Experimental and transgenic models of pulmonary hypertension.

Pulmonary hypertension in human patients can result from increased pulmonary vascular tone, pressure transferred from the systemic circulation, dropout of small pulmonary vessels, occlusion of vessels with thrombi or intimal lesions, or some combination of all of these. Different animal models have been designed to reflect these different mechanistic origins of disease. Pulmonary hypertension models may be roughly grouped into tone-related models, inflammation-related models, and genetic models with unusual or mixed mechanism. Models of tone generally use hypoxia as a base, and then modify this with either genetic modifications (SOD, NOS, and caveolin) or with drugs (Sugen), although some genetic modifications of tone-related pathways can result in spontaneous pulmonary hypertension (Hph-1). Inflammation-related models can use either toxic chemicals (monocrotaline, bleomycin), live pathogens (stachybotrys, schistosomiasis), or genetic modifications (IL-6, VIP). Additional genetic models rely on alterations in metabolism (adiponectin), cell migration (S100A4), the serotonin pathway, or the BMP pathway. While each of these shares molecular and pathologic symptoms with different classes of human pulmonary hypertension, in most cases the molecular etiology of human pulmonary hypertension is unknown, and so the relationship between any model and human disease is unclear. There is thus no best animal model of pulmonary hypertension; instead, investigators must select the model most related to the specific pathology they are studying.