Most of inflammatory cell infiltrate is comprised of monocyte-derived macrophages and foam cells and to a lesser extent it contains activated T lymphocytes and degranulated and activated mast cells. Thinning of the cap is a prelude to its subsequent rupture. Matrix dysregulation can contribute to thinning of the cap, as it is predominantly comprised of collagen and other matrix proteins. A combination of reduced matrix synthesis, with smooth muscle cell the primary responsible cell, and increased matrix breakdown, with monocyte macrophage the primary responsible cell, comprise this dysregulation. Evidence of ongoing collagen breakdown has been shown by Libby, supporting the hypothesis that there is increased collagen breakdown in the lipid rich vulnerable atherosclerotic lesions.
Serine proteases such as cathespin-S are also present in human atherosclerotic lesions.
The proteases are predominantly produced by the macrophage and foam cells in the lesions, and to a lesser extent by the smooth muscle cells and endothelial cells lining the microvasculature. PAGE TOP Potential mediators of MMP expression MMP gene expression in the macrophage and smooth muscle cell may be stimulated by a number of factors including oxidative stress. Low concentrations of oxidized LDL induce MMP gene expression in the macrophage. Cell-cell interaction activates T lymphocytes, particularly through ligation of CD 40 and through elaboration of interferon gamma, and may be mediators of MMP expression. Tenascin, an MMP produced by macrophages, is capable of inducing the MMP-9 gene in the macrophage, as shown by Shah.