Chronic heart failure (CHF) is a severe end-stage cardiovascular syndrome with high mortality and poor prognosis. This study aimed to investigate the expression, diagnostic, and prognostic value of serum miR-18a-5p in CHF patients and to explore its molecular mechanism in regulating hypoxia-induced injury. A total of 125 CHF patients and 125 healthy controls were enrolled. The expression of miR-18a-5p was detected by RT-qPCR. The diagnostic efficacy was evaluated by the ROC curve. The prognostic value was analyzed by Kaplan-Meier survival analysis and multivariate Cox regression. Human cardiac microvascular endothelial cells (hCMECs) were used to establish a hypoxic injury model. Cell viability, apoptosis, and inflammatory cytokines were measured by CCK-8, flow cytometry, and ELISA. The targeting relationship between miR-18a-5p and HIF1A was verified by a dual-luciferase reporter assay. The expression of apoptosis, fibrosis, and NF-κB pathway proteins was detected by RT-qPCR and Western blot. In patients with CHF, circulating miR‑18a‑5p was markedly downregulated, exhibiting a diagnostic AUC value of 0.874. Diminished miR‑18a‑5p expression was closely linked to decreased LVEF, increased levels of BNP and cTnI, higher NYHA classification, and a poorer long‑term prognosis. miR-18a-5p was a protective factor for CHF. In vitro, overexpression of miR-18a-5p enhanced cell viability, inhibited apoptosis, reduced the secretion of pro-inflammatory factors, and downregulated collagen I, collagen III, and α-SMA expression in hypoxic hCMECs. miR-18a-5p targeted HIF1A 3’UTR and negatively regulated HIF1A/NF-κB signaling. Overexpression of HIF1A reversed the protective effects of miR-18a-5p. miR-18a-5p attenuates hypoxia-induced inflammation, apoptosis, and fibrosis by targeting the HIF1A/NF-κB pathway. Circulating miR-18a-5p therefore holds promising clinical prospects as a non-invasive serum biomarker for CHF diagnosis and risk stratification. Upregulation of miR-18a-5p provides a potential molecular strategy for preventing hypoxia-mediated cardiac microvascular remodeling in chronic heart failure.
Myocardial infarction (MI) leads to heart cell death and inflammation, resulting in permanent heart damage. Exosomes derived from mesenchymal stem cells (MSCs), which can deliver miRNAs to cells, have shown potential as therapeutic agents for MI, this study sought to elucidate the role of MSC-derived exosomal miRNA-335-5p in MI. Exosomes secreted from MSCs were observed using transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA). Inflammatory cytokines, cell apoptosis were evaluated. The dual luciferase gene assay was used to validate the interaction between miRNA-335-5p and BCL2-like 11 (BCL2L11). Cardiac function indicators in MI rats were detected using echocardiography. The levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB) and cardiac troponin (cTnI) were detected by commercial kits. To confirm fibrosis detection, Masson staining was employed. MSCs-derived exosomes (MSC-exos) are abundant in miR-335-5p. MSCs-derived exosomal miR-335-5p inhibited hypoxia induced H9c2 cells apoptosis and inflammation, while reducing miRNA-335-5p in MSC-exos does not produce this effect. Mechanically, miRNA-335-5p interacted with BCL2L11 and reduced its expression. Reducing miRNA-335-5p in MSC-exos or overexpressing BCL2L11 can counteract the improvement of MSC-exos on apoptosis and inflammation in H9c2 cells under hypoxic conditions and MI rats. In MI, MSCs-derived exosomal miRNA-335-5p alleviated apoptosis and inflammation by targeting BCL2L11. MSCs-derived exosomes are abundant in miR-335-5p. MSCs-derived exosomal miR-335-5p inhibited hypoxia induced H9c2 cells apoptosis and inflammation. By targeting BCL2L11, miRNA-335-5p can decrease its level. MSCs-derived exosomal miRNA-335-5p inhibited BCL2L11 and improved apoptosis and inflammation in MI in vitro and in vivo models.
