Background The crucial role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in regulating aneurysm formation, inflammation, and neural dysfunction has gradually been recognized. This study aimed to evaluate the effects of MALAT1 modification on pathological changes, inflammation, vascular smooth muscle cell (VSMC) phenotype switching, and the underlying mechanism in intracranial aneurysms (IAs). Methods MALAT1-overexpressing (oeMALAT1), MALAT1 short hairpin (shMALAT1), and semaphorin 3C (SEMA3C)-overexpressing (oeSEMA3C) lentiviruses were transfected alone or in combination into basilar artery VSMCs originating from IA rats. These lentiviruses were then stereotactically injected into IA rats. Results In vitro , the overexpression of MALAT1 inhibited cell proliferation while promoting cell apoptosis and invasion; the release of TNF-α, IL-1β, and IL-6; and the transformation of IA basilar artery VSMCs from the contractile type to the synthetic type. However, the silencing of MALAT1 had the opposite effect. The silencing of MALAT1 downregulated SEMA3C, and its silencing inactivated the Smad pathway. Furthermore, SEMA3C overexpression attenuated the effects of MALAT1 silencing on IA basilar artery VSMC proliferation, apoptosis, invasiveness, proinflammatory cytokines, phenotype switching, and Smad pathway inactivation. In vivo , silencing MALAT1 reduced the release of TNF-α, IL-1β, and IL-6, decreased pathological progression, inhibited VSMC synthetic type switching, and inactivated the Smad pathway in IA rats. However, the overexpression of SEMA3C reversed these effects. Conclusion Silencing MALAT1 represses pathological progression, inflammation, and VSMC phenotype switching by regulating the SEMA3C-mediated Smad pathway in IA.
Kang et al. (Wed,) studied this question.