Rare earth element lanthanum protects against atherosclerosis induced by high-fat diet via down-regulating MAPK and NF-κB pathways

Rare earth elements, which are extensively used in environmental protection, medicine, food, aerospace and other fields, have attracted widespread attention in recent years. However, the effect on atherosclerosis and its biological mechanism remains unclear. To elucidate these problems, here we performed a study that Apolipoprotein E-deficient mice were fed with high-fat diet to promote the development of atherosclerosis, meanwhile, mice were received 0.1, 0.2, 1.0, 2.0 mg/kg lanthanum nitrate (La(NO₃)₃) for 12 weeks. The results showed that La(NO₃)₃ prominently inhibited aorta morphological alternations by histopathological examination. Meanwhile, La(NO₃)₃ regulated serum lipids, including reducing total cholesterol and increasing high-density lipoprotein. Moreover, the oxidative stress was alleviated by La(NO₃)₃ intervention through enhancing superoxide dismutase and glutathione, and decreasing malondialdehyde levels. In addition, enzyme-linked immunosorbent assay analysis showed La(NO₃)₃ could ameliorate the dysfunction of vascular endothelium with declined endothelin-1 and increased prostacyclin. Furthermore, Western blot analysis indicated that La(NO₃)₃ significantly down-regulated inflammation-mediated proteins including phosphorylated p38 mitogen-activated protein kinases (p-p38 MAPK), monocyte chemo-attractant protein, intercellular adhesion molecule-1, nuclear factor-kappa B p65 (NF-κB p65), tumor necrosis factor-α, interleukin-6 and interleukin-1β, whereas up-regulated the inhibitor of NF-κB protein. In conclusion, La(NO₃)₃ ameliorates atherosclerosis by regulating lipid metabolism, oxidative stress, endothelial dysfunction and inflammatory response in mice. The potential mechanism associates with the inhibition of MAPK and NF-κB signaling pathways.

Keywords: Atherosclerosis; La(NO(3))(3); MAPK signaling Pathway; NF-κB signaling pathway; Rare earth elements.