Proteomic Analysis of a Porcine Model of Pulmonary Arterial Hypertension Reveals Branched-Chain Amino Acids as a Possible Cause of Right Atrial Remodeling
Pulmonary arterial hypertension (PAH) is a rare disease characterized by decreased pulmonary vasculature compliance leading to pathophysiological remodeling of the right heart. Right atrial (RA) strain can detect disease progression before right ventricular dysfunction or clinical changes occur, but RA remodeling in PAH remains uncharacterized. A porcine model of PAH via pulmonary arterial banding (PAB) was compared to control animals using MRI-measured RA functional parameters paired with quantitative mass spectroscopy proteomics. PAB animals had RA dysfunction and dilation. Proteomic analysis of RA tissue identified down-regulation of branched-chain amino acid (BCAA) degradation in PAB pigs. RA BCAA concentrations were elevated in PAB pigs and correlated inversely with RA ejection fraction. RA remodeling due to elevated BCAAs may be mediated by transcription factor CREB, which has previously been implicated in cardiac hypertrophy. Impaired BCAA degradation increases RA BCAA levels, which correlate to worse RA function. Therefore, decreasing BCAA levels in PAH patients may have therapeutic effects specific to the RA.