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- W3093572010 abstract "Imatinib, a PDGF receptor tyrosine kinase inhibitor, has been shown to suppress intimal hyperplasia in different animal models under normal metabolic milieu, diabetic, and/or hypercholesterolemic conditions. However, the impact of imatinib treatment on injury-induced neointimal hyperplasia has not yet been investigated in the setting of insulin resistance without frank diabetes. Using a mouse model of high fat diet (HFD)-induced insulin resistance and guidewire-induced arterial injury, the present study demonstrates that intraperitoneal administration of imatinib (25 mg/kg/day) for ~3 weeks resulted in a marked attenuation of neointimal hyperplasia (intima/media ratio) by ~78% (n = 6-9 per group; P < 0.05). Imatinib treatment also led to significant improvements in key metabolic parameters. In particular, imatinib improved insulin resistance and glucose tolerance, as revealed by complete inhibition of HFD-induced increase in HOMA-IR index and AUCIPGTT, respectively. In addition, imatinib treatment led to diminutions in HFD-induced increases in plasma total cholesterol and triglycerides by ~73% and ~59%, respectively. Furthermore, imatinib decreased HFD-induced increase in visceral fat accumulation by ~51% (as determined by epididymal white adipose tissue weight). Importantly, imatinib treatment in HFD-fed mice enhanced plasma levels of high-molecular-weight adiponectin by ~2-fold without affecting total adiponectin. However, there were no significant changes in mean arterial pressure in insulin-resistant state or after imatinib exposure, as measured by tail-cuff method. Together, the present findings suggest that targeting PDGF receptor tyrosine kinase using imatinib may provide a realistic treatment option to prevent injury-induced neointimal hyperplasia and diet-induced insulin resistance in obesity." @default.
- W3093572010 created "2020-10-29" @default.
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- W3093572010 date "2021-01-01" @default.
- W3093572010 modified "2023-09-27" @default.
- W3093572010 title "Imatinib improves insulin resistance and inhibits injury-induced neointimal hyperplasia in high fat diet-fed mice" @default.
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- W3093572010 doi "https://doi.org/10.1016/j.ejphar.2020.173666" @default.
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