Extracellular Matrix Alterations in Chronic Ischemic Cardiomyopathy Revealed by Quantitative Proteomics

Area of Science:

• Cardiovascular Biology
• Proteomics
• Extracellular Matrix Research

Background:

• Ischemic cardiomyopathy (ICM) leads to heart failure via cardiac extracellular matrix (ECM) remodeling.
• ECM deposition initially adaptive, becomes maladaptive, worsening cardiac remodeling and fibrosis.
• The precise ECM composition in ICM is not well-defined, hindering targeted therapies.

Purpose of the Study:

• To comprehensively profile the ECM proteome in end-stage ischemic cardiomyopathy.
• To identify specific ECM components and pathways altered in ICM.
• To uncover potential therapeutic targets for ICM-related heart failure.

Main Methods:

• Utilized sequential protein extraction with photocleavable surfactant Azo for ECM enrichment.
• Applied high-resolution mass spectrometry-based quantitative proteomics.
• Analyzed left ventricular tissues from ICM patients (n=16) and nonfailing donors (n=16).

Main Results:

• Identified and quantified over 6,000 protein groups, including 315 ECM proteins.
• Discovered significant upregulation of glycoproteins, proteoglycans, collagens, and ECM regulators in ICM.
• Noted differential expression of LOXL1, FBLN1, and VCAN; identified enhanced TGFβ signaling, integrin adhesion, and complement activation.

Conclusions:

• Provided a detailed proteomic landscape of ECM alterations in end-stage ICM.
• Revealed molecular pathways driving persistent ECM deposition in failing hearts.
• Identified novel molecular targets for therapeutic intervention in ischemic cardiomyopathy.