Upregulated 14‑3‑3β aggravates restenosis by promoting cell migration following vascular injury in diabetic rats with elevated levels of free fatty acids

Feng,Lishuai; Dou,Chaoran; Wang,Jianbo; Jiang,Chunyu; Ma,Xu; Liu,Jingjing

doi:10.3892/ijmm.2018.3671

Upregulated 14‑3‑3β aggravates restenosis by promoting cell migration following vascular injury in diabetic rats with elevated levels of free fatty acids

Authors:
- Lishuai Feng
- Chaoran Dou
- Jianbo Wang
- Chunyu Jiang
- Xu Ma
- Jingjing Liu
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Affiliations: Department of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China, Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: May 11, 2018 https://doi.org/10.3892/ijmm.2018.3671
Pages: 1074-1085

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Abstract

Mono‑unsaturated free fatty acids (FFAs) can serve as a predictive indicator of vascular restenosis following interventional therapy, particularly in individuals with high‑fat diet‑induced type 2 diabetes. However, the pathogenic mechanism remains to be fully elucidated. In the present study, the levels of tyrosine 3‑monooxygenase/tryptophan 5‑monooxygenase activation protein β (YWHAB; also known as 14‑3‑3β), in vascular smooth muscle cells (VSMCs) treated with different concentrations of oleic acid (OA) were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. The migration of VSMCs was examined using wound‑healing and Transwell migration assays. The protein distribution of B‑cell lymphoma 2 (BCL‑2)‑associated death promoter (BAD) in VSMCs treated with OA was examined by immunofluorescence and western blot analyses. In in vivo experiments, the carotid artery morphology of rats in different groups was assessed at 14 days post‑injury by non-invasive ultrasonographic imaging and confirmed by histological staining. The expression of YWHAB was upregulated by OA in a concentration‑dependent manner in VSMCs. In the in vivo experiments, carotid stenosis was more serious among high‑FFA diabetic rats. However, silencing of YWHAB significantly alleviated carotid neointimal hyperplasia among the diabetic rats with elevated FFA levels. In addition, YWHAB silencing alleviated the migration of OA‑treated VSMCs and increased translocation of the BAD protein from the cytoplasm to the mitochondria. In conclusion, the results showed that FFA‑induced upregulation of YWHAB was involved in neointimal hyperplasia by enhancing the migration of VSMCs following carotid artery injury. The inhibition of YWHAB may serve as a novel potential pharmacological target for preventing vascular restenosis following interventional therapy in diabetic individuals with high FFA levels.

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