miR-130a-3p Exacerbates Sepsis-Induced Cardiac Dysfunction by Promoting Inflammation and Targeting PDK4

Abstract

Background Sepsis is frequently complicated by systemic inflammatory injury and cardiac dysfunction, which serve as risk factors of adverse clinical outcomes and increased mortality risk. To clarify the function of miR-130a-3p in sepsis diagnosis and its regulatory role in sepsis-induced inflammatory injury and cardiac dysfunction, based on clinical analysis and cellular assays. Methods The study recruited 126 patients with sepsis and an matched number of healthy controls. The potential of miR-130a-3p to differentiate between sepsis and healthy controls was evaluated by receiver operating characteristic (ROC) curve. Quantify miR-130a-3p and PDK4 levels using real-time quantitative polymerase chain reaction (RT-qPCR). Indicators of inflammation, cardiac dysfunction and oxidative stress in cells were assessed by corresponding biochemical assays and enzyme-linked immunosorbent assay (ELISA) kits. The functional properties of H9C2 cells were evaluated by cell counting kit-8 (CCK-8) assay and flow cytometry. Bioinformatics analysis and luciferase activity assays were employed to identify the downstream targets of miR-130a-3p. Results H9C2 cell viability was impaired, with the increased levels of interleukin-1beta (IL-1β), interleukin-6 (IL-6), cardiac troponin I (cTnI), creatine kinase MB (CK-MB), malondialdehyde (MDA), and decreased superoxide dismutase (SOD) activity. When miR-130a-3p expression was repressed, the levels of inflammation and cardiac dysfunction indicators were diminished, and the oxidative stress damage and cell viability was restored. PDK4 is a direct target of miR-130a-3p and is low-expressed in sepsis patients and LPS-induced H9C2 cells. Conclusion miR-130a-3p modulates inflammatory response and cardiac dysfunction by mediating PDK4, representing a potential effective target for sepsis diagnosis and intervention.