Right ventricular protein expression profile in end-stage heart failure

Area of Science:

• Cardiovascular Biology
• Proteomics
• Human Heart Failure Research

Background:

• The proteome of the right ventricle (RV) in human heart failure (HF) remains largely uncharacterized.
• Understanding RV proteomic differences compared to the left ventricle (LV) is crucial for comprehending HF pathophysiology.

Purpose of the Study:

• To compare the proteomes of the RV and LV in explanted human hearts with HF.
• To investigate proteomic differences within the RV based on ischemic versus non-ischemic etiology.
• To explore correlations between messenger RNA (mRNA) and protein expression in the RV.

Main Methods:

• Utilized 2D differential in-gel electrophoresis and liquid chromatography-tandem mass spectrometry to analyze RV and LV proteomes.
• Employed Western blotting and multiple-reaction monitoring for protein validation.
• Conducted RNA sequencing to assess mRNA and protein expression correlations.

Main Results:

• Identified 11 differentially expressed proteins between RV and LV in all HF hearts.
• Found distinct proteomic profiles in non-ischemic RVs compared to ischemic RVs, involving 7 proteins and networks related to hemostasis and atherosclerosis.
• Observed no significant proteomic differences based on RV echocardiographic function.
• Demonstrated inconsistent correlation between mRNA and protein expression, indicating post-transcriptional regulation.

Conclusions:

• Significant proteomic disparities exist between RV and LV in human HF, affecting contractile, cytoskeletal, metabolic, signaling, and survival pathways.
• RV proteome is influenced by HF etiology (ischemic vs. non-ischemic).
• Post-transcriptional regulation plays a critical role in RV protein expression in HF.