Fig. 6.

Schematic showing the mechanism of heme-induced platelet granule release. Heme activates multiple pathways of TLR4 signaling, which leads to the downstream phosphorylation of Akt at Ser473. Phosphorylated Akt(S473) inhibits mitochondrial complex V activity, resulting in the generation of mtROS which ultimately drive the release of TSP-1, IL1-β, PDGF-B, CXCL7, FGF basic and angiostatin from platelet α-granules.