Further investigation revealed that NAT10 inhibits endothelial dysfunction in hypertension through remodeling the ac4C modification of MAPK signaling-related mRNAs, including AdipoR1. Moreover, NAT10-induced AdipoR1 expression facilitates mitochondrial biogenesis and function in Ang II-treated ECs via the p38 MAPK/PGC-1α pathway. Here, NAT10 is linked to endothelial dysfunction.