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Cardiovascular disease of atherosclerotic origin is the main cause of death in diabetes mellitus and metabolic syndrome. One of the mechanisms involved in such increased risk is the high incidence of lipoprotein modification in these pathologies. Increased glycosylation, oxidative stress or high non-esterified fatty acid levels in blood, among other factors, promote the modification and subsequent alteration of the properties of lipoproteins. Since the modification of low-density lipoprotein (LDL) is the triggering factor in the development of atherosclerosis, considerable research has been focused on the quantification of modified LDLs in blood to be used as biomarkers of cardiovascular risk. The present review deals with the main molecular mechanisms involved in the modification of LDL in diabetes and metabolic syndrome and briefly describe the atherogenic effects that these modified LDLs exert on the arterial wall. The possibility of using the high levels of modified LDLs or their immunocomplexes as a predictive tool for cardiovascular risk in diabetes-related pathologies is also discussed.

Electronegative LDL (LDL(-)) is a minor modified LDL subfraction that promotes cytokine release by human mononuclear cells. The aim of the current study was to evaluate changes in gene expression induced by LDL(-) versus native LDL in lymphocytes and monocytes. Therefore, mononuclear cells were incubated with these LDL subfractions and their effects on expression in human whole genome were analyzed by gene array. Differential expression of the genes was quantified by real-time RT-PCR. LDL(-) altered the gene expression pattern, particularly of inflammatory genes. LDL(-) down-regulated CD36 and colony-stimulating factor 1 receptor (CSF1R) genes and up-regulated Fas expression and Fas protein on cellular membrane. LDL(-) seemed to promote the alterations in these genes by activation of NF-kB and inhibition of AP1 and PPARG. In conclusion, LDL(-) induced changes in gene expression in monocytes and lymphocytes. Fas up-regulation suggests a proinflammatory action; however, CSF1R and CD36 down-regulation could decrease monocyte differentiation and activation. Therefore, LDL(-) promoted not only inflammatory effects but also counteracting actions in circulating mononuclear cells.