m6A demethylase FTO/ALKBH5 promotes diabetes-induced endothelial cell dysfunction by negatively regulating lncRNA H19

m6A levels were decreased in diabetic patients and a diabetic mouse model, while demethylases FTO and ALKBH5 were upregulated.

• High glucose exposure led to reduced m6A levels and increased expression of the demethylases FTO and ALKBH5 in human endothelial cells.
• Silencing FTO and ALKBH5 restored m6A levels and alleviated dysfunction in human umbilical vein endothelial cells (HUVECs) subjected to high glucose.
• Differentially expressed long non-coding RNAs (lncRNAs), including H19, were identified in HUVECs under high glucose conditions.
• FTO and ALKBH5 inhibited H19 expression by decreasing m6A modification in H19 transcripts.
• The FTO/ALKBH5/H19 pathway was implicated in high glucose-induced dysfunction of HUVECs.
• Silencing H19 promoted the expression of cell cycle-related genes by interacting with EZH2 and affecting histone modification.

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