Astaxanthin inhibits homocysteine‑induced endothelial cell dysfunction via the regulation of the reactive oxygen species‑dependent VEGF‑VEGFR2‑FAK signaling pathway

Wang,Xian‑Jun; Tian,Da‑Chen; Wang,Feng‑Wen; Zhang,Meng‑Hao; Fan,Cun‑Dong; Chen,Wang; Wang,Mei‑Hong; Fu,Xiao‑Yan; Ma,Jin‑Kui

doi:10.3892/mmr.2019.10162

Astaxanthin inhibits homocysteine‑induced endothelial cell dysfunction via the regulation of the reactive oxygen species‑dependent VEGF‑VEGFR2‑FAK signaling pathway

Authors:
- Xian‑Jun Wang
- Da‑Chen Tian
- Feng‑Wen Wang
- Meng‑Hao Zhang
- Cun‑Dong Fan
- Wang Chen
- Mei‑Hong Wang
- Xiao‑Yan Fu
- Jin‑Kui Ma
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Affiliations: Department of Neurology, People's Hospital of Linyi Affiliated to Qingdao University, Linyi, Shandong 276000, P.R. China, Department of Biochemistry, Basic Medical School, Taishan Medical University, Taian, Shandong 271000, P.R. China, Department of Food Science and Technology, School of Food and Pharmaceutical Engineering, Zhaoqing University, Zhaoqing, Guangdong 526061, P.R. China
Published online on: April 12, 2019 https://doi.org/10.3892/mmr.2019.10162
Pages: 4753-4760
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Increased plasma levels of homocysteine (Hcy) can cause severe damage to vascular endothelial cells. Hcy‑induced endothelial cell dysfunction contributes to the occurrence and development of human cerebrovascular diseases (CVDs). Our previous studies have revealed that astaxanthin (ATX) exhibits novel cardioprotective activity against Hcy‑induced cardiotoxicity in vitro and in vivo. However, the protective effect and mechanism of ATX against Hcy‑induced endothelial cell dysfunction requires further investigation. In the present study, treatment of human umbilical vascular endothelial cells (HUVECs) with Hcy inhibited the migration, invasive and tube formation potentials of these cells in a dose‑dependent manner. Hcy treatment further induced a time‑dependent increase in the production of reactive oxygen species (ROS), and downregulated the expression of vascular endothelial growth factor (VEGF), phosphorylated (p)‑Tyr‑VEGF receptor 2 (VEGFR2) and p‑Tyr397‑focal adhesion kinase (FAK). On the contrary, ATX pre‑treatment significantly inhibited Hcy‑induced cytotoxicity and increased HUVEC migration, invasion and tube formation following Hcy treatment. The mechanism of action may involve the effective inhibition of Hcy‑induced ROS generation and the recovery of FAK phosphorylation. Collectively, our findings suggested that ATX could inhibit Hcy‑induced endothelial dysfunction by suppressing Hcy‑induced activation of the VEGF‑VEGFR2‑FAK signaling axis, which indicates the novel therapeutic potential of ATX in treating Hcy‑mediated CVD.

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