Skip to main content
. 2014 May 15;6(6):778–794. doi: 10.15252/emmm.201303498

Figure 8. Simplified scheme illustrating S100A1's role in myocardial infarction.

Figure 8

1) Ischemic injury leads to the release of S100A1 from cardiomyocytes into the myocardial interstitium. 2) Extracellular S100A1 is specifically internalized by cardiac fibroblasts through clathrin- and caveolin-independent fluid endocytosis. 3) Endocytosed S100A1 binds to intracellular Toll-like receptor 4 (TLR4), thereby prompting trafficking to acidified endolysosomes. 4) MyD88 binds to the cytoplasmic domain of acidified TLR4 and initiates signal transduction. 5) The S100A1-TLR4-MyD88 signaling complex transiently activates MAPK/SAPK and NF-κB pathways. 6) S100A1-mediated signal transduction leads to an anti-fibrotic and immunomodulatory phenotype transition of cardiac fibroblasts. Neutralization of S100A1 resulted in significantly increased infarct size and impaired left ventricular function, suggesting a beneficial net effect of S100A1 in myocardial infarction.