Collagen synthesis and breakdown in the maintenance of the integrity of the fibrous cap

Illustration emphasizes the importance of collagen synthesis and breakdown in the maintenance of the integrity of the fibrous cap. Vascular smooth muscle cells synthesize essential extracellular matrix proteins such as collagen and elastin from amino acids. This process may be inhibited by interferon-γ (IFN-γ) secreted by activated T cells, thereby disrupting collagen synthesis, which may interfere with the maintenance and repair of collagen framework supporting the fibrous cap. Importantly, the expression of CD40 ligand on T cells may promote tissue proteolysis through the release and activation of matrix-degrading enzymes produced by vascular smooth muscle cells and inflammatory macrophages. Activated macrophages within the fibrous cap can secrete tissue proteases that facilitate the breakdown of collagen and elastin to peptides and amino acids. The loss of structural molecules provided by the extracellular matrix can thin and weaken the fibrous cap, rendering it particularly susceptible to rupture, which can manifest as acute coronary syndromes. Additional factors involved in the activation of macrophages include tumor necrosis factor-α (TNF-α), macrophage colony-stimulating factor (M-CSF), and macrophage chemoattractant protein-1 (MCP-1), among others. Microcalcifications located at high areas of strain in the thin and weak fibrous cap may initiate rupture of the plaque.