The most commonly used procedures to induce arterial injury in mice are carotid artery ligation with cessation of blood flow and mechanically-induced denudation of endothelium in the carotid or the femoral arteries. Both procedures result in neointimal hyperplasia after two to three weeks. A survey of various inbred strains of mice shows that strainspecific differences in susceptibility to injury-induced neointimal hyperplasia are different than those for susceptibility to diet-induced atherosclerosis, with strains identified as susceptible to both neointimal hyperplasia and atherosclerosis, resistant to both, susceptible to atherosclerosis but resistant to neointimal hyperplasia, or resistant to atherosclerosis but susceptible to neointimal hyperplasia. Inflammatory cells such as T and B lymphocytes, which are contributory to atherosclerosis, are protective against injury-induced neointimal hyperplasia. In contrast, the infiltration of monocytes into the site of injury and their differentiation to macrophages favor neointimal hyperplasia similar to their pathogenic role in atherosclerosis. The regulatory role of lymphocytes and macrophages in neointimal hyperplasia is related to the production of cytokines such as interferon-γ and tumor necrosis factor-α, respectively. Interestingly, inducible nitric oxide synthase (iNOS) activity appears to inhibit neointimal hyperplasia in the endothelial denudation model but contributes to neointimal hyperplasia when arterial injury is induced by periadventitial cuff placement. The difference appears to be due to the time required for endothelial recovery and the participation of inflammatory cells. Thus, although arterial injury-induced neointimal hyperplasia results in similar vascular occlusion as progressive atherosclerosis, the pathology and mechanism of the two disease processes are quite different.
Keywords: Neointimal hyperplasia, mouse genetics, nitric oxide, lymphocytes, smooth muscle cells, macrophages, bone marrow progenitor cells