Arsenic trioxide activates yes-associated protein by lysophosphatidic acid metabolism to selectively induce apoptosis of vascular smooth muscle cells.

Inhibition of vascular smooth muscle cells (VSMCs) proliferation without dysregulating endothelial cells (ECs) may provide an ideal therapy for in-stent restenosis. Due to its anti-proliferation effect on VSMCs and pro-endothelium effect, arsenic trioxide (ATO) has been used in a drug-eluting stent in a recent clinical trial. However, the underlying mechanism by which ATO achieves this effect has not been determined. In the present work, we showed that ATO induced apoptosis in VSMCs but not in ECs. Mechanistically, ATO achieved this through modulation of cellular metabolism to increase lysophosphatidic acid (LPA) in VSMCs, while LPA concentration was stable in ECs. The elevated LPA facilitated the nuclear accumulation and initiated the transcriptional function of Yes-associated protein (YAP) in VSMCs. YAP regulated the transcription of N6-Methyladenosine (m6A) modulators (Mettl14 and Wtap) to increase the m6A methylation levels of apoptosis-related genes to induce their high expression and exacerbate VSMCs apoptosis. On the other hand, YAP nuclear accumulation in ECs was not observed. Collectively, our data exhibited the molecular process involved in selective apoptosis of VSMCs induced by ATO.

The biological responses and mechanisms of endothelial cells to magnesium alloy.

Due to its good biocompatibility and degradability, magnesium alloy (Mg alloy) has shown great promise in cardiovascular stent applications. Rapid stent re-endothelialization is derived from migrated and adhered endothelial cells (ECs), which is an effective way to reduce late thrombosis and inhibit hyperplasia. However, fundamental questions regarding Mg alloy affecting migration and adhesion of ECs are not fully understood. Here, we evaluated the effects of Mg alloy on the ECs proliferation, adhesion and migration. A global gene expression profiling of ECs co-culturing with Mg alloy was conducted, and the adhesion- and migration-related genes were examined. We found that Mg alloy had no adverse effects on ECs viability but significantly affected ECs migration and adhesion. Co-cultured with Mg alloy extract, ECs showed contractive adhesion morphology and decreased motility, which was supported by the down-regulation of adhesion-related genes (Paxillin and Vinculin) and migration-related genes (RAC 1, Rho A and CDC 42). Accordingly, the re-endothelialization of Mg alloy stent was inhibited in vivo. Our results may provide new inspiration for improving the broad application of Mg alloy stents.