3.3.1 Ferroptosis is involved in the pathophysiology of hypertension
Existing studies have found that ferroptosis is involved in endothelial cell dysfunction, which can lead to changes in vasomotor function and cause hypertension11. Vascular smooth muscle cells (VSMCs), as one of the main cellular components of the vascular wall, can maintain the tension of the vascular wall through a slow and mild contraction. The phenotypic transformation of VSMCs is closely related to the pathophysiological process of hypertension. Recent studies have found that ferroptosis can induce the transition of VSMCs from contractile phenotype to synthetic phenotype90. This suggests that ferroptosis is related to the pathogenesis of hypertension.
Many studies have shown that ROS plays an important role in vascular remodeling and endothelial dysfunction associated with hypertension. Increased ROS can promote endothelial dysfunction, and accelerate VSMCs proliferation and vascular remodeling, leading to vascular injury, increased peripheral resistance, and elevated blood pressure91,92. An important feature of ferroptosis is an increase in intracellular ROS levels. A recent in vitro study found that VSMC undergoes ferroptosis under high hydrostatic pressure, accompanied by iron accumulation, increased ROS production, and lipid peroxidation7.In addition, it has been proposed that lenvatinib can induce ferroptosis in endothelial cells, which subsequently leads to vascular dysfunction and hypertension13. The above studies have proved that ferroptosis is involved in the pathophysiology of hypertension.