Mitigation of arteriosclerosis through transcriptional regulation of ferroptosis and lipid metabolism by magnesium

Abstract

Metallic cardiovascular stents are crucial for preventing atherosclerosis-induced infarction by offering mechanical support. However, the effects of metal ions released from these stents on atherosclerosis remain ambiguous. This study evaluates the potential impact posed by the degradation products of magnesium-based stents, with a focus on ferroptosis, a key mechanism driving atherosclerosis. Remarkably, our results demonstrate that Mg effectively inhibits ferroptosis in human umbilical vein endothelial cells and in murine, rat and rabbit models. Our studies reveal that magnesium ions impede the dephosphorylation of ERK proteins, thereby enhancing the expression of SLC7A11 and GCL proteins via activation of the MAPK pathway mechanistically. Additionally, magnesium ions downregulate ACSL4 protein expression, leading to decreased levels of acyl-CoA and ether-phospholipids. Eventually, multiple animal experiments indicate that biodegradable Mg stents can inhibit ferroptosis and decelerate the progression of arteriosclerosis, highlighting the therapeutic potential of Mg stents in treating arteriosclerosis.