Herein, we explored the effect of NAT10-induced ac4C acetylation on endothelial dysfunction and EndMT in hypertension and clarified the mechanism through which the NAT10/ac4C/AdipoR1/PGC-1α axis inhibits endothelial dysfunction via the regulation of mitochondrial biogenesis and function. Here, PPARGC1A is linked to hypertensive disorder.