Downregulation of miR-27a-3p induces endothelial injury and senescence and its significance in the development of coronary heart disease.

miR-27a-3p is a multifunctional miRNA that plays a critical role in the process of angiogenesis. However, its specific effect on coronary heart disease (CHD), particularly on the regulation of downstream molecules and the resulting impact on endothelial cell injury, has not yet been fully elucidated. This study aimed to explore the relationship between miR-27a-3p and CHD and its underlying mechanical molecular pathways in CHD patients and modeled endothelial cells with techniques such as RT-qPCR, RNA sequencing and bioinformatics. Consequently, the expression of miR-27a-3p was significantly decreased in CHD patients. In endothelial cells, overexpression of miR-27a-3p was observed to decrease malonaldehyde, gamma H2A histone family member X and interleukin 6 while increased superoxide dismutase, thus reduced endothelial injury and senescence. RNA sequencing and bioinformatics revealed glutamate ionotropic receptor NMDA type subunit 2D (GRIN2D) as a target gene of miR-27a-3p, and dual luciferase assays confirmed the direct binding of miR-27a-3p to the 3'UTR of GRIN2D. Subsequent validation experiments demonstrated that miR-27a-3p inhibited the protein expression of GRIN2D and PKC and suppressed the activation of the MAPK/ERK signaling pathway by reduced downstream MEK and ERK phosphorylation, leading to enhanced endothelial apoptosis. In conclusion, miR-27a-3p played a crucial role in regulating endothelial cell dysfunction which may trigger coronary atherosclerosis and CHD by targeting GRIN2D in the PKC/MEK/ERK signaling pathway.