S100A1 is released from ischemic cardiomyocytes and signals myocardial damage via Toll-like receptor 4

Area of Science:

• Cardiology
• Immunology
• Molecular Biology

Background:

• S100 proteins act as alarmins, signaling danger and inflammation upon release from necrotic cells.
• S100A1 is the most abundant S100 isoform in cardiomyocytes.
• The role of S100A1 in myocardial infarction (MI) is not well understood.

Purpose of the Study:

• To investigate the role of S100A1 released from damaged cardiomyocytes during MI.
• To explore the effects of S100A1 on cardiac fibroblasts and its potential involvement in cardiac repair.

Main Methods:

• Measured S100A1 serum levels in patients with acute MI.
• Induced experimental MI in mice and assessed S100A1 release and internalization by cardiac fibroblasts (CFs).
• Conducted in vitro studies on CFs exposed to S100A1, analyzing signaling pathways (TLR4, MAP kinases, NF-κB) and phenotypic changes.
• Administered S100A1 intracardiacly in mice and used antibody neutralization to assess its impact on infarct size and cardiac function.

Main Results:

• S100A1 serum levels were significantly elevated in acute MI patients and in mice post-MI.
• S100A1 was internalized by CFs, activating TLR4-dependent signaling pathways.
• Exposure to S100A1 induced an immunomodulatory and anti-fibrotic phenotype in CFs, decreasing collagen and increasing ICAM1.
• Neutralization of S100A1 worsened cardiac function and increased infarct size post-MI.

Conclusions:

• S100A1 released from necrotic cardiomyocytes exhibits alarmin properties.
• Extracellular S100A1 may play a beneficial role in MI-related inflammation and cardiac repair.
• Further research is warranted to fully elucidate the therapeutic potential of S100A1 in MI.