overexpression leads to functional blocking of EPC bioactivity. These findings establish that augmented mobilization of bone marrow-derived EPCs through stimulation of the Akt signaling pathway constitutes a novel function for HMG-CoA reductase inhibitors.
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Cites
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Self-citationStimulation of Bone Formation in Vitro and in Rodents by Statins
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Cited by
Circulating endothelial progenitor cells, vascular function, and cardiovascular risk
Hill, J. M., Zalos, G., Halcox, J. P. J., Schenke, W. H., Waclawiw, M. A., Quyyumi, A. A., & Finkel, T. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022287 · Cited by 3,423
Endothelial Progenitor Cells: Characterization and Role in Vascular Biology
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PLEIOTROPIC EFFECTS OF STATINS
Liao, J. K., & Laufs, U. (2005) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095748 · Cited by 1,994
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Ding, D.-C., Shyu, W.-C., & Lin, S.-Z. (2011) · Cell Transplantation · doi:10.3727/096368910x · Cited by 894
Metadata
- Authors
- Llevadot, J., Murasawa, S., Kureishi, Y., Uchida, S., Masuda, H., Kawamoto, A., Walsh, K., Isner, J. M., & Asahara, T.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-08-01
- Volume
- 108
- Issue
- 3
- Pages
- 399-405
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2092368086
- Cited by
- 709
- References
- 42
- FWCI
- 14.33
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Llevadot, J., Murasawa, S., Kureishi, Y., Uchida, S., Masuda, H., Kawamoto, A., Walsh, K., Isner, J. M., & Asahara, T. (2001). HMG-CoA reductase inhibitor mobilizes bone marrow–derived endothelial progenitor cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci13131
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