Increased AT(2)R expression is induced by AT(1)R autoantibody via two axes, Klf-5/IRF-1 and circErbB4/miR-29a-5p, to promote VSMC migration

Vascular remodeling can be caused by angiotensin II type 1 receptor (AT(1)R) autoantibody (AT1-AA), although the related mechanism remains unknown. Angiotensin II type 2 receptor (AT(2)R) plays multiple roles in vascular remodeling through cross-talk with AT(1)R in the cytoplasm. Here, we aimed to explore the role and mechanism of AT(2)R in AT1-AA-induced vascular smooth muscle cell (VSMC) migration, which is a key event in vascular remodeling. In vitro and in vivo, we found that AT(2)R can promote VSMC migration in AT1-AA-induced vascular remodeling. Moreover, AT(2)R expression was upregulated via Klf-5/IRF-1-mediated transcriptional and circErbB4/miR-29a-5p-mediated posttranscriptional mechanisms in response to AT1-AA. Our data provide a molecular basis for AT1-AA-induced AT(2)R expression by transcription factors, namely, a circular RNA and a microRNA, and showed that AT(2)R participated in AT1-AA-induced VSMC migration during the development of vascular remodeling. AT(2)R may be a potential target for the treatment of AT1-AA-induced vascular diseases.