The molecular mechanism of MiR-26a-5p regulates autophagy and activates NLRP3 inflammasome to mediate cardiomyocyte hypertrophy

Objective: Many studies have found that miR-26a-5p plays an essential role in the progression of pathological cardiac hypertrophy, however, there is still no evidence on whether miR-26a-5p is related to the activation of Autophagy and NLRP3 inflammasome. And the mechanism of miR-26a-5p and NLRP3 inflammasome aggravating pathological cardiac hypertrophy remain unclear.

Methods: Cardiomyocytes were treated with 200µM PE to induce cardiac hypertrophy and intervened with 10mM NLRP3 Inhibitor INF39. In addition, we also used the MiR-26a-5p mimic and inhibitor to transfect PE-induced cardiac hypertrophy. RT-qPCR and western blotting were used to detect the expressions of miR-26a-5p, NLRP3, ASC and Caspase-1 in each group, and we used α-SMA immunofluorescence to detect the change of cardiomyocyte area. The expression levels of Autophagy proteins LC3, beclin-1 and p62 were detected by western blotting. Finally, we induced the SD rat cardiac hypertrophy model through aortic constriction (TAC) surgery. In the experimental group, rats were intervened with MiR-26a-5p mimic, MiR-26a-5p inhibitor, Autophagy Inhibitor 3-MA, and Autophagy activator Rapamycin.

Results: In cell experiments, we observed that the expression of miR-26a-5p was associated with cardiomyocyte hypertrophy and increased surface area. Furthermore, miR-26a-5p facilitated Autophagy and activated the NLRP3 inflammasome pathway, which caused changes in the expression of genes and proteins including LC3, beclin-1, p62, ACS, NLRP3, and Caspase-1. We discovered similar outcomes in the TAC rat model, where miR-26a-5p expression corresponded with cardiomyocyte enlargement and fibrosis in the cardiac interstitial and perivascular regions. In conclusion, miR-26a-5p has the potential to regulate Autophagy and activate the NLRP3 inflammasome, contributing to the development of cardiomyocyte hypertrophy.

Conclusion: Our study found a relationship between the expression of miR-26a-5p and cardiomyocyte hypertrophy. The mechanism behind this relationship appears to involve the activation of the NLRP3 inflammasome pathway, which is caused by miR-26a-5p promoting Autophagy. Targeting the expression of miR-26a-5p, as well as inhibiting the activation of Autophagy and the NLRP3 inflammasome pathway, could offer additional treatments for pathological cardiac hypertrophy.

Apoptosis; Autophagy; Cardiac hypertrophy; Cardiomyocytes; miR-26a-5p.