microRNA-363-3p reduces endothelial cell inflammatory responses in coronary heart disease via inactivation of the NOX4-dependent p38 MAPK axis

Coronary heart disease (CHD) is one of the leading causes of heart-associated deaths worldwide. This study aimed to investigate the mechanism by which microRNA-363-3p (miR-363-3p) regulates endothelial injury induced by inflammatory responses in CHD. The expression patterns of miR-363-3p, NADPH oxidase 4 (NOX4), and p38 MAPK/p-p38 MAPK were examined in an established atherosclerosis (AS) model in C57BL/6 mice and in isolated coronary arterial endothelial cells (CAECs) after gain-or loss-of-function experiments. We also measured the levels of inflammatory factors (IL-6, ICAM-1, IL-10 and IL-1?), hydrogen peroxide (H2O2), and catalase (CAT) activity, followed by detection of cell viability and apoptosis. In AS, miR-363-3p was downregulated and NOX4 was upregulated, while miR-363-3p was identified as targeting NOX4 and negatively regulating its expression. The AS progression was reduced in NOX4 knockout mice. Furthermore, miR-363-3p resulted in a decreased inflammatory response, oxidative stress, and cell apoptosis in CAECs while augmenting their viability via blockade of the p38 MAPK signaling pathway. Overall, miR-363-3p hampers the NOX4dependent p38 MAPK axis to attenuate apoptosis, oxidative stress injury, and the inflammatory reaction in CAECs, thus protecting CAECs against CHD. This finding suggests the miR-363-3p-dependent NOX4 p38 MAPK axis as a promising therapeutic target for CHD.

Automated summary

The study demonstrates that miR-363-3p negatively regulates NOX4 in coronary arterial endothelial cells (CAECs) through blocking the p38 MAPK signaling pathway, leading to reduced inflammation, oxidative stress, and apoptosis while improving cell viability. This protective mechanism of miR-363-3p against coronary heart disease (CHD) suggests it as a potential therapeutic target for CHD.