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.

We investigated the role of mammalian target of rapamycin/nuclear factor-kappa B (mTOR/NF-κB) signaling pathway in high thoracic epidural anesthesia (HTEA) against myocardial ischemia-reperfusion (I/R) injury in rats. The rat model of myocardial I/R injury was established. Ninety rats were divided into the normal, sham, I/R, eHTEA, the PDTC, and HTEA + PDTC groups. ELISA was applied to detect cardiac function indexes. HE staining was conducted to observe histopathological changes of myocardial tissues, and TTC staining was performed to detect the myocardial infarction size. TUNEL staining was adopted to detect the cell apoptosis rate. The mRNA and protein levels of mTOR, NF-κB, Fasl, Bcl-2 and Bax, and LC3-I, LC3-II, BNIP3, and Atg5 were detected by RT-qPCR and Western blotting, respectively. The findings indicated that compared with the normal and sham groups, the I/R, PDTC, and HTEA groups showed the larger myocardial infarction size and increased cell apoptosis rate, while the results in the HTEA + PDTC group were opposite. Compared with the normal and sham groups, the I/R group showed reduced mRNA and protein levels of Bcl-2, LC3, BNIP3, and Atg5, and elevated mRNA and protein levels of mTOR, p50, p65, Bax, and Fasl, while the HTEA + PDTC group revealed the opposite results, and the PDTC and HTEA group revealed the increased mRNA and protein levels of Bcl-2, LC3, BNIP3, Atg5, mTOR, p50, p65, Bax, and Fasl. These results prove that the inhibition of mTOR/NF-κB signaling pathway potentiates HTEA against myocardial IR injury by autophagy and apoptosis in rats.