The primary novel findings in the present study are that FNDC5 deficiency aggravates Ang II-induced hypertension, vascular oxidative stress, NLRP3 inflammasome activation, and vascular remodeling in mice, and that exogenous FNDC5 alleviates the Ang II-induced oxidative stress and NLRP3 inflammasome activation in VSMCs. The gene discussed is AGT; the disease is hypertensive disorder.