Association between Nfr2, HO-1, NF-kB Expression, Plasma ADMA, and Oxidative Stress in Metabolic Syndrome.

Endothelial dysfunction is one of the major factors in the pathogenesis of metabolic syndrome (MetS), and its molecular mechanisms are not completely understood. The present study aimed to examine the connection between nuclear factor2-related factor2 (Nrf2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), heme oxygenase 1 (HO-1), and plasma asymmetric dimethylarginine (ADMA) and malondialdehyde (MDA) in people with MetS. Participants in the study were as follows: with MetS (n = 30) and without MetS (Control) (n = 14). Expression of Nrf2, NF-kB, and HO-1 was measured in peripheral blood mononuclear cells (PBMCs). Plasma ADMA was determined using the ELISA technique and MDA via the thiobarbituric acid method. Our study showed that mRNA of NF-kB, Nrf2, and HO-1 levels in PBMCs in the MetS group were significantly higher than in the controls by 53%, 130%, and 185% (p < 0.05), respectively. Similarly, elevated levels of MDA (by 78%, p < 0.001) and ADMA (by 18.7%, p < 0.001) were established in the MetS group. Our findings show the importance of transcription factor Nrf2, playing an integral role in the protection of the endothelium, and of NF-κB, a transcription factor mediating the inflammatory response in MetS. Knowledge of complex cellular-molecular mechanisms would allow the use of biomarkers such as Nrf2, NF-kB, HO-1, and ADMA for the assessment of endothelial dysfunction in clinical practice.

Molecular mechanisms associating oxidative stress with endothelial dysfunction in the development of various vascular complications in diabetes mellitus.

Endothelial dysfunction plays a key role in the pathogenesis of microangiopathy and macroangiopathy in type 2 diabetes mellitus. The endothelial dysfunction is induced by some cell metabolism disorders which are implicated in the pathogenesis of micro- and macroangiopathies through the principal mediation of oxidative stress. The discussion focuses preferentially on the recently found molecular mechanisms of free radical generation and on the endothelial disorders resulting from some free-radical-induced abnormalities in the intracellular signal pathways. We specify the molecular targets in the vascular complication therapy of diabetes on the basis of evidence of association between oxidative stress, metabolic abnormalities and endothelial dysfunction.