Cardiac Proteome Profiling in Ischemic and Dilated Cardiomyopathy Mouse Models

Area of Science:

• Cardiovascular Biology
• Proteomics
• Molecular Medicine

Background:

• Heart failure (HF) presents a global health challenge with significant morbidity and mortality.
• Understanding the underlying pathophysiological mechanisms is crucial for developing effective prevention and personalized therapies for HF.

Purpose of the Study:

• To investigate and compare the proteomic profiles of mouse models with ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM).
• To identify differentially expressed proteins and pathways involved in the pathogenesis of different HF types.

Main Methods:

• Established mouse models for ICM (myocardial infarction) and DCM (Coxsackievirus B3 infection).
• Utilized quantitative proteomics (isobaric tags for relative and absolute quantitation, LC-MS/MS) to analyze protein expression in control and failing hearts.
• Performed bioinformatics analyses (Gene Ontology, KEGG, Ingenuity Pathway Analysis) to interpret proteomic data.

Main Results:

• Identified 1,638 proteins, with 286 differentially expressed between control and failing hearts.
• Commonly modulated pathways in both ICM and DCM included oxidative phosphorylation, metabolism, and protein folding.
• Distinct proteomic differences were observed between ICM and DCM, particularly in oxidative phosphorylation, metabolic, and AMPK signaling pathways.
• Confirmed down-regulation of SDHB and up-regulation of UQCRQ, GLUT4, and adiponectin in specific HF models.
• Observed decreased adenosine triphosphate (ATP) levels and differential regulation of phospho-AMPKα in ICM and DCM hearts.

Conclusions:

• Oxidative phosphorylation, cardiac metabolism, and protein folding are critical in HF pathogenesis.
• The distinct proteomic profiles between ICM and DCM underscore the heterogeneity of heart failure.
• Detailed proteomic analysis provides a foundation for developing more targeted therapeutic strategies for diverse HF etiologies.