A review of genetically-driven rodent models of pulmonary hypertension

An increasing number of models used to examine the role of particular signaling pathways in vasculature and the development of pulmonary hypertension (PH) are based on animals with different genetic modifications. The present study explores the severity of PH-related lesions that can be provided by a genetic particular model in accordance to the most common non-genetic PH inducers such as chronic exposure to hypoxia or single injection of monocrotaline. A review of 516 interventions on a variety of animal models was performed. It examined the advantages of various genetically-driven procedures intended to develop spontaneous PH, and the effects of combining such procedures with common PH models or other stimuli ('second-hit') with the aim of exacerbating pulmonary artery remodeling, right ventricle hypertrophy and hemodynamics or animal mortality. A wide range of genetically-modified rodents are used for pre-clinical studies on PH, with different response to the genetic modification as compared to the most common non-genetic stimuli. Nevertheless, they could highlight the mechanisms and pathways that contribute to the expression of pathophysiological features of the disease, and they could be helpful in the identification of additional targets for new drugs.