Key Points
- To determine whether the HMG-CoA reductase inhibitor simvastatin stimulates the mobilization of bone marrow-derived endothelial progenitor cells (EPCs) and elucidate the signaling pathways involved.
- Assessed bone marrow mononuclear cell chemotaxis in vitro and quantified circulating EPCs from peripheral blood in simvastatin-treated animals.
- Evaluated bone marrow EPC incorporation into neovascularization using mice transplanted with marrow from transgenic donors expressing beta-galactosidase under the endothelial Tie-2 promoter.
- Investigated the Akt protein kinase pathway in EPC bioactivity and survival using dominant-negative Akt overexpression.
- Simvastatin increased the circulating pool of bone marrow-derived EPCs in peripheral blood and enhanced their incorporation into foci of neovascularization.
- Simvastatin rapidly activated Akt protein kinase in EPCs, significantly promoting EPC proliferation, migration, and cell survival.
- Functional inhibition via dominant-negative Akt overexpression completely blocked statin-induced EPC bioactivity.
Structured PICO
PPopulationIn vitro bone marrow mononuclear cells and in vivo animal models (mice transplanted with bone marrow from transgenic donors expressing beta-galactosidase transcriptionally regulated by the endothelial cell-specific Tie-2 promoter)
IInterventionSimvastatin (HMG-CoA reductase inhibitor)
OOutcomeMobilization of circulating endothelial progenitor cells (EPCs) and enhancement of neovascularizationsurrogate
Simvastatin promotes the mobilization of bone marrow-derived endothelial progenitor cells and enhances neovascularization through Akt signaling, revealing a novel pleiotropic effect of statins.