Circ_0092291 attenuates angiotensin II-induced cell damages in human aortic vascular smooth muscle cells via mediating the miR-626/COL4A1 signal axis.

Abstract

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, and the dysregulated circular RNAs (circRNAs) play key roles in AAA progression. Circ_0092291 was downregulated in AAA patients, but its function in AAA remains unclear. This research was performed for the functional analysis of circ_0092291 and its mechanism exploration with mircoRNA-626 (miR-626) and collagen type IV alpha1 chain (COL4A1) in AAA. Human aortic vascular smooth muscle cells (T/G HA-VSMC) were treated with angiotensin II (Ang II). Levels of circ_0092291, miR-626, and COL4A1 were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Inflammatory cytokines were examined by enzyme-linked immunosorbent assay (ELISA). Cell apoptosis was measured using caspase3 activity assay and flow cytometry. Angiopoiesis was assessed via tube formation assay. The protein analysis was conducted by western blot. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assays were used to validate the molecular binding. Circ_0092291 downregulation was found in AAA samples and Ang II-treated cells. Inflammatory response and cell apoptosis were reduced while angiopoiesis and ECM level were facilitated after overexpression of circ_0092291 in Ang II-treated T/G HA-VSMC cells. MiR-626 was a miRNA target for circ_0092291, and miR-626 inhibition protected T/G HA-VSMC from Ang II-induced cell injury. Moreover, the regulation of circ_0092291 was achieved by serving as a miR-626 sponge in Ang II-treated cells. COL4A1 was affirmed as a target for miR-626 and circ_0092291 resulted in the level change of COL4A1 by sponging miR-626. Additionally, miR-626 downregulation inhibited the cell damages caused by Ang II through increasing the level of COL4A1 and the function of circ_0092291 was attributed to the upregulation of COL4A1. The evidence indicated that circ_0092291 could suppress the Ang II-induced cell dysfunction by targeting the miR-626/COL4A1 signaling axis. Circ_0092291 might improve the diagnosis and treatment of AAA.Key Points.Biological mechanism, Apoptosis, Molecular target.