Specific Nox components mediate the age‐related impairment in collateral growth

Collateral growth (CG) is impaired by aging, but the impairment is reversed by antioxidant treatment. The aim of this study was to determine if NADPH oxidase (Nox) mediated the age‐related impairment of CG. CG (% luminal expansion) and Nox expression were assessed with an established model of ileal artery ligation in young (2–3 mo; Y) and retired breeder (10–12 mo; RB) Wistar Kyoto (WKY) rats, as well as RB treated with p22 phox siRNA (RB+siRNA) or the Nox2 peptide inhibitor Nox2ds‐tat (RB+dstat). CG capacity at 7 days post ligation was restored in RB+siRNA (49.2±8.3%, p<0.001 vs. control) and in RB+ds‐tat (26.6±4.5%, p<0.003 vs. control), verifying the role of Nox in CG impairment. Measurement of Nox subunit basal mRNA expression with qPCR showed that Nox4 and p47 phox , but not Nox2, were significantly (p<0.05) increased compared to Y WKY. Nox1 expression was too low for quantification. Changes in RB collateral artery Nox expression at 1, 3, and 7 days relative to same‐animal control arteries are shown in the table. The results suggest an important role for specific Nox isoforms/subunits in age‐related CG impairment, and the inhibitor data implicate the Nox2 isoform as a primary mediator of CG impairment. Support: HL092012