CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke

作者：Yanfang Liu, Yufeng Li, Yufeng Li, Tianyuan Zhang, Tianyuan Zhang, Yaojie Li, Yaojie Li, Zefeng Tan, Dan Ma, Yusheng Zhang, Shiyong Wang, Yusheng Zhang, Lian Huang, Yousheng Wu, Xuanlin Su, Zean Weng, Die Deng, Chi Kwan Tsang, Anding Xu, Dan Lu · 发表于：Circulation Research · 年份：2022 · DOI：10.1161/circresaha.121.319412 · 被引用次数：133 · 研究领域：Circular RNAs in diseases、Extracellular vesicles in disease、Kruppel-like factors research

Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking. We aim to investigate whether the CircOGDH (circular RNA derived from oxoglutarate dehydrogenase) is a potential biomarker for penumbra in patients with AIS and its role in ischemic neuronal damage. Methods: CircOGDH was screened from penumbra of middle cerebral artery occlusion mice and was assessed in plasma of patients with AIS by quantitative polymerase chain reaction. Magnetic resonance imaging was used to examine the penumbra volumes. CircOGDH interacted with miR-5112 (microRNA-5112) in primary cortical neurons was detected by fluorescence in situ hybridization, RNA immunoprecipitation, and luciferase reporter assay. Adenovirus-mediated CircOGDH knockdown ameliorated neuronal apoptosis induced by COL4A4 (Gallus collagen, type IV, alpha IV) overexpression. Transmission electron microscope, nanoparticle tracking analysis, and Western blot were performed to confirm exosomes. Results: CircOGDH expression was dramatically and selectively upregulated in the penumbra tissue of middle cerebral artery occlusion mice and in the plasma of 45 patients with AIS showing a 54-fold enhancement versus noncerebrovascular disease controls. Parti...