Activating TRPV1 by evodiamine attenuates atherosclerosis by inhibiting endothelial microparticle release

Endothelial microparticles (EMPs) were known as the biomarker of endothelial dysfunction, which could initiate atherosclerosis(AS). The traditional chinese medicine Evodiae and its main alkaloid component, evodiamine, exerts anti-atherosclerosis effects through transient receptor potential vanilloid type 1(TRPV1). However, it is unclear whether the anti-atherosclerosis effect of evodiamine is related to the generation of EMPs. The present study aims to investigate the anti-atherosclerosis effect of evodiamine and the underlying mechanism of the formation and release of EMPs. To establish the AS mice model, apoE^-/- mice were fed a high-fat diet for eight weeks. Histopathology results were evaluated using hematoxylin and eosin staining. The quantity of EMPs was examined by flow cytometry. Serum lipid and cytokines levels were assessed by ELISA kits, and protein expression was determined by Western blotting. We found that evodiamine decreased the plasma EMPs levels, reduced the lipid levels, IL-6 and ET-1 levels, and reduced the size of atherosclerotic lesions in apoE^-/- mice significantly. Moreover, evodiamine significantly down-regulated the expression levels of ROCK, which was involved in the release of EMPs. In contrast, pre-treatment with capsazepine (the blocker of TRPV1) abrogated these effects of evodiamine. In vitro, lipopolysaccharide was used to induce the release of EMPs in the human aortic endothelial cells(HAECs). Consistently silencing the expression of TRPV1 in the cells through siRNA interference resulted in an elevation of EMPs levels and the expression of ROCK. In conclusion, activating TRPV1 by evodiamine may inhibit the activation of ROCK and then decrease the release of EMPs, relieve the inflammation of the endothelial cells, and finally attenuate the development of atherosclerosis.

Atherosclerosis; Endothelial microparticles; Evodiamine; ROCK; Transient receptor potential vanilloid type 1.