CircPDS5B Reduction Improves Angiogenesis Following Ischemic Stroke by Regulating MicroRNA-223-3p/NOTCH2 Axis

Background and ObjectivesIschemic stroke (IS) is responsible for major causes of global death and disability, for which promoting angiogenesis is a promising therapeutic strategy. This study analyzed circular RNA PDS5B (circPDS5B) and its related mechanisms in angiogenesis in IS.MethodsIn the permanent middle cerebral artery occlusion (pMCAO) mouse model, circPDS5B, microRNA (miR)-223-3p, and NOTCH2 levels were checked. By testing neurologic function, neuronal apoptosis, and expression of angiogenesis-related proteins in pMCAO mice, the protective effects of circPDS5B knockdown were probed. In human brain microvascular endothelial cells (HBMECs) under oxygen-glucose deprivation (OGD) conditions, the effects of circPDS5B, miR-223-3p, and NOTCH2 on angiogenesis were studied by measuring cellular activities.ResultsThe increase of circPDS5B and NOTCH2 expression and the decrease of miR-223-3p expression were examined in pMCAO mice. Reducing circPDS5B expression indicated protection against neurologic dysfunction, apoptosis, and angiogenesis impairment. For circPDS5B-depleted or miR-223-3p-restored HBMECs under OGD treatment, angiogenesis was promoted. MiR-223-3p inhibition–associated reduction of angiogenesis could be counteracted by knocking down NOTCH2. CircPDS5B depletion–induced angiogenesis in OGD-conditioned HBMECs was repressed after overexpressing NOTCH2.DiscussionIn IS, the expression of circPDS5B was upregulated, and miR-223-3p inhibited HBMECs activity and promoted NOTCH2 expression, thus promoting IS. CircPDS5B reduction improves angiogenesis following ischemic stroke by regulating microRNA-223-3p/NOTCH2 axis.