Abstract
Circular RNAs (circRNAs) have been shown to be associated with cardiac fibrosis. Atrial fibrosis is an important pathophysiological event in the progression of atrial fibrillation (AF). Although a novel circRNA calmodulin binding transcription activator 1 (circCAMTA1) has been reported to be related with the development of AF, the detailed molecular mechanisms remain largely unknown. In this study, we found that circCAMTA1 was upregulated in atrial muscle tissues of AF patients and angiotensin-II (Ang-II)-treated human atrial fibroblasts (HAFs). Moreover, circCAMTA1 expression was positively correlated with the expression of collagen (I and III) and α-SMA in atrial muscle tissues of AF patients. In vitro experiments, knockdown of circCAMTA1 significantly suppressed Ang-II-induced HAFs proliferation and reduced the expression of atrial fibrosis-associated genes, but overexpression of circCAMTA1 exhibited opposite results. In vivo experiments, circCAMTA1 knockdown ameliorated Ang-II-induced atrial fibrosis by reducing AF incidence, AF duration, and collagen synthesis. Functionally, circCAMTA1 facilitated Ang-II-induced atrial fibrosis in vitro and in vivo via downregulating the inhibitory effect of miR-214-3p on transforming growth factor β receptor 1 (TGFBR1) expression. In conclusions, circCAMTA1 knockdown alleviated atrial fibrosis through downregulating TGFBR1 expression intermediated by miR-214-3p in AF, suggesting circCAMTA1/miR-214-3p/TGFBR1 axis may be a novel therapeutic target for AF treatment in clinic.
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LZ conceived and designed the study and wrote the manuscript. LZ, QL, and WZ conducted the experiments. WML provided experimental advice and revised the manuscript. WY, HYZ, and YHK provided experimental advice. All authors read and approved the final version of the manuscript.
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Zhang, L., Lou, Q., Zhang, W. et al. CircCAMTA1 facilitates atrial fibrosis by regulating the miR-214-3p/TGFBR1 axis in atrial fibrillation. J Mol Histol 54, 55–65 (2023). https://doi.org/10.1007/s10735-022-10110-9
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DOI: https://doi.org/10.1007/s10735-022-10110-9