Heme oxygenase-1 gene therapy for prevention of vasospasm in rats

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Abstract
Object. Hemoglobin causes contraction of cerebral arteries and is also believed to cause vasospasm after subarachnoid hemorrhage (SAH). The goal in this study was to determine if overexpression of heme oxygenase-1 (HO-1), the principal enzyme involved in the metabolism of hemoglobin, would reduce contractions of cerebral arteries brought on by hemoglobin and decrease vasospasm after experimental SAH. Methods. Injection of adenovirus expressing HO-1 (Ad5HO-1) into the cisterna magna of rats produced a significant increase in expression of HO-1 messenger RNA, and protein and HO-1 activity in the basilar artery ([BA]; p < 0.05 for each measure compared with vehicle and/or control virus, according to analysis of variance or unpaired t-test). Injection of adenovirus expressing β-galactosidase (Ad-βGal) produced only mild, statistically nonsignificant increases. The HO-1 immunoreactivity was localized to the BA adventitia after injection of Ad5HO-1 or Ad-βGal. Injection of Ad5HO-1 and Ad-βGal increased the base...