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

Abstract

Background and objectives: Ischemic 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.

Methods: In 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.

Results: The 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.

Discussion: In 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.