Upregulation of miR-223-3p in diabetic cardiomyopathy modulates disease progression via the GRK2/NLRP3 signaling pathway.

BACKGROUND AND

OBJECTIVE

As a significant diabetic complication, diabetic cardiomyopathy (DCM) manifests with the pathological features of myocardial fibrosis and inflammation. This investigation was to elucidate the function of miR-223-3p and its interaction with G protein-coupled receptor kinase 2 (GRK2) and NLRP3 inflammasome in DCM progression.

METHODS

Diabetic (db/db) mice were treated with a miR-223-3p inhibitor or saline. In vitro, H9C2 cardiomyocytes were exposed to high glucose and transfected with miR-223-3p inhibitor/mimic or GRK2/NLRP3 modulators. Fibrosis, inflammation, and apoptosis were evaluated using qRT-PCR, Western blot, apoptosis assays, and histopathology.

RESULTS

High glucose elevated miR-223-3p expression, correlating with increased GRK2, NLRP3, fibrosis, and apoptosis markers. Inhibition of miR-223-3p attenuated these pathological trends in cells and diabetic mice, while GRK2/NLRP3 overexpression reversed the protective effects. Conversely, suppressing GRK2/NLRP3 mitigated miR-223-3p mimic-induced fibrosis and apoptosis.

CONCLUSIONS

miR-223-3p exacerbates DCM by activating GRK2/NLRP3 signaling, highlighting its therapeutic potential. Targeting this axis could offer novel strategies to combat diabetic cardiac complications.