Monocrotaline-induced pulmonary arterial hypertension in rats led to significant changes in left and right ventricular protein abundance linked to apoptosis, fibrosis, and structural remodeling.
Proteomic profiling of rat myocardium in monocrotaline-induced PAH reveals distinct early and late metabolic and structural protein alterations in both the right and left ventricles.
Absolute Event Rate: 50.5% vs 21.57%
p-value: p=<0.001
Abstract Pulmonary arterial hypertension (PAH) is a rare, fatal, and incurable disorder. Although advances in the understanding of the PAH pathobiology have been seen in recent years, molecular processes underlying heart remodelling over the course of PAH are still insufficiently understood. Therefore, the aim of this study was to investigate myocardial proteomic profile of rats at different stages of monocrotaline-induced PAH. Samples of left and right ventricle (LV and RV) free wall collected from 32 Wistar rats were subjected to proteomic analysis using an isobaric tag for relative quantitation method. Hemodynamic parameters indicated development of mild elevation of pulmonary artery pressure in the early PAH group (27.00 ± 4.93 mmHg) and severe elevation in the end-stage PAH group (50.50 ± 11.56 mmHg). In early PAH LV myocardium proteins that may be linked to an increase in inflammatory response, apoptosis, glycolytic process and decrease in myocardial structural proteins were differentially expressed compared to controls. During end-stage PAH an increase in proteins associated with apoptosis, fibrosis and cardiomyocyte Ca 2+ currents as well as decrease in myocardial structural proteins were observed in LV. In RV during early PAH, especially proteins associated with myocardial structural components and fatty acid beta-oxidation pathway were upregulated. During end-stage PAH significant changes in RV proteins abundance related to the increased myocardial structural components, intensified fibrosis and glycolytic processes as well as decreased proteins related to cardiomyocyte Ca 2+ currents were observed. At both PAH stages changes in RV proteins linked to apoptosis inhibition were observed. In conclusion, we identified changes of the levels of several proteins and thus of the metabolic pathways linked to the early and late remodelling of the left and right ventricle over the course of monocrotaline-induced PAH to delineate potential therapeutic targets for the treatment of this severe disease.
Hołda et al. (2020) studied Pulmonary arterial hypertension (n=66). Monocrotaline vs. Placebo (PBS medium) was evaluated on Right ventricular systolic pressure at end-stage PAH (mmHg) (p=<0.001). Monocrotaline-induced pulmonary arterial hypertension in rats led to significant changes in left and right ventricular protein abundance linked to apoptosis, fibrosis, and structural remodeling.