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Fig. 5 | Cardiovascular Diabetology

Fig. 5

From: MicroRNAs and obesity-induced endothelial dysfunction: key paradigms in molecular therapy

Fig. 5

Obesity, oxidative stress, miRNAs and endothelial function. Superoxide anions (O·2 ) are mainly produced by NOX2, NOX4 and mitochondria through electron transport chain complex I and III. Under physiological conditions, O·2 are highly regulated by antioxidant mechanism through SOD that detoxifies O·2 to hydrogen peroxide (H2O2), which is then converted to water (H2O) by catalase or glutathione peroxidase (GSHPx) and peroxiredoxins (PRDXs). Obesity interferes with the normal workings of this system. By decreasing miR-448-3p and miR-19b, it increases NOX2 levels. At the same time, it decreases miR-25 while increasing miR-146a, which can cause up or downregulation of NOX4 levels respectively (NOX4 has dual effect). Additionally, obesity increases the levels of miR-210 and miR-29, both of which affect the mitochondrial respiratory chain. Moreover, obesity modulates the levels of miRNAs that regulate the antioxidant system (e.g. miR-21 and miR-17, both of which target SOD, with miR-17 additionally targeting GSHPx; and miR-23b and miR-200c, both of which target PRDXs). Altogether, the modulation of miRNA levels during obesity leads to excessive production of O·2 and consequently endothelial dysfunction. SOD: Superoxide dismutase; GSHPx: glutathione peroxidase; PRDXs: peroxiredoxins; NOX2: catalytic, membrane-bound subunit of NADPH oxidase; NOX4: NADPH oxidase homolog

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