LPS induces RGS-1 to promote infectious intracranial aneurysm formation and rupture by accelerating smooth muscle cell phenotypic switching

Objective: Patients with infectious intracranial aneurysms (IIAs) have high mortality rates. Sepsis is an important condition that induces IIA. Smooth muscle cell (SMC) phenotypic switching may have a critical effect on sepsis- induced IIA, but its role remains unclear. Hence, we aimed to identify sepsis-induced target genes involved in SMC phenotypic switching and their underlying mechanisms.<br /> Methods and Results: RNA sequencing and bioinformatics analyses of samples from patients with intracranial aneurysms and sepsis identified RGS-1 as a common differentially expressed gene (DEG) involved in SMC phenotypic switching. Experimental verification demonstrated that lipopolysaccharide (LPS), a critical molecule in sepsis, increased RGS-1 levels, promoted SMC phenotypic switching and proliferation, and upregulated the expression of matrix metalloproteinases and inflammatory factors. Furthermore, qRT-PCR and immunofluorescence experiments confirmed that RGS-1 knockdown under LPS stimulation inhibited SMC phenotypic switching, cell proliferation, and decreases in matrix metalloproteinases and inflammatory factors. Mechanistically, western blotting, bioinformatics analyses, and chip assays revealed that RGS-1 activates the JNK-P38 pathway to promote SMC phenotypic switching and is regulated by the transcription factor STAT1. Conclusion: LPS induces RGS-1 to promote IIA formation and rupture by accelerating SMC phenotypic switching.