Using proteomics to identify protein changes in acute right ventricular pressure overload

Right ventricular (RV) failure from acute pressure overload (RVPO) is a common clinical problem. We previously showed 90 min RVPO without ischemia causes RV free wall (RVFW) dysfunction that persists after relief of RVPO. We used a proteomics approach to ascertain potential mechanisms for this dysfunction. Methods Anesthetized open‐chest pigs (n=12) underwent 90 min RVPO by pulmonary artery constriction (RV systolic pressure 62±1 mmHg) or SHAM RVPO (RVSP 27±1 mmHg) followed by 30 min recovery. RVFW contractility was assessed by sonomicrometry. Pooled RVFW biopsies from RVPO and SHAM were subjected to two‐dimensional difference gel electrophoresis (DIGE) to assess protein alterations following RVPO. Proteins with altered abundance were identified by MALDI‐TOF/MS peptide mass fingerprinting. Results RVPO caused severe RVFW dysfunction (62% fall in regional external work vs 17% fall in SHAM). DIGE demonstrated upregulation of oxidative metabolism enzymes, phosphorylation of HSP27 and αβ‐crystallin (proteins known to regulate actin dynamics), and a 36% decline in α‐1‐antichymotrypsin in RVPO vs SHAM (p<0.01). Results for protein changes were independently confirmed by immunoblotting. In addition, there was a 30% decline in the easily releasable myofilament pool in RVPO vs SHAM (p<0.01). Conclusions These data indicate that acute RVPO results in altered actin dynamics and myofibril stabilization. The decrease in α‐1‐antichymotrypsin suggests an as‐yet unidentified serine protease may be involved in the development of or response to contractile dysfunction in RVPO. Supported by Department of Veterans Affairs and NHLBI.