Abstract
ObjectivesIn varicose veins, vascular smooth muscle cells (VSMCs) often shows phenotypic transition and abnormal proliferation and migration. Evidence suggests the FOXC2–Notch pathway may be involved in the pathogenesis of varicose veins. Here, this study aimed to explore the role of long non-coding RNA FOXC2-AS1 (FOXC2 antisense RNA 1) in phenotypic transition, proliferation, and migration of varicose vein-derived VSMCs and to explore whether the FOXC2-Notch pathway was involved in this process.MethodsThe effect of FOXC2-AS1 on the proliferation and migration of human great saphenous vein smooth muscle cells (SV-SMCs) was analyzed using MTT assay and Transwell migration assay, respectively. The levels of contractile marker SM22α and synthetic marker osteopontin were measured by immunohistochemistry and Western blot to assess the phenotypic transition.ResultsThe human varicose veins showed thickened intima, media and adventitia layers, increased synthetic VSMCs, as well as upregulated FOXC2-AS1 and FOXC2 expression. In vitro assays showed that FOXC2-AS1 overexpression promoted phenotypic transition, proliferation, and migration of SV-SMCs. However, the effect of FOXC2-AS1 overexpression could be abrogated by both FOXC2 silencing and the Notch signaling inhibitor FLI-06. Furthermore, FOXC2-AS1 overexpression activated the Notch pathway by upregulating FOXC2.ConclusionFOXC2-AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV-SMCs, at least partially, by activating the FOXC2-Notch pathway.
Highlights
Lower extremity varicose veins are a common disorder of venous dilation and tortuosity, and most varicose veins occur in the great saphenous vein [1, 2]
Varicose veins show upregulated forkhead box C2 (FOXC2)‐AS1 and FOXC2 expression The quantitative real-time PCR (qRT-PCR) results showed that FOXC2-AS1 expression in the varicose veins was significantly higher than that in the normal veins (Fig. 2a)
FOXC2‐AS1 overexpression promotes phenotypic transition, proliferation, and migration of SV‐SMCs We explored the effect of FOXC2-AS1 overexpression on phenotypic transition, proliferation, and migration of saphenous vein smooth muscle cells (SV-SMCs)
Summary
Lower extremity varicose veins are a common disorder of venous dilation and tortuosity, and most varicose veins occur in the great saphenous vein [1, 2]. The phenotypic transition of vascular smooth muscle cells (VSMCs) and the increased proliferation and migration are common pathophysiological processes of vascular remodeling-related diseases including varicose veins [3]. FOXC2 is one of the pathogenic genes most closely associated with the developmental defects and dysfunction of venous valves of the lower extremity [6,7,8]. The Notch pathway plays a key role in the development of vascular networks [10]. These findings collectively suggest the involvement of FOXC2-Notch pathway in the pathogenesis of varicose veins
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
