STAT3 Contributes to Intracranial Aneurysm Formation and Rupture by Modulating Inflammatory Response

Area of Science:

• Vascular Biology
• Neuroscience
• Immunology

Background:

• Intracranial aneurysms (IA) are complex cerebrovascular diseases often linked to inflammatory processes.
• The precise molecular mechanisms driving IA pathogenesis, particularly the role of inflammatory signaling, require further elucidation.

Purpose of the Study:

• To investigate the role of Signal transducer and activator of transcription 3 (STAT3) in the formation of intracranial aneurysms.
• To determine the association between STAT3 expression, inflammatory responses, and clinicopathological features of IA.

Main Methods:

• Quantitative analysis of STAT3 expression in normal, unruptured, and ruptured IA tissues using RT-PCR and Western blot.
• Measurement of inflammatory cytokine levels via ELISA in IA tissues and cultured cells with manipulated STAT3 levels.
• Assessment of phenotypic modulation-related factors in VSMCs with altered STAT3 expression via RT-PCR.

Main Results:

• STAT3 expression was significantly upregulated in ruptured IA tissues, correlating with IA diameter and type.
• Increased secretion of inflammatory cytokines was observed in ruptured IA samples and positively associated with STAT3 levels.
• STAT3 overexpression enhanced the expression of smooth muscle cell markers (SM-α actin, SM-MHC) and matrix metalloproteinases (MMP2, MMP9), alongside increased inflammatory cytokine release.

Conclusions:

• STAT3 is identified as a critical regulator in the pathogenesis of intracranial aneurysms.
• STAT3 modulates IA formation, likely through its influence on inflammatory cytokine expression and vascular smooth muscle cell phenotype.