on February 27, 2003
Published online before print February 27, 2003, doi: 10.1161/01.ATV.0000063614.21233.BF
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Submitted on December 17, 2002
Accepted on January 20, 2003
Enzymatically Modified LDL Induces Cathepsin H in Human Monocytes. Potential Relevance in Early Atherogenesis
Shan-Rui Han ;
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.
* To whom correspondence should be addressed. 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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