Vascular repair and anti‑inflammatory effects of soluble epoxide hydrolase inhibitor

Dai,Na; Zhao,Cuifen; Kong,Qingyu; Li,Dong; Cai,Zhifeng; Wang,Minmin

doi:10.3892/etm.2019.7396

Vascular repair and anti‑inflammatory effects of soluble epoxide hydrolase inhibitor

Authors:
- Na Dai
- Cuifen Zhao
- Qingyu Kong
- Dong Li
- Zhifeng Cai
- Minmin Wang
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Affiliations: Department of Pediatrics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China
Published online on: March 13, 2019 https://doi.org/10.3892/etm.2019.7396
Pages: 3580-3588
Copyright: © Dai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Kawasaki disease (KD) is the leading cause of acquired heart disease in pediatric patients in developed countries. Coronary artery aneurysms and myocardial infarction may occur if the disease remains untreated. An estimated 10‑20% of KD patients do not respond to intravenous gamma globulin (IVIG), and thus, alternative treatments are currently being investigated. Epoxyeicosatrienoic acids (EETs) are natural anti‑inflammatory factors and angiogenic mediators degraded by soluble epoxide hydrolase (sEH). sEH inhibitory factors have been demonstrated to stabilize EET levels, inhibit inflammation and promote vascular repair in vivo. The present study aimed to determine whether an increase in EET levels induced by treatment with the sEH inhibitor 12‑(3‑adamantan‑1‑yl‑ureido)‑dodecanoic acid (AUDA) promotes vascular repair in human coronary arterial endothelial cells (HCAECs) and reduces inflammation in a mouse model of KD induced by Lactobacillus casei cell wall extract. The effect of AUDA on vascular repair in HCAECs was assessed by using cell proliferation, migration, adhesion and tube formation assays, and the anti‑inflammatory effect of AUDA in the mouse model of KD was determined by detecting the expression of matrix metalloproteinase (MMP)‑9, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β at the protein level via ELISA. The results demonstrated that AUDA increased the proliferation, migration, adhesion and tube formation ability of HCAECs in a dose‑dependent manner. Furthermore, in the mouse model of KD, AUDA reduced the protein expression of MMP‑9, IL‑1β and TNF‑α, indicating that AUDA may alleviate inflammatory reactions in the coronary arteries of KD model mice. The present results also indicate that these effects may be exerted through the peroxisome proliferator activated receptor γ signaling pathway. Taken together, the present study supports the potential utility of AUDA in the treatment of KD.

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