Beneficial effect of simvastatin on human umbilical vein endothelial cells gap junctions induced by TNF-α

Xiwen Ling; Siyuan Peng; Yaqin Xu; Fujiang Chu

doi:10.1080/19768354.2021.2023037

Beneficial effect of simvastatin on human umbilical vein endothelial cells gap junctions induced by TNF-α

Anim Cells Syst (Seoul). 2022 Jan 16;26(1):10-18. doi: 10.1080/19768354.2021.2023037. eCollection 2022.

Authors

Xiwen Ling^{1

2}, Siyuan Peng^{1

2}, Yaqin Xu^{1

2}, Fujiang Chu^{1

2}

Affiliations

¹ School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.
² Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.

Abstract

Although simvastatin has been shown to inhibit vascular permeability, which might be amplified via gap junction intercellular communication (GJIC), the underlying mechanism of action remains unclear. In the present study, we investigated the effects and mechanisms of simvastatin on endothelial cells GJIC. Specifically, human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α (10 ng/mL) alone or in combination with simvastatin (5 µM), and their effects on vascular endothelial cell GJIC tested via the scrape loading/dye transfer (SL/DT) assay. Next, we performed immunofluorescence, real-time PCR and western blot assays to analyze expression of Cx37, Cx40 and Cx43 in HUVECs. Results showed that GJIC activity in HUVECs was markedly elevated in HUVECs treated with TNF-α in combination with simvastatin. In addition, simvastatin treatment significantly upregulated expression of Cx37 and Cx40 but downregulated Cx43 mRNAs and proteins. Taken together, these marked changes indicated that simvastatin exerts its regulatory effects on gap junction function by upregulating Cx37 and Cx40 and downregulating Cx43 expression.

Keywords: Connexin proteins; HUVECs; gap junctions; mechanism; simvastatin.

Grants and funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81373960 and 81573600); Science and Technology Planning Project of Guangdong Province, China under [grant no. 2014A020212416]; and Guangzhou Science and Technology Plan Project, China under [grant no. 201707010132].