ArticleCardiovascular drugs and therapy2026
miR‑18a‑5p Serves as a Diagnostic and Prognostic Biomarker and Attenuates Hypoxia‑Induced Cardiac Microvascular Endothelial Injury by Targeting the HIF1A/NF‑κB Pathway in Chronic Heart Failure.
Article in Cardiovascular drugs and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeChronic 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.
methodsA 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.
resultsIn 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.
conclusionmiR-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.
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