Protective Effects of Microrna-22 Against Endothelial Cell Injury by Targeting NLRP3 Through Suppression of the Inflammasome Signaling Pathway in a Rat Model of Coronary Heart Disease

Abstract

Background/Aims: This study aimed to identify the role of microRNA-22 (MIR-22) in endothelial cell (EC) injury in coronary heart disease (CHD) by targeting NLRP3 through the inflammasome signaling pathway. Methods: A total of 24 healthy male Sprague-Dawley (SD) rats were divided into normal and atherosclerosis groups. The atherosclerosis rats were assigned into blank, negative control (NC), MIR-22 mimic, MIR-22 inhibitor and MIR-22 inhibitor + siNLRP3 groups. A luciferase reporter gene assay was used to detect the relationship between MIR-22 and NLRP3. MIR-22 expression as well as NLRP3 and caspase-1 mRNA and protein expression were measured using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The activity and apoptosis of coronary arterial endothelial cells (CAECs) were determined by MTT and Hoechst 33258. CAEC lumen formation was detected by a lumen formation assay. An enzyme-linked immunosorbent assay (ELISA) was used to detect IL-1β, IL-6, IL-10 and IL-18 levels. Results: The results indicated that the atherosclerosis group significantly decreased MIR-22 expression but increased NLRP3 and caspase-1 mRNA and protein expression. The cell survival rate was significantly increased in the MIR-22 mimic group and significantly reduced in the MIR-22 inhibitor group. The MIR-22 mimic group displayed a lower apoptosis rate and more cells with obvious lumen walls and numerous tubular structures, while cells in the MIR-22 inhibitor group were unable to form lumen walls and had a scattered distribution compared to the blank group. The ELISA showed that IL-1β, IL-6 and IL-18 levels were markedly decreased, while IL-10 was clearly increased in the MIR-22 mimic group. In contrast, in the MIR-22 inhibitor group, IL-1β, IL-6 and IL-18 levels were significantly increased, and IL-10 levels were decreased. Conclusion: Our findings indicated that MIR-22 could lower the levels of pro-inflammatory cytokines by inhibiting the NLRP3 inflammasome pathway, which suppresses CAEC apoptosis and protects CAECs in rats with CHD.