Sexually Dimorphic Regulation of MiR-29a/c-3p in Human Endothelial Cells: Cell Functions and Transcriptome

MiR-29a/c-3p were downregulated using miR-29c-3p inhibitors in HUVECs, followed by assessing chemotactic and proliferative responses to VEGFA and FGF2. RNA-seq analysis was conducted to profile transcriptomic changes. Compared with negative control, miR-29c-3p inhibitors suppressed over 90% of miR-29a/c-3p in HUVECs at 48 h.

MiR-29c-3p inhibitors decreased VEGFA-stimulated chemotaxis by 25% in male, but not female HUVECs. MiR-29c-3p inhibitors did not alter FGF2-stimulated chemotaxis or VEGFA- and FGF2-stimulated proliferation in HUVECs. RNA-seq revealed that miR-29a/c-3p inhibitors differentially altered the transcriptome between female and male HUVECs.

Functional enrichment analyses showed that miR-29a/c-3p-regulated genes were differently associated with hypertension, heart, angiogenesis, and immunology in female and male HUVECs. These data demonstrate that knockdown of miR-29a/c-3p differentially affects cellular responses to angiogenic factors in female and male HUVECs, in association with disrupted transcriptome. These miR-29a/c-3p-regulated genes might serve as sex-specific therapeutic targets for PE-associated vascular dysfunction.