2023 Volume 64 Issue 3 Pages 470-482
Long noncoding RNAs (lncRNAs) can serve as treatment targets for abdominal aortic aneurysms (AAAs). Nonetheless, the exact role of FGD5 antisense RNA 1 (FGD5-AS1) in AAAs is unclear. Therefore, this study investigated the contribution of FGD5-AS1 to AAA growth regulated by vascular smooth muscle cells (VSMCs) and its potential mechanisms. ApoE-/- mice were used to establish the angiotensin II (Ang II)-elicited AAA model. RNA pull-down assay and dual luciferase reporter assay (DLRA) in human VSMCs were used in examining the interactions between FGD5-AS1 and its downstream proteins or miRNA targets. FGD5-AS1 expression in the mouse Ang II perfusion group was dramatically increased relative to the PBS-infused group. In the mouse AAA model, FGD5-AS1 overexpression induced SMC apoptosis, thereby promoting AAA growth. miR-195-5p acts as a potential FGD5-AS1 downstream target, whereas FGD5-AS1 promotes MMP3 expression by inhibiting miR-195-5p expression, thereby inhibiting proliferation and promoting apoptosis of smooth muscle cells. LncRNA FGD5-AS1 is detrimental to the proliferation and survival of SMCs during AAA growth. Therefore, FGD5-AS1 could be a novel treatment target for AAA.
