Silymarin Inhibits Endothelial Progenitor Cellsʼ Senescence and Protects Against the Antiproliferative Activity of Rapamycin: Preliminary Study

Abstract

Rapamycin, an antiproliferative agent used on drug-eluting stents, induces endothelial progenitor cells (EPCs) senescence through telomerase inactivation and may impair the reendothelization of an injured arterial wall, leading to thrombosis. We examined whether silymarin, a complex of flavonolignans with hepatoprotective and antioxidative properties, can protect EPCs against rapamycin-induced senescence. Mononuclear cells were isolated from peripheral blood of healthy volunteers. EPCs were cultured in endothelial cell growth medium-2 in the presence or absence of rapamycin (0.1 ng/mL) and/or silymarin (12.5–50 μg/mL). EPCs senescence–associated b-galactosidase activity, telomerase activity, and prolifertive activity were measured. The influence on tubular-like structure formation in vitro was investigated, and colony-forming assay on methylcellulose plates was performed. Silymarin increased telomerase activity 3-fold, reduced the number of senescent cells, and increased EPC proliferative activity (up to 64%) in comparison with cells cultured with rapamycin alone. Moreover, silymarin partially prevented impairment of tubular-like structure formation in Matrigel by rapamycin. These findings suggest that silymarin counteracts the inhibitory effects of rapamycin in EPCs. Silymarin may protect EPCs against the antiproliferative effects of rapamycin and restore their reconstructive ability.