Abstract
Circular RNAs (circRNAs) have been implicated in the dysfunction of vascular smooth muscle cells (VSMCs), which is linked with the development of abdominal aortic aneurysm (AAA). Herein, we explored the precise action of circRNA fibronectin type III domain containing 3B (circ-FNDC3B) in VSMC injury triggered by angiotensin II (Ang-II).Circ-FNDC3B, microRNA (miR) -143-3p, and a disintegrin and metalloproteinase 10 (ADAM10) were quantified by quantitative real-time polymerase chain reaction or western blot assay. Ribonuclease R and subcellular localization assays were applied to characterize circ-FNDC3B. Cell viability, apoptosis, and proliferation were assessed by the Cell Counting Kit-8 assay, flow cytometry, and 5-Ethynyl-2' -Deoxyuridine assay, respectively. The levels of tumor necrosis factor alpha, interleukin-6, superoxide dismutase, and malonaldehyde were estimated by enzyme-linked immunosorbent assay. Direct relationship miR-143-3p and circ-FNDC3B or ADAM10 was verified by dual-luciferase reporter and RNA immunoprecipitation assays.Circ-FNDC3B was highly expressed in AAA tissues and Ang-II-treated VSMCs. Knocking down circ-FNDC3B alleviated Ang-II-induced VSMC injury. Mechanistically, circ-FNDC3B directly targeted miR-143-3p, and miR-143-3p was a downstream mediator of circ-FNDC3B in regulating cell injury induced by Ang-II. ADAM10 was directly targeted and inhibited by miR-143-3p. MiR-143-3p-mediated inhibition of ADAM10 relieved Ang-II-induced VSMC injury. Furthermore, circ-FNDC3B acted as a competing endogenous RNA for miR-143-3p to modulate ADAM10 expression.Our findings suggested that circ-FNDC3B silencing ameliorated cytotoxicity triggered by Ang-II in VSMCs at least partially depending on the regulation of the miR-143-3p/ADAM10 axis.