Endothelial Progenitor Cells—Potential New Avenues to Improve Neoangiogenesis and Reendothelialization - International Review of Cell and Molecular Biology - page 66

Akt protein kinase in EPCs was observed, enhancing proliferative and
migratory activities and cell survival. An in vitro study explored the effect
of atorvastatin on ECFC. It was found that statins inhibited the senescence
of ECFC independent of nitric oxide (NO) and Rho kinase but dependent
on geranylgeranylpyrophosphate. Additionally, atorvastatin induced ECFC
proliferation in vitro ( Assmus et al., 2003 ).
Since a positive effect on neoangiogenesis is postulated to be related to
higher levels of EPC, the treatment of cardiovascular patients with statins
was conclusive, which was performed in several studies ( Leone et al., 2008;
Llevadot et al., 2001; Spadaccio et al., 2010; Tousoulis et al., 2008 ). Except
for a higher EPC count, no improved clinical results were found. While statin
treatment mobilizes EPCs, the dose-dependent effects of a continuous statin
therapy on EPCs in patients with CAD were studied in a prospective analysis
( Hristov et al., 2007 ). The initiation of statin therapy significantly diminished
the number of circulating and isolated EPCs after 3 months. Therefore, a con-
tinuous treatment with statins leads to lower amounts of CEPC.
Furthermore, these effects are not the same with all statins; for example,
Rosuvastatine did not show an effect on EPC mobilization ( Mohammad
et al., 2010 ). In conclusion, atorvastatin and simvastatin raise the amount
of CEPC in the short term, but this effect is not sustainable for longer than
a month and the effect of high CEPC counts cannot be found in an
improved clinical outcome.
4.2. Other drugs
Research on other drug interactions with EPC is growing, especially since
EPCs seem to be involved in manifold physiological and pathological pro-
cesses. Since the variety of drugs studied is so broad, this article concentrates
on a small amount of drugs as examples. The inhibition of EPC functions is
one of the main targets of these drugs, although the mechanisms of action
differ strongly.
A study by Huang et al. (2012) concentrated on the effect of Celastrol, a
traditional Chinese medicine plant, derived from Trypterygium wilfordii
Hook F. The antitumorigenic properties of Celastrol were studied. Celastrol
attenuated VEGF secretion in BM-EPC in vitro , which inhibited as well the
in vitro VEGF-induced cell viability, cell-cell adhesion, cell-ECM adhesion,
migration response, and vascular tube formation of BM-EPC. Another
study revealed that Phloroglucinol specifically inhibited VEGF-dependent
migration and capillary-like tube formation of EPC. Further, it significantly