Abstract
Vascular remodeling can be caused by angiotensin II type 1 receptor (AT1R) autoantibody (AT1-AA), although the related mechanism remains unknown. Angiotensin II type 2 receptor (AT2R) plays multiple roles in vascular remodeling through cross-talk with AT1R in the cytoplasm. Here, we aimed to explore the role and mechanism of AT2R 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 AT2R can promote VSMC migration in AT1-AA-induced vascular remodeling. Moreover, AT2R 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 AT2R expression by transcription factors, namely, a circular RNA and a microRNA, and showed that AT2R participated in AT1-AA-induced VSMC migration during the development of vascular remodeling. AT2R may be a potential target for the treatment of AT1-AA-induced vascular diseases.
Highlights
Vascular remodeling is closely related to various cardiovascular diseases, such as hypertension, atherosclerosis, and cardiomyopathy[1]
The cells treated with AT1-AA showed a stronger migratory ability than those treated with angiotensin II (Ang II), while IgG had no effect on cell migration (Fig. 1a and Supplementary Fig. S1a)
The results showed that actin filaments were recruited into thick, long actin bundles in the AT1-AA-treated cells, while no such phenomenon was observed in the Ang II treatment group (Fig. 1c)
Summary
Vascular remodeling is closely related to various cardiovascular diseases, such as hypertension, atherosclerosis, and cardiomyopathy[1]. The migration of vascular smooth muscle cells (VSMCs) from arterial media to intima plays a key role in the development of vascular remodeling because of its contribution to arterial intima thickening and lumen stenosis[2,3]. The renin-angiotensin system (RAS) is one of the major mediators of vascular remodeling and related diseases by regulating VSMC migration, promoting inflammation, etc.[4]. In addition to angiotensin II (Ang II), Ang II type 1 receptor (AT1R) autoantibody (AT1-AA) is a newly discovered agonist of AT1R5, which is involved in pathological changes in vascular diseases[6,7,8,9]. Ample evidence supports an important role for AT1-AA in vascular remodeling[11,12], the related molecular mechanism is not clear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
