Abstract
Vascular aging is one of the reasons for the high incidence of cardiovascular diseases nowadays, as vascular cells age due to various internal and external factors. Among them, high fat is an important inducer. Canagliflozin (CAN) is one of the SGLT2 inhibitors that has been shown to have cardiovascular protective effects in addition to lowering blood sugar, but the specific mechanism is not clear. This study first established a vascular aging model using palmitic acid (PA), then tested the effect of CAN on PA-induced vascular aging, and finally examined the mechanism of CAN's anti-vascular aging via ROS/ERK and ferroptosis pathways. We found that CAN alleviates PA-induced vascular cell aging by inhibiting the activation of ROS/ERK and ferroptosis signaling pathways. This study reveals new mechanisms of lipid-induced vascular aging and CAN inhibition of vascular aging from the perspectives of ROS/ERK and ferroptosis pathways, which is expected to provide new ideas for the development of related drugs in the future.