Strong induction of members of the chitinase family of proteins in atherosclerosis - Chitotriosidase and human cartilage gp-39 expressed in lesion macrophages

Atherosclerosis is initiated by the infiltration of monocytes into the sube ndothelial space of the vessel wall and subsequent lipid accumulation of th e activated macrophages. The molecular mechanisms involved in the anomalous behavior of macrophages in atherogenesis have only partially been disclose d. Chitotriosidase and human cartilage gp-39 (HC gp-39) are members of the chitinase family of proteins and are expressed in lipid-laden macrophages a ccumulated in various organs during Gaucher disease. In addition, as shown in this study, chitotriosidase and HC gp-39 can be induced with distinct ki netics in cultured macrophages. We investigated the expression of these chi tinase-like genes in the human atherosclerotic vessel wall by in situ hybri dizations on atherosclerotic specimens derived from femoral artery (4 speci mens), aorta (4 specimens), iliac artery (3 specimens), carotid artery (4 s pecimens), and coronary artery (1 specimen), as well as 5 specimens derived from apparently normal vascular tissue. We show for the first time that ch itotriosidase and HC gp-39 expression was strongly upregulated in distinct subsets of macrophages in the atherosclerotic plaque. The expression patter ns of chitotriosidase and HC gp-39 were compared and shown to be different from the patterns observed for the extracellular matrix protein osteopontin and the macrophage marker tartrate-resistant acid phosphatase. Our data em phasize the remarkable phenotypic variation among macrophages present in th e atherosclerotic lesion. Furthermore, chitotriosidase enzyme activity was shown to be elevated up to 55-fold in extracts of atherosclerotic tissue. A lthough a function for chitotriosidase and HC gp-39 has not been identified , we hypothesize a role in cell migration and tissue remodeling during athe rogenesis.