Cytokine Signaling and Matrix Remodeling Pathways Associated with Cardiac Sarcoidosis Disease Activity Defined Using...

Area of Science:

• Cardiology
• Immunology
• Proteomics

Background:

• Cardiac sarcoidosis (CS) diagnosis and risk assessment have improved with imaging, but treatments remain non-specific.
• Current treatment for CS often involves general heart failure therapies and broad anti-inflammatory approaches.
• There is a need for targeted inflammatory pathway identification in CS for improved therapeutic strategies.

Purpose of the Study:

• To conduct high-sensitivity plasma profiling of specific inflammatory and proteolytic pathways in patients with sarcoidosis and CS.
• To identify distinct inflammatory profiles associated with CS.
• To explore the role of cytokines, soluble cytokine receptors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) in CS.

Main Methods:

• Plasma samples were collected from 47 patients with biopsy-confirmed sarcoidosis (including 18 with CS) and 6 control subjects.
• High-sensitivity automated multiplex arrays were used to analyze cytokines, soluble cytokine receptors, MMPs, and TIMPs.
• F-18 fluorodeoxyglucose positron emission tomography was utilized for sarcoidosis patient assessment.

Main Results:

• Plasma levels of tumor necrosis factor (TNF), sCD30, and sTNFRI were elevated in sarcoidosis patients.
• Soluble interleukin sIL-2R and vascular endothelial growth factor receptors (sVEGFR2, sVEGFR3) showed the greatest increase in CS patients.
• MMP-9 increased in sarcoidosis but not CS, while TIMP levels decreased in both groups.

Conclusions:

• Increased activation of soluble cytokine receptors is a key finding in sarcoidosis and CS.
• These activated receptors contribute to inflammatory cell maturation and transmigration.
• The study highlights specific inflammatory signatures in CS, paving the way for more targeted therapies.