Integrated proteomics reveals alterations in sarcomere composition and developmental processes during postnatal swine...

Area of Science:

• Cardiovascular Biology
• Proteomics
• Developmental Biology

Background:

• Neonatal swine hearts exhibit endogenous cardiac regeneration via cardiomyocyte proliferation.
• This regenerative capacity diminishes shortly after birth.
• The link between postnatal development and mammalian heart regeneration is not fully understood, particularly regarding proteomic changes.

Purpose of the Study:

• To comprehensively define the dynamic swine cardiac proteome during postnatal maturation.
• To identify proteomic alterations associated with the loss of cardiac regenerative capacity.
• To provide insights for developing novel therapeutic strategies for heart failure.

Main Methods:

• Integrated targeted "top-down" and global "bottom-up" proteomic workflows.
• Utilized quantitative proteomics to analyze protein abundance and alterations.
• Mapped identified proteins to developmental and metabolic processes.

Main Results:

• Identified significant alterations in sarcomere composition using top-down proteomics.
• Revealed proteoform landscape changes in sarcomeres, crucial for cardiomyocyte proliferation.
• Quantified global protein abundance changes, identifying over 700 differentially expressed proteins.
• Mapped proteins to shifts in developmental and metabolic pathways.

Conclusions:

• The swine cardiac proteome undergoes dynamic changes during postnatal development, correlating with the loss of regenerative capacity.
• Understanding these proteomic shifts provides crucial insights into the mechanisms of cardiac regeneration.
• These findings can guide future research towards novel therapeutic approaches for heart failure.