Enzymatically modified LDL induces cathepsin H in human monocytes: potential relevance in early atherogenesis.
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.


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.
Han
Shan-Rui
SR
Institute of Medical Microbiology and Hygiene and Department for Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
Momeni
Arash
A
Strach
Katharina
K
Suriyaphol
Prapat
P
Fenske
Dominic
D
Paprotka
Kerstin
K
Hashimoto
Shin Ihi
SI
Torzewski
Michael
M
Bhakdi
Sucharit
S
Husmann
Matthias
M
D056655:Cathepsin H; D002403:Cathepsins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D015723:Gene Library; D006801:Humans; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000494:pharmacology*; D002787:Sterol Esterase / Q000494:pharmacology
D008077:Lipoproteins, LDL; D002784:Cholesterol; D002787:Sterol Esterase; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534126:CTSH protein, human; D056655:Cathepsin H