The circular RNA circHIPK3 plays a role in diabetic retinopathy by blocking miR-30a function, leading to increased endothelial proliferation and vascular dysfunction. These data suggest that circular RNA is a potential target to control diabetic proliferative retinopathy.
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.
H ypertension is a risk factor for several systematic diseases, such as stroke, myocardial infarction, coronary artery disease, and heart failure.1 Vascular remodeling contributes to increased peripheral resistance, affecting both the development and complications of hypertension. Vascular remodeling is an active process of structural changes that involves changes in cellular processes, including growth, apoptosis, migration, inflammation, and production of extracellular matrix proteins. Physiological remodeling is an adaptive response in response to hemodynamic changes and ageing. When this process becomes maladaptive, vascular remodeling contributes to end-organ damage in hypertension and its complications.2,3 Thus, a rationale for the regression of vascular remodeling becomes a therapeutic aim for treating hypertension-related vascular diseases.Long noncoding RNAs (lncRNAs) are noncoding transcripts >200 nucleotides in length. They regulate gene expression at transcriptional, post-transcriptional, and translational levels. 4,5 Increasing studies have revealed that lncRNAs regulate many biological processes, including gene expression, dosage compensation, genomic imprinting, and nuclear-cytoplasmic trafficking. 6 LncRNAs play important roles in tissue homeostasis and pathological conditions. 7 In vascular system, endothelial-expressed lncRNAs regulate vessel growth and function, such as metastasis associated lung adenocarcinoma transcript 1, 8 myocardial infarction associated transcript 9 and tyrosine kinase containing immunoglobulin and epidermal growth factor homology domain-1 antisense transcript.10 Smooth muscle-expressed lncRNAs regulate vascular smooth muscle cell (VSMC) proliferation, migration, and phenotypic switching.11,12 Hypertension is usually characterized by abnormal vascular tone, which is regulated by vascular smooth muscle-mediated vessel contraction and endothelium-dependent vessel vasodilation. 13,14 We speculated that lncRNAs might regulate vascular tone via affecting endothelial cell (EC) and VSMC function.lncRNA, growth arrest-specific 5 (GAS5), is widely expressed in adult tissues and over embryonic development. 15GAS5 was originally isolated from NIH 3T3 mouse embryonic fibroblast cells by subtraction hybridization.16 GAS5 plays important roles in several biological processes, including cell growth arrest, cell proliferation, and apoptosis. 17,18 Hypertension is tightly associated with the dysfunction of ECs and VSMCs. We speculated that abnormal GAS5 expression might alter EC and VSMC function, ultimately affecting the development of hypertension. GAS5 is composed of 12 exons, Abstract-Vascular remodeling is an important pathological feature of hypertension, leading to increased vascular resistance and reduced compliance. Endothelial cell (EC) and vascular smooth muscle cell (VSMC) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of EC and VSMC function. Herein, we determined whether long noncoding RNA-growth arrest-specific 5 (GAS5) is invo...
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