Atorvastatin enhances endothelial adherens junctions through promoting VE-PTP gene transcription and reducing VE-cadherin-Y731 phosphorylation

作者：Huo, Zihe; Kong, Ying; Meng, Mei; Cao, Zhifei; Zhou, Quansheng^*

来源：Vascular Pharmacology, 2019, 117: 7-14.

DOI：10.1016/j.vph.2018.06.003

• VE-PTP
• Atorvastatin
• VE-cadherin
• Endothelial cells
• Adherens junction

Vascular endothelial protein tyrosine phosphatase (VE-PTP) is essential for endothelial cells (ECs) adherens junction and vascular homeostasis; however, the regulatory mechanism of VE-PTP transcription is unknown, and a drug able to promote VE-PTP expression in ECs has not yet been reported in the literature. In this study, we used human ECs as a model to explore small molecule compounds able to promote VE-PTP expression, and found that atorvastatin, a HMG-CoA reductase inhibitor widely used in the clinic to treat hypercholesterolemia-related cardiovascular diseases, strongly promoted VE-PTP transcription in ECs through activating the VE-PTP promoter and upregulating the expression of the transcription factor, specificity protein 1 (SP1). Additionally, atorvastatin markedly reduced VE-cadherin-Y731 phosphorylation induced by cigarette smoke extract and significantly enhanced stability of endothelial adherens junctions. Together, our findings reveal that atorvastatin up-regulates VE-PTP expression, increases VE-cadherin protein levels, and decreases VE-cadherin-Y731 phosphorylation to strengthen EC adherens junctions and maintain vascular cell monolayer integrity, offering a new mechanism of atorvastatin against CSE-induced disruption of vascular integrity and relevant cardio-cerebrovascular disease.

• 出版日期2019-6
• 单位苏州大学