Trans‐Fatty Acids ( <scp>TFA</scp> ) 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.