Rosuvastatin inhibits high glucose-stimulated upregulation of VCAM-1 via the MAPK-signalling pathway in endothelial cells

Abstract

Objective: The aim of this study is to investigate the molecular mechanisms and effect of rosuvastatin on adhesion molecule induction in human endothelial cells under high-glucose conditions (HG).

Methods and results: The effects of rosuvastatin on vascular cell adhesion molecule (VCAM)-1 production and pERK phosphorylation were measured in HG-induced human umbilical vein endothelial cells (HUVECs) with inhibitors targeting the mitogen-activated protein kinase (MAPK) signal pathway. HG increased levels of VCAM-1. Treatment with rosuvastatin inhibited VCAM-1 expression in a concentration- and time-dependent manner. In addition, we investigated the effects of rosuvastatin on the extracellular signal-regulated kinase (ERK) 1/2 signal pathway. Rosuvastatin completely inhibited HG-induced phosphorylation of ERK. ERK/MAPK inhibitors completely prevented the VCAM-1 inhibition effect of rosuvastatin under HG condition.

Conclusions: This study demonstrated that rosuvastatin suppresses HG-induced VCAM-1 production via the MAPK signalling pathway, playing a role in the suppression of atherosclerosis.

Keywords:

• Adhesion
• endothelial cells
• MAPK pathway
• rosuvastatin

Acknowledgements

This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (No. NRF-2015M3A9E6029558), (No. NRF-2016R1A2B4012683), the research fund of the Catholic Kwandong University St. Mary's Hospital (201701390001) and the Dong-A University research fund.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (No. NRF-2015M3A9E6029558), (No. NRF-2016R1A2B4012683), the research fund of the Catholic Kwandong University St. Mary’s Hospital (201604750001) and the Dong-A University research fund.