Repair effect of the poly (D,L-lactic acid) nanoparticle containing tauroursodeoxycholic acid-eluting stents on endothelial injury after stent implantation

Jiedong Zhou; Jingfan Weng; Xingxiao Huang; Shimin Sun; Qi Yang; Hui Lin; Jinjin Yang; Hangyuan Guo; Jufang Chi

doi:10.3389/fcvm.2022.1025558

Repair effect of the poly (D,L-lactic acid) nanoparticle containing tauroursodeoxycholic acid-eluting stents on endothelial injury after stent implantation

Front Cardiovasc Med. 2022 Nov 8:9:1025558. doi: 10.3389/fcvm.2022.1025558. eCollection 2022.

Authors

Jiedong Zhou¹, Jingfan Weng², Xingxiao Huang¹, Shimin Sun¹, Qi Yang¹, Hui Lin¹, Jinjin Yang¹, Hangyuan Guo³, Jufang Chi¹

Affiliations

¹ Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.
² Zhejiang Hospital Affiliated to Medical College of Zhejiang University, Hangzhou, China.
³ Shaoxing University School of Medicine, Shaoxing, China.

Abstract

Background: Chronic endoplasmic reticulum stress (ERS) plays a crucial role in cardiovascular diseases. Thus, it can be considered a therapeutic target for these diseases. In this study, poly (D,L-lactic acid) (PDLLA) nanoparticle-eluting stents loaded with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, was fabricated to assess their ability to reduce endothelial cell apoptosis and promote re-endothelialization after stent implantation.

Materials and methods: PDLLA nanoparticles loaded with TUDCA were prepared via the emulsification-solvent evaporation method. The cumulative release rates of TUDCA were measured in vitro via high-performance liquid chromatography. The carotid arteries of rabbits were subsequently implanted with stents in vivo. The rabbits were then sacrificed after 4 weeks for scanning electron microscopy. Meanwhile, TUDCA concentration in the homogenate of the peripheral blood and distal vascular tissue after stent implantation was measured. The effect of TUDCA on ERS, apoptosis, and human umbilical vein endothelial cell (HUVEC) function was investigated in vitro by performing cell migration assay, wound healing assay, cell proliferation assays, endoplasmic reticulum (ER)-specific fluorescence staining, immunofluorescence, and western blotting.

Results: TUDCA nanoparticles were released slowly over 28 days. In addition, TUDCA-eluting stents enhanced re-endothelialization and accelerated the recovery of endotheliocytes in vivo. ERS and apoptosis significantly increased in H₂O₂-treated HUVECs in vitro. Meanwhile, TUDCA reduced apoptosis and improved function by inhibiting ERS in H₂O₂-treated HUVECs. Decreased rates of apoptosis and ERS were observed after silencing XBP-1s in H₂O₂-treated HUVECs.

Conclusion: TUDCA can inhibit apoptosis and promote re-endothelialization after stent implantation by inhibiting IRE/XBP1s-related ERS. These results indicate the potential therapeutic application of TUDCA as a drug-coated stent.

Keywords: ERS; PDLLA nanoparticle-eluting stent; TUDCA; apoptosis; re-endothelialization.