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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:661.)
© 2003 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Enzymatically Modified LDL Induces Cathepsin H in Human Monocytes

Potential Relevance in Early Atherogenesis

Shan-Rui Han; Arash Momeni^*; Katharina Strach^*; Prapat Suriyaphol; Dominic Fenske; Kerstin Paprotka; Shin Ichi Hashimoto; Michael Torzewski; Sucharit Bhakdi; Matthias Husmann

From the Institute of Medical Microbiology and Hygiene and Department for Clinical Chemistry and Laboratory Medicine (M.T.), Johannes Gutenberg-University Mainz, Germany, and Department of Molecular and Preventive Medicine and CREST (S.I.H.), School of Medicine, University of Tokyo, Japan.

Correspondence to M. Husmann, Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany. E-mail MattHusmann{at}web.de

Objective— Modification with proteases and cholesterylesterase transforms LDL to a moiety that resembles lipoproteins isolated from atherosclerotic lesions and possesses atherogenic properties. To identify changes in monocyte-derived foam cells laden with enzymatically modified LDL (E-LDL), we compared patterns of the most abundant transcripts in these cells after incubation with LDL or E-LDL.

Methods and Results— Serial analyses of gene expression (SAGE) libraries were constructed from human monocytes after treatment with LDL or E-LDL. Several tags were differentially expressed in LDL-treated versus E-LDL–treated cells, whereby marked selective induction by E-LDL of cathepsin H was conspicuous. We show that cathepsin H is expressed in atherosclerotic lesions in colocalization with E-LDL. Furthermore, we demonstrate that LDL modified with cathepsin H and cholesterylesterase can confer onto LDL the capacity to induce macrophage foam cell formation and to induce cathepsin H.

Conclusions— Cathepsin H could contribute to the transformation of LDL to an atherogenic moiety; the process might involve a self-sustaining amplifying circle.

Key Words: enzymatically modified LDL • monocytes • foam cells • cathepsin H

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