Vascular dysfunction is a hallmark of ischemic, cancer, and inflammatory diseases, contributing to disease progression. Circular RNAs (circRNAs) are endogenous non-coding RNAs, which have been reported to be abnormally expressed in many human diseases. In this study, we used retinal vasculature to determine the role of circular RNA in vascular dysfunction. We revealed that cZNF609 was significantly up-regulated upon high glucose and hypoxia stress in vivo and in vitro. cZNF609 silencing decreased retinal vessel loss and suppressed pathological angiogenesis in vivo. cZNF609 silencing increased endothelial cell migration and tube formation, and protected endothelial cell against oxidative stress and hypoxia stress in vitro. By contrast, transgenic overexpression of cZNF609 showed an opposite effects. cZNF609 acted as an endogenous miR-615-5p sponge to sequester and inhibit miR-615-5p activity, which led to increased MEF2A expression. MEF2A overexpression could rescue cZNF609 silencing-mediated effects on endothelial cell migration, tube formation, and apoptosis. Moreover, dysregulated cZNF609 expression was detected in the clinical samples of the patients with diabetes, hypertension, and coronary artery disease. Intervention of cZNF609 expression is promising therapy for vascular dysfunction.

中文翻译：

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沉默环状RNA-ZNF609可改善血管内皮功能障碍

血管功能障碍是缺血性，癌症和炎性疾病的标志，导致疾病进展。环状RNA（circRNA）是内源性非编码RNA，据报道在许多人类疾病中它们均异常表达。在这项研究中，我们使用视网膜脉管系统来确定环状RNA在血管功能障碍中的作用。我们揭示了体内和体外高糖和低氧应激后cZNF609明显上调。cZNF609沉默减少视网膜血管丢失和抑制病理血管生成体内。cZNF609沉默可增加内皮细胞的迁移和管的形成，并在体外保护内皮细胞免受氧化应激和缺氧应激的影响。相比之下，cZNF609的转基因过表达表现出相反的作用。cZNF609充当内源性miR-615-5p海绵，隔离并抑制miR-615-5p活性，从而导致MEF2A表达增加。MEF2A过表达可以挽救cZNF609沉默介导的对内皮细胞迁移，管形成和凋亡的作用。此外，在患有糖尿病，高血压和冠状动脉疾病的患者的临床样品中检测到cZNF609表达失调。干预cZNF609表达是治疗血管功能障碍的有前途的疗法。