Regulation of angiogenesis in cerebral ischemic rats through ceRNA networks and its impact on cerebral ischemic stroke prognosis.

Abstract

BACKGROUND: Cerebral ischemic stroke (CIS) represents a major cerebrovascular disorder characterized by high incidence and disability rates, significantly compromising patient quality of life and survival. Angiogenesis demonstrates potential for improving post-ischemic cerebral blood flow and reducing infarct volume, though its regulatory mechanisms require further elucidation. METHODS: We established a permanent focal middle cerebral artery occlusion (pMCAO) rat model and performed whole transcriptome sequencing. Differential expression analysis identified dysregulated long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs). Regulatory networks (circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA) were constructed using differential expression data and public databases. mRNAs within networks underwent functional enrichment and protein-protein interaction (PPI) analysis to investigate angiogenic mechanisms. RESULTS: Ischemia-hypoxia altered circRNA, lncRNA, and miRNA expression profiles, modulating angiogenesis through specific pathways. The circRNA/lncRNA-miRNA-mRNA networks implicated angiogenesis-related pathways including Cytokine-cytokine receptor interaction and cAMP signaling pathway. Key miRNAs (rno-miR-665, rno-novel-108-mature, rno-novel-82-mature) demonstrated strong angiogenic associations in the ischemia-hypoxia model. CONCLUSIONS: This study delineates lncRNA, circRNA, and miRNA regulatory functions in ischemia-hypoxia through network construction, highlighting candidate therapeutic targets. These findings provide novel research directions for promoting angiogenesis and improving CIS prognosis.