Suppression of neointimal hyperplasia following angioplasty-induced vascular injury in pigs infected with swinepox virus

Abstract

Many patients suffering from angina pectoris are treated with percutaneous coronary intervention (PCI) and quickly develop angiographic renarrowing, or restenosis, at the site of PCI treatment. Restenosis is thought to arise from the combinatorial activation of thrombotic and inflammatory responses. The inflammatory response responsible for restenosis is also thought to involve the activation of a cascade of serine proteases and its subsequent regulation. Poxviruses are known to possess a variety of immunomodulatory strategies, some of which target serine proteases, cytokines, and chemokines. To this end we evaluated whether systemic species-specific swinepox virus (SPV) infection could induce sufficient host-immune modulation to promote an anti-inflammatory and anti-proliferative effect, thereby preventing restenosis. Two groups of domestic feeder pigs were used - the first group was experimentally infected with SPV (n= 11) and the second group served as an uninfected control (n= 5). A week after infection, the pigs were anesthetized and percutaneous transluminal coronary angioplasty (PTCA) was performed in the left anterior descending coronary artery using X-ray fluoroscopy to visualize the balloon and record angiograms. Three weeks post infection, the pigs were euthanized and balloon angioplasty injured arteries were harvested and examined. We observed a statistically significant reduction of restenosis in SPV-infected pigs (p = 0.05) compared to control pigs and conclude that systemic swinepox virus infection causes sufficient host immune suppression to significantly reduce restenosis in pigs after balloon angioplasty injury.

Keywords: Coronary artery diseases; inflammation; neointimal proliferation; percutaneous transluminal coronary antioplasty; restenosis; swinepox virus..

Fig. (1)

Representative cross section of a LAD coronary artery from control/mock and SPV infected pigs. The arrowheads represent rupture sites made by the balloon over-inflation. These areas between arrowheads show neointimal cell proliferation, which is a main characteristic of the restenosis. Notice that degree of the neointimal cell proliferation in SPV-infected pig (a) differs from that of mock infected pigs (b). NI/M of SPV infected pigs = 0.88, NI/M of mock infected pigs = 1.11.