Vorapaxar stabilizes permeability of the endothelial barrier under cholesterol stimulation via the AKT/JNK and NF‑κB signaling pathways

Pang,Jianliang; Hu,Peiyang; Wang,Junwei; Jiang,Jinsong; Lai,Jifu

doi:10.3892/mmr.2019.10211

Vorapaxar stabilizes permeability of the endothelial barrier under cholesterol stimulation via the AKT/JNK and NF‑κB signaling pathways

Authors:
- Jianliang Pang
- Peiyang Hu
- Junwei Wang
- Jinsong Jiang
- Jifu Lai
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Affiliations: Department of Vascular Surgery, Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang 317200, P.R. China, Department of Surgery, Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang 317200, P.R. China, Department of Internal Medicine, Tiantai People's Hospital of Zhejiang Province, Taizhou, Zhejiang 317200, P.R. China, Department of Vascular Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P.R. China
Published online on: April 30, 2019 https://doi.org/10.3892/mmr.2019.10211
Pages: 5291-5300
Copyright: © Pang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis (AS) is an inflammatory disease that occurs in the arterial wall and is characterized by progressive lipid accumulation within the intima of large arteries, leading to the dysfunction of endothelial cells and further destruction of the endothelial barrier and vascular tone. Arterial intima injury accelerates the adhesion and activation of platelets at the injury site. The activation of platelets results in the secretion of growth factors, leading to the migration and proliferation of vascular smooth muscle cells (VSMCs), promoting the formation of plaque, resulting in the formation of thrombus. The present study found that vorapaxar could alleviate the inflammatory response induced by a high concentration of cholesterol stimulation and increase the release of nitric oxide (NO) via the protein kinase B (AKT) signaling pathway and regulation of the intracellular concentration of Ca2+ ([Ca2+]i). We also found that vorapaxar could reduce the damage of DNA caused by cholesterol stimulation and regulate the cell cycle via the AKT/JNK signaling pathway and its downstream molecules glycogen synthase kinase 3β (GSK‑3β) and connexin 43, maintaining the integrity of the endothelial barrier and proliferation of endothelial cells, serving a protective role in endothelial cells.

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