Trans-Fatty Acids (TFA) Induced Vascular Injury Through the Regulation of the Sirt1-Ppargc1a-Nfe2l2 Signaling Pathway in Male Rats

Dietary trans-fatty acids (TFA) elevate cardiovascular disease (CVD) risk by driving vascular injury, yet the mechanisms underlying this effect remain largely unexplored. Eighteen male Sprague–Dawley (SD) rats were randomly assigned to three groups: control group, a low-dose TFA diet group, and a high-dose TFA diet group. During the 12-week experiment, body weight, food intake, and blood pressures were monitored. Post-experiment, serum triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were quantified using assay kits. Network pharmacology, molecular docking, and western blotting were employed to predict and validate the toxicological mechanisms underlying TFA-induced vascular injury. TFA significantly induced mitochondrial damage in the vascular tissues of rats. TFA consumption increased serum TC, TG, and LDL-C levels while reducing HDL-C levels in rats. Network pharmacology analysis revealed significant enrichment in apoptotic pathways, highlighting the pivotal roles of Sirt1, Ppargc1a, and Nfe2l2 in the mechanistic network underlying TFA-induced vascular injury. Furthermore, molecular docking and western blotting analyses validated substantial changes in protein expression linked to apoptosis and the Sirt1-mediated signaling pathway. TFA induces mitochondrial damage, elevating reactive oxygen species levels and triggering vascular apoptosis in rats. This process is mediated by modulation of the Sirt1/Ppargc1a/Nfe2l2 signaling pathway. These findings clarify a critical mechanism of TFA-induced vascular injury, highlighting dietary TFA as a modifiable risk factor for cardiovascular health.