Comparison of lung proteome profiles in two rodent models of pulmonary arterial hypertension

We studied the lung proteome changes in two widely used models of pulmonary arterial hypertension (PAH): monocrotaline (MCT) injection and chronic hypoxia (CH); untreated rats were used as controls ( n = 6/group). After 28 days, invasive right ventricular systolic pressure (RVSP) was measured. Lungs were immunostained for α‐smooth muscle actin (αSMA). 2‐DE ( n = 4/group) followed by nano‐LC‐MS/MS was applied for protein identification. Western blotting was used additionally if possible. RVSP was significantly increased in MCT‐ and CH‐rats (MCT 62.5 ± 4.4 mmHg, CH 62.2 ± 4.1 mmHg, control 25.0 ± 1.7 mmHg, p <0.001). This was associated with an increase of αSMA positive vessels. In both groups, there was a significantly increased expression of proteins associated with the contractile apparatus (diphosphoHsp27 ( p <0.001), Septin2 ( p <0.001), F‐actin capping protein ( p <0.01), and tropomyosin β ( p <0.02)). In CH, proteins of the nitric oxide (Hsc70; p = 0.002), carbon monoxide (biliverdin reductase; p = 0.005), and vascular endothelial growth factor (VEGF) pathway (annexin 3; p <0.001) were significantly increased. In MCT, proteins involved in serotonin synthesis (14‐3‐3; p = 0.02), the enhanced unfolded protein response (ERp57; p = 0.02), and intracellular chloride channels (CLIC 1; p = 0.002) were significantly elevated. Therefore, MCT‐ and CH‐induced vasoconstriction and remodeling seemed to be mediated via different signaling pathways. These differences should be considered in future studies using either PAH model.