Abstract 1033: Heme Oxygenase-1 Alleviates Vascular Senescence through Inhibition of NAD(P)H Oxidase /NFkB Pathway
Heme oxygenase is a microsomal enzyme that catalyzes the degradation of heme into biliverdin, which is subsequently reduced to bilirubin, free iron and carbon monoxide (CO). Induction of heme oxygenase-1 (HO-1) has been potentially associated with cellular protection, especially against oxidative insults. In this study, using smooth muscle cell-directed HO-1 over-expression mice (HO-1 Tg), we investigated anti-aging effect of HO-1 on cardiovascular system in aged mouse. Senescence-associated beta-gal staining revealed that vascular senescence was enhanced in aorta of 52-week-old wild type mice (Wt), which is accompanied with increased expression of inflammatory cytokines and reduced eNOS expression determined by immunohistochemistry (IHC), as compared with those of age-matched HO-1 Tg. Western analysis and IHC for NADPH oxidase of aorta indicated that protein amounts of gp91phox and translocation to membrane fraction of p67phox were enhanced in aorta of Wt with reduced phosphorylation of Akt and telomerase activity. Furthermore, translocation of p65 to nuclei of medial smooth muscle cells is detected by IHC, indicating activation of NFkB pathway. In contrast, there are no significant changes in these senescence-related markers in age-matched HO-1 Tg. Taken together, these findings indicate that vascular HO-1 counteracts vascular senescence through inhibition of NADPH oxidase /NFkB pathway in aorta. Vascular HO-1 can be a new therapeutic target against aging.