Novel TNF-α receptor 1 antagonist treatment attenuates arterial inflammation and intimal hyperplasia in Mice

Aim: tumor necrosis factor receptor 1 (tnfr1) participates importantly in arterial inflammation in genetically altered mice; however it remains undetermined whether a selective tnfr1 antagonist inhibits arterial inflammation and intimal hyperplasia. this study aimed to determine the effect and mechanism of a novel tnfr1 antagonist in the suppression of arterial inflammation. methods: we investigated intimal hyperplasia in il-1 receptor antagonist-deficient mice two weeks after inducing femoral artery injury in an external vascular cuff model. all mice received intraperitoneal injections of tnfr1 antagonist (peg-r1anttnf) or normal saline twice daily for 14 days. results: peg-r1anttnf treatment yielded no adverse systemic effects,and we observed no significant differences in serum cholesterol or blood pressure in either group; however,selective pegr1anttnf treatment significantly reduced intimal hyperplasia (19,671±4,274 vs. 11,440±3,292 μm 2; p = 0.001) and the intima/media ratio (1.86±0.43 vs. 1.34±0.36; p = 0.029),compared with saline injection. immunostaining revealed that peg-r1anttnf inhibits nuclear factor-κ b (nf-κb),suppressing smooth muscle cell (smc) proliferation and decreasing chemokine and adhesion molecule expression,and thus decreasing intimal hyperplasia and inflammation. conclusions: our data suggest that peg-r1anttnf suppresses smc proliferation and inflammation by inhibiting nf-κb. this study highlights the potential therapeutic benefit of selective tnfr1 antagonist therapy in preventing intimal hyperplasia and arterial inflammation.