P.Yiu, D.Rees*, W.Pugsley, J.McEwan.

Cardiovascular Repair and Remodelling Group (The Hatter institute), University College Hospital; and *Cruciform Project, UCL, London.Angioplasty restenosis and late vein graft failure are both characterised by the formation of a substantial neontima. Nitric oxide (NO) has been implicated in influencing the neointimal reponse due to its ability to inhibit platelet, leukocyte activation and smooth muscle cell proliferation in culture. However, the relative importance of NO in the neointimal response in vivo remains to be substantiated. Genetic knockout mice provide a tool to examine the role of a single gene in disease processes. We have developed a novel, reproducible mouse model for inducing neointimal lesions. It employs a fine tungsten wire to create microscopic lacerations in the carotid artery from the endolumenal aspect. Two weeks post-surgery, neointimal thickenings are localised to regions of injury and the lesion size is directly related to the depth and circumference of the lacerations. This technique was used to compare the neointimal response between inducible NO (iNOS) knockout mice and their strain controls. In mice deficient in iNOS, the injured carotid artery was smaller, as determined by the cross-sectional area bounded by the external elastic lamina (EEL), but exhibited a more exuberant neointimal thickening. Thus, we present here direct evidence that iNOS play a significant role in controlling the neointimal response as well as in vessel remodelling following injury in vivo.