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

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.

Application of metabolomics part II: Focus on fatty acids and their metabolites in healthy adults

“…Liu et al demonstrated that the activation of FXR in mice induced the activation of the AMPK-ACC-CPT1 pathway, a signaling pathway promoting fatty acid oxidation and achieving its lipid-lowering effect ( 8 ). Additionally, it has been established that in individuals with high-fat diet-induced type 2 diabetes, monounsaturated free fatty acids (FFAs) can serve as a predictive indicator of vascular restenosis following interventional therapy ( 9 ). Chronic diseases often occur when inflammation is persistent or has not been effectively resolved ( 10 ).…”

A Serum Biomarker Panel of exomiR-451a, exomiR-25-3p and Soluble TWEAK for Early Diagnosis of Rheumatoid Arthritis

“…In this sense, our prediction models showed that YHWAB could interact with of BH3-domain proteins, known to be related to apoptosis ( 52 ). YHWAB has been reported to bind to BAD, a BCL-2 associated agonist of cell death promoting apoptosis ( 53 ). Therefore, if YHWAB protein levels decrease due to epigenetic miRNA control in early RA subjects, apoptosis can be expected to be inhibited, an event reported in RA pathogenesis ( 51 , 54 ).…”

Silencing of FOS-like antigen 1 represses restenosis via the ERK/AP-1 pathway in type 2 diabetic mice

“… 18 Numerous genes or proteins act as important regulators of cellular processes in restenosis. 19 , 20 For instance, Feng et al 19 observed an increased 14-3-3 gene (YWHAB) in oleic acid–induced VSMCs and believed that the enhanced YWHAB may aggravate restenosis by promoting cell migration. Lv et al 20 found that Pin1 is upregulated in T2D mice (after wire-injury) tissues and in VSMCs isolated from the above mice, and the further cellular experiments demonstrated that Pin1 downregulation significantly promotes the apoptosis and inhibits metastasis of VSMCs.…”