Perivascular gene transfer of NADPH oxidase inhibitor suppresses angioplasty-induced neointimal proliferation of rat carotid artery.

Vascular stretch induces NADPH oxidase-derived superoxide anion (O2-), which has been implicated in hypertrophy and cell proliferation. We hypothesized that targeted delivery of an NADPH oxidase inhibitor to the adventitia would reduce stretch-induced vascular O2- and attenuate neointima formation. We designed a novel replication-deficient adenovirus containing a fibroblast-active promoter driving expression of NADPH oxidase inhibitory sequence gp91ds (Ad-PDGFbetaR-gp91ds/eGFP).

Novel NAD(P)H oxidase inhibitor suppresses angioplasty-induced superoxide and neointimal hyperplasia of rat carotid artery.

Neointimal proliferation occurring after vascular or endovascular procedures is a major complication leading to end-organ or limb ischemia. In experimental models, balloon injury has been shown to induce NAD(P)H oxidase to produce vascular superoxide anion (O2*-) production, which has been implicated in cell proliferation, but a direct link is still unclear. We postulated that inhibition of arterial NAD(P)H oxidase, resulting in decreased O2*-, would lessen the neointimal hyperplasia caused by balloon injury to the common carotid artery (CCA).