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Fig. 1 | Clinical Epigenetics

Fig. 1

From: Epigenetic mechanisms of endothelial dysfunction in type 2 diabetes

Fig. 1

Glycemia-associated epigenetic mechanisms involved in NF-kB proinflammatory activity. Panels ab. Cells exposed to high glucose exhibit upregulated expression of the NF-kB subunit of p65 gene, monomethylation of histone 3 at lysine 4 (H3K4), and demethylation of H3K9 in the p65 promoter region. Moreover, hyperglycemia induces NF-kB transcription factor activation through stimulation of upstream pathways, increasing the synthesis of inflammatory mediators (IL-6, VCAM-1, MCP-1) and the expression of anti-inflammatory microRNAs, e.g., miR-146a. Under persistent hyperglycemic conditions miR-146a cannot restrain the effect of upstream proinflammatory stimuli on NF-kB activation. Panel c shows that anti-diabetic agents can reduce proinflammatory stimuli on the NF-Kb pathway, restraining p65 activation and miR-146a expression but does not alter H3K4 monomethylation and H3K9 demethylation in the p65 promoter region. The phenomenon may explain why the cardiovascular complications of diabetes progress even in presence of optimal glycemic control. AGE, advanced glycation end-products; DAMP, damage-associated molecular patterns; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; RAGE, receptor for advanced glycation end-products; VCAM-1, vascular cell adhesion molecule-1; TLR-4, toll-like receptor 4

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