Table 2.

Rodent Models of Pulmonary Arterial Hypertension

Experimental Model	Species	Clinical and histopathological features
Classical models of PAH
Monocrotaline (MCT) 141-143	Rats (Mice)	In rats, initial mild endothelial injury and early influx of mononuclear inflammatory cells and vascular inflammation (Day 3-7), significant media remodeling and adventitia widening (Week 1-2) and low survival rate (Week 5 post MCT). No neointimal occlusive lesions. In mice less predictable effects.
Chronic Hypoxia 143-146	Rat Mice	In mice minimal vascular remodeling with mild neomuscularization and media thickening. In rats, more pronounced media remodeling but no intimal injury; younger animals more sensitive; distinct difference in gene expression induced by hypoxia between mice and rats. Animals partially or fully recover after re-exposure to normoxia.
New models of “human-like” PAH
VEGF antagonist SU5416 + Chronic Hypoxia 28,29,140	Rat	Development of severe and persistent PAH. Disease continues to progress after removing animals from hypoxic environment; precapillary occlusive endothelial proliferation and formation of plexiform lesions.
Monocrotalin + Unilateral Pneumonectomy 147-149	Rat	Media hypertrophy and formation of occlusive neointimal lesions. Younger rats develop perivasular proliferative lesions positive for VEGF receptor 2 and α–SM actin.
Genetically modified models of PAH
- Vasoactive intestinal peptide KO (VIP −/−) mouse150 - Overexpression of IL6 151 - Overexpression of S100A4 /Mits1 153,152 - Heterozygous BMPR2-mutant mice154	Mice	Develop PAH spontaneously or under hypoxia; not fully characterized models; neointimal injury and/or plexiform lesions present in some but not all models.
Endothelin B receptor deficient rat +MCT155	Rats	Occlusive neointimal lesions develop in distal pulmonary arteries