Wan Fang, He Xin, Xie Weidong
State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Shenzhen Key Laboratory of Health Science and Technology, Institute of Biopharmaceutical and Health, Tsinghua University, Shenzhen 518055, China.
Antioxidants (Basel). 2024 Jul 11;13(7):831. doi: 10.3390/antiox13070831.
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.
血管老化是当今心血管疾病高发的原因之一,因为血管细胞会由于各种内部和外部因素而老化。其中,高脂肪是一个重要诱因。卡格列净(CAN)是一种钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂,已被证明除了降低血糖外还具有心血管保护作用,但其具体机制尚不清楚。本研究首先使用棕榈酸(PA)建立血管老化模型,然后测试CAN对PA诱导的血管老化的影响,最后通过活性氧/细胞外信号调节激酶(ROS/ERK)和铁死亡途径研究CAN抗血管老化的机制。我们发现,CAN通过抑制ROS/ERK和铁死亡信号通路的激活来减轻PA诱导的血管细胞老化。本研究从ROS/ERK和铁死亡途径的角度揭示了脂质诱导血管老化和CAN抑制血管老化的新机制,有望为未来相关药物的开发提供新思路。