In summary, relying on the modulation of Ang II cascade, AMPKα activity, and NF-κB transcription activity, VSMC-derived SIRT1 exerts pivotal protective effects on blood pressure control and hypertension-related vascular remodeling and arterial stiffness, which may improve the long-term clinical prognosis in addition to the currently used anti-hypertensive drugs. The gene discussed is SIRT1; the disease is hypertensive disorder.