Metallothionein in human atherosclerotic lesions: a scavenger mechanism for reactive oxygen species in the plaque?

Abstract.

Oxidative stress is important in the genesis of atherosclerotic lesions. The extracellular effects of reactive oxygen species (ROS), such as oxidative modification of lipoproteins and upregulation of matrix degrading enzymes, are considered crucial in this context. The effects of ROS are counteracted by antioxidant scavenging systems; metallothioneins (MTs) may serve as such. This study was designed to see whether MTs occur in human atherosclerotic plaques and which cell types are involved. The immunohistochemical study focuses on smooth muscle cells (SMCs), macrophages, and T cells. MT immunoreactivity was seen only within SMCs, which occurred usually in small clusters and were found mostly near lipid cores and occasionally in the media. Double immunostaining showed MT-positive SMCs and matrix metalloproteinase (MMP)-9 in the same area but not within the same cell. Electron microscopy was done to evaluate the subtype of MT-positive cells and revealed that the majority consisted of synthetic SMCs. Thus, atherosclerotic plaques in humans contain MT known to act as a scavenger for ROS. The observation that MT was expressed only in SMCs, particularly those of synthetic phenotype, suggests that MT plays a role in protecting these active matrix-producing cells.