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Canagliflozin Inhibits Palmitic Acid-Induced Vascular Cell Aging In Vitro through ROS/ERK and Ferroptosis Pathways
Fang Wan1,2, Xin He1,2,3, Weidong Xie1,2,3
1State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
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.
Insights
Canagliflozin (CAN) protects against high-fat-induced vascular aging by inhibiting ROS/ERK and ferroptosis pathways. This reveals new mechanisms for preventing cardiovascular disease and developing future lipid-lowering therapies.
Area of Science:
- Cardiovascular Science
- Cellular Aging
- Pharmacology
Background:
- Vascular aging contributes significantly to cardiovascular disease incidence.
- High-fat diets are key inducers of vascular cell aging.
- Canagliflozin (CAN), an SGLT2 inhibitor, shows cardiovascular benefits, but its mechanism remains unclear.
Purpose of the Study:
- To investigate the effects of CAN on palmitic acid (PA)-induced vascular aging.
- To elucidate the underlying mechanisms of CAN's anti-aging effects in vascular cells.
- To explore the roles of ROS/ERK and ferroptosis pathways in lipid-induced vascular aging.
Main Methods:
- Establishment of a vascular aging model using palmitic acid (PA).
- Treatment of the aging model with Canagliflozin (CAN).
- Analysis of ROS/ERK and ferroptosis signaling pathways.
Main Results:
- CAN effectively alleviates PA-induced vascular cell aging.
- CAN inhibits the activation of ROS/ERK signaling pathways.
- CAN suppresses ferroptosis signaling pathways in aged vascular cells.
Conclusions:
- CAN demonstrates protective effects against lipid-induced vascular aging.
- Inhibition of ROS/ERK and ferroptosis pathways is a key mechanism for CAN's action.
- Findings offer novel insights into vascular aging and potential therapeutic strategies.
