Intimal
hyperplasia, the key event of arterial restenosis, is a result of vascular smooth muscle cell (VSMC) proliferation and migration. Previous studies have demonstrated that total Panax notoginseng
saponin (TPNS) represses intimal
hyperplasia and inhibits the proliferation of VSMCs following balloon injury. However, the underlying roles of TPNS in intimal
hyperplasia remain unclear. In this study, we first found that TPNS inhibited the intimal
hyperplasia and reversed the reduced
m6A quantity in balloon
catheter-injured rat carotid artery. Then, we measured the expression profiles of
m6A "writers" (i.e.,
methyltransferase like 3 (METTL3),
methyltransferase like 14 (METTL14), and WT1 associated
protein (WTAP)) and "erasers" (i.e.,
FTO alpha-ketoglutarate dependent dioxygenase (FTO) and
alkB homolog 5, RNA demethylase (ALKBH5)) in vivo and found that TPNS up-regulated the reduced the WTAP expression in balloon
catheter-injured rat carotid artery. Furthermore, we illustrated that TPNS inhibited the viability, proliferation, and migration potential of VSMCs via promotion of WTAP expression and suppression of WTAP restored the TPNS-induced inhibition of cell viability, proliferation and migration potential of VSMCs. In addition, we found that p16 was up-regulated in VSMCs treated with TPNS and repression of p16 restored the TPNS-induced inhibition of cell viability, proliferation and migration potential of VSMCs. Finally, we elucidated that, mechanistically, WTAP exerted its role by regulating p16 via
m6A modification. Collectively, our results reveal the WTAP-p16 signaling axis and highlight the critical roles of
m6A modification in intimal
hyperplasia. Thus, this study provided a potential
biomarker for the assessment of intimal
hyperplasia risk following angioplasty as well as a novel therapeutic target for this disease.