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TWIST1 silencing attenuates intracranial aneurysms by inhibiting NF-κB signaling


Deng Wang
Dan Lai
Chengfu Peng

Abstract

Purpose: To investigate the effect of Twist family basic helix-loop-helix transcription factor 1 (TWIST1) on intracranial aneurysms.
Methods: A rat model of intracranial aneurysm was established by ligating the posterior branches of both the renal and left common carotid arteries. Pathological changes in the intracranial arterial wall were investigated using hematoxylin-eosin staining. TWIST1 expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, while vascular smooth muscle cell apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Inflammation was evaluated using enzyme-linked immunosorbent assay (ELISA).
Results: Rats with intracranial aneurysms had degenerative changes in vessel wall structure. In
intracranial aneurysm rats, TWIST1 was upregulated in arterial wall sections, and TWIST1 knockdown ameliorated the pathological changes to the arterial wall. TWIST1 silencing reduced serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels and suppressed vascular smooth muscle cell apoptosis in rats with intracranial aneurysms. TWIST1 knockdown increased phospho (p)-inhibitor of nuclear factor-κB (IκB) and decreased IκB and p-p65 in intracranial aneurysm rat arterial wall sections.
Conclusion: In intracranial aneurysms, silencing TWIST1 promoted vascular remodeling and suppresses vascular smooth muscle cell apoptosis and inflammation through inactivating NF-κB
signaling, revealing TWIST1 silencing as a potential treatment strategy.


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996