Plasma fibronectin alleviate acrolein-induced ferroptosis via AMPK/Nrf2 pathway in HUVEC.

Ferroptosis is a programmed cell death implicated in several diseases like lung inflammation, diabetes, and cardiovascular diseases. Acrolein, a common environmental pollutant, has been demonstrated to induce ferroptosis in various kinds of cells. Plasma fibronectin (FN), a glycoprotein found in the extracellular matrix, has anti-inflammatory and antioxidant properties. While FN has been reported to have both protective and detrimental effects in atherosclerosis, its role in ferroptosis remains unexplored. In this study, we investigated the effects of acrolein on ferroptosis in HUVEC as an in vitro model of atherosclerosis and explored the potential protective role of FN. Here, acrolein induced ferroptosis in endothelial cells, leading to cell death, elevated levels of MDA, increased levels of intracellular ferrous iron, ACSL4 and TFRC, and decreased levels of GPX4 and SLC7A11, which are ferroptosis-related biomarkers. Our findings indicate that FN protected against acrolein-induced ferroptosis in endothelial cells by reducing lipid peroxidation and inflammation, as well as reversing the changes in ferroptosis biomarkers. This protective effect is mediated through the activation of the AMPK/Nrf2 signaling pathway, which upregulates the expression of GPX4 and SLC7A11, key regulators of ferroptosis. Therefore, this study provides new insights into the potential protective role of FN in HUVEC injury by mitigating acrolein-induced ferroptosis.