Canagliflozin Delays Aging of HUVECs Induced by Palmitic Acid via the ROS/p38/JNK Pathway

Abstract

Vascular aging is an important factor contributing to cardiovascular diseases, such as hypertension and atherosclerosis. Hyperlipidemia or fatty accumulation may play an important role in vascular aging and cardiovascular diseases. Canagliflozin (CAN), a sodium-glucose cotransporter inhibitor, can exert a cardiovascular protection effect that is likely independent of its hypoglycemic activities; however, the exact mechanisms remain undetermined. We hypothesized that CAN might have protective effects on blood vessels by regulating vascular aging induced by hyperlipidemia or fatty accumulation in blood vessel walls. In this study, which was undertaken on the basis of aging and inflammation, we investigated the protective effects and mechanisms of CAN in human umbilical vein endothelial cells induced by palmitic acid. We found that CAN could delay vascular aging, reduce the secretion of the senescence-associated secretory phenotype (SASP) and protect DNA from damage, as well as exerting an effect on the cell cycle of senescent cells. These actions likely occur through the attenuation of the excess reactive oxygen species (ROS) produced in vascular endothelial cells and/or down-regulation of the p38/JNK signaling pathway. In summary, our study revealed a new role for CAN as one of the sodium-dependent glucose transporter 2 inhibitors in delaying lipotoxicity-induced vascular aging by targeting the ROS/p38/JNK pathway, giving new medicinal value to CAN and providing novel therapeutic ideas for delaying vascular aging in patients with dyslipidemia.

Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature

“…Moreover, in mouse embryos overexpressing the HMGA1 P6 pseudogene, the mice grew faster and aged later [ 45 ]. These are associated with the activation of the p38MAPK pathway [ 43 , 46 ]. The secretion of SASP can be regulated using components of the drug action regulation pathway to treat diseases, such as tumors, diabetes, and tendinopathy [ 11 , 47 ].…”

Antibacterial Activity and Mechanism of Canagliflozin against Methicillin-Resistant Staphylococcus aureus

“…Canagliflozin promotes urinary glucose excretion, increases energy expenditure, aids in weight loss, and reduces cardiovascular risk [17,18]. Moreover, canagliflozin has anti-inflammatory [18][19][20][21][22], anti-aging [23] and anti-tumor effects [24]. It is also proposed for use in the treatment of autoimmune diseases [25] and improves the gut microbiota [26,27].…”