Emodin as a selective proliferative inhibitor of vascular smooth muscle cells versus endothelial cells suppress arterial intima formation.

A well-known natural anthraquinone "Emodin", has been proven to inhibit the proliferation of vascular smooth muscle cells (VSMCs). But the anti-proliferative effects of emodin on both VSMCs versus vascular endothelial cells (VECs) are still largely unknown. Herein, a comparative study for the evaluation of anti-proliferation effects of emodin on human VSMCs and VECs was designed. Various methodologies including MTS, EdU assay, FACS analysis, qRT-PCR and mitochondrial fluorescent probes were used for detecting cell viabilities, DNA synthesis rate, cell cycle, proliferation genes expression levels and mitochondrial activities, respectively. In addition, carotid arteries balloon injury was performed to evaluate the effects of emodin on intima hyperplasia (IH) and re-endothelialization. The emodin showed a dose-dependent (0.05 to 5 μM) inhibition of hVSMCs proliferation was quiet higher than hVECs in vitro. Conditioned culture media with a range of emodin concentrations (2.5, and 5 μM) reduced CDK1, Ki67, and E2F-1 gene expression, along with inhibition of mitochondrial activities in both hVSMCs and hVECs cells, while former remained highly sensitive. Emodin (10 mg/kg) was injected intraperitoneally for 2 weeks, and had obvious alleviation in an endothelial denudation induced-IH formation and limited interfere-endothelialization in injured arteries in vivo. Emodin preferentially inhibited hVSMCs proliferation but not the hVECs in vitro and had limited influence on the re-endothelialization of later in a rat artery endothelial denudation model. It is concluded that emodin will provide a promising approach for efficient prevention of blood vessel restenosis.