Dicarbonyl-modified low-density lipoproteins are key inducers of LOX-1 and NOX1 gene expression in cultured human umbilical vein endotheliocytes

Abstract

The expression of LOX-1 and NOX1 genes in human umbilical vein endotheliocytes (HUVECs) when cultured in the presence of low-density lipoproteins (LDL) modified with various natural dicarbonyls was investigated for the first time. It was found that of the investigated dicarbonyl-modified LDLs (malondialdehyde (MDA)-modified LDLs, glyoxal-modified LDLs, and methylglyoxal-modified LDLs), namely MDA-modified LDLs caused the greatest induction of LOX-1 and NOX1 genes, as well as genes of antioxidant enzymes and genes of signaling molecules in HUVECs. MDA-modified LDLs also induce the highest peroxiredoxins expression of the studied antioxidant enzyme genes. The key role of dicarbonyl-modified LDLs in the molecular mechanisms of vascular wall damage and endothelial dysfunction is discussed.