The active participation of p22phox-214T/C in the formation of intracranial aneurysm and the suppressive potential of edaravone

Abstract

Oxidative stress reactions play an important role in the pathogenesis of intracranial aneurysm (IA). p22phox is involved in the oxidative stress reaction, and it is a critical subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The present study investigated the association of genetic variants within the gene encoding p22phox-214T/C with IA. The p22phox-214T/C gene polymorphisms in 192 cases of IA and 112 controls were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mRNA expression of NADPH oxidase was also analyzed by RT-PCR. The results of RT-PCR were validated by ELISA. In a rabbit model of elastase-induced aneurysm, we used edaravone for anti-oxidative stress treatment to observe the curative effects. In the clinical cases, a significant difference in p22phox-214T/C allele frequencies in the IA group was observed compared with the control group (P<0.001). The expression level of NADPH oxidase was differed significantly between the IA group and the control group. In the rabbit model of elastase-induced aneurysm, the success rate of the aneurysmal model in the edaravone group and the wound ulcer rate were lower than those in the control group. In addition, the diameter of the aneurysm was smaller than in the edaravone group than in the control group (3.26±0.13 mm vs. 3.85±0.07 mm), and the expression of matrix metalloproteinase-9 (MMP-9) was significantly lower than that in the control group (P<0.0001). Thus, these data suggest the active participation of p22phox-214T/C in the formation of IA and the suppressive potential of edaravone against IA formation.