The miR-511-3p/ATP2A2 Axis Is Required for Propofol-Mediated Cardioprotection Against Hypoxia/Reoxygenation Injury.

BACKGROUND

Propofol (PPF) alleviates myocardial ischemia/reperfusion injury (MIRI), yet no existing studies have clarified the function of microRNA-511-3p (miR-511-3p) in cardiac injury or its link to PPF's cardioprotection.

PURPOSE: This study clarified how the miR-511-3p/ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2) signaling cascade mediated PPF-induced relief against hypoxia/reoxygenation (H/R) cardiac damage.

METHODS

H/R damage models were established in H9c2 cells. Cell viability was measured via the CCK-8 assay, and flow cytometry was used to quantify the proportion of apoptotic cells. Cellular reactive oxygen species (ROS) levels were assessed using the DCFH-DA fluorescent staining method. ELISA and colorimetric tests were combined to measure cardiac injury markers, inflammatory mediators, and oxidative stress-related molecules. RT-qPCR was applied to test the expression levels of miR-511-3p and ATP2A2. Dual-luciferase reporter assays were carried out to confirm the direct binding interaction between the two molecules.

RESULTS

PPF markedly boosted the viability and restrained apoptosis of H9c2 cells subjected to H/R treatment. It also reduced the release of cardiac injury markers and eased excessive oxidative stress and inflammatory responses. H/R exposure raised miR-511-3p abundance, an alteration that PPF treatment could reverse. Forced miR-511-3p expression partially abolished the cardioprotective benefits brought by PPF. ATP2A2 was verified as a direct target of miR-511-3p, whose expression was suppressed by this miRNA. Upregulating ATP2A2 counteracted cell damage triggered by miR-511-3p overexpression.

CONCLUSIONS

PPF might mitigate H/R-triggered cardiomyocyte damage, possibly through inhibiting miR-511-3p and increasing its target ATP2A2, and this molecular axis may offer a tentative therapeutic reference for MIRI.