Human Animal Model
Group 1: PAH  
Early phase:
● Medical hypertrophy
● Cellular intimal proliferation of muscular pulmonary arteries
● Appearance of muscle in normally nonmuscular arteries
OVA/Asp challenge mice; Su/OVA rat
BMPR2 mutant mice; VIP-/- mouse
Su-Hx; CDH/PPHN baboon/lamb
MCT rat; Autoab transfer rat
S100A4/MTS-1 over expressing mouse
Fra2 Tg mouse; IL-6 over expressing mouse
Schisto mouse; Neprilysin null mouse
Late phase:
● Concentric laminar intimal fibrosis
● Loss of luminal vascular volume
● Dilatation lesions (vein-like branches, angiomatoid lesions)
● Plexiform lesions
● Recanalization of arteries
● Fibrinoid necrosis
● Arteritis
Broiler chicken
S100A4/MTS-1 over expressing mouse
MCT pneumonectomy rat
Group 1’: PVOD
● Foci of intense congestion of pulmonary parenchyma
● Patchy hemosiderosis associated with areas of congestion
● Encrustation of elastin with iron and calcium salts
● Duplication of elastic laminae
● Obliterative fibrosis of small veins/venules
● Abnormalities set against a background of near normal lung
● Prominence of capillaries
Group 1’: PCH
● Marked increase/prominence of capillary vessels in alveoli interlobular septa, bronchovascular bundles, and pleura; masses of capillaries may bulge into lumina of airways and vessels
● Associated features of PVOD in some cases
Group 2: Pulmonary hypertension with left heart disease
● Arterialization of large or middle-sized pulmonary veins
● Interstitial edema and fibrosis
● Hemosiderosis
● Medial hypertrophy/adventitial thickening of pulmonary arteries
Group 3: Pulmonary hypertension associated with lung disease and/or hypoxemia
3.1 and 3.3–3.5. Hypoxic pulmonary vasculopathy
● Muscularization of arterioles
● Medial hypertrophy of muscular pulmonary arteries
● Longitudinally oriented intimal smooth muscle cells
● Slight medial hypertrophy of veins
3.2. Pulmonary vasculopathy associated with interstitial lung disease
● Features of hypoxic pulmonary vasculopathy
● Eccentric intimal fibrosis of arteries and, to a lesser extent, veins
Broiler chicken
Chronic hypoxia-Neonatal calf
Su-Hx rat
Fawn Hooded rat
Chronic hypoxia-mouse
Chronic hypoxia-rat
Chronic hypoxia + MCT rat
Group 4: Pulmonary hypertension due to chronic thrombotic/embolic disease
● Thromboembolic obstruction of distal pulmonary arteries
Eccentric intimal fibrosis
Recanalized organized thrombi forming bands and webs
Fresh thrombi very rare
● Nonthrombotic pulmonary embolism
Nonthrombotic material (foreign body/bone marrow)
Fat embolism
Vena cava ligation + thrombi-pig, rat, primate
Vena cava ligation + stenosis-mouse, rat,
De-endothelialization + 50-80% jugular vein
Group 5: Miscellaneous [sarcoidosis, compression of pulmonary vessels (adenopathy), tumor, fibrosingmediastinitis]  
● Heterogeneous group of disorders, some showing features of congestive vasculopathy, some postthromboticvasculopathy  
Table 3: Correlation of Histopathological Features of Human Pulmonary Hypertensive Vascular Disease to Preclinical Models Human Animal Model