Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
Published Online
on October 10, 2002

Arteriosclerosis, Thrombosis, and Vascular Biology. 2002
Published online before print October 10, 2002, doi: 10.1161/01.ATV.0000041405.07367.B5
A more recent version of this article appeared on December 1, 2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
22/12/2086    most recent
01.ATV.0000041405.07367.B5v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, M.
Right arrow Articles by Kovanen, P. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, M.
Right arrow Articles by Kovanen, P. T.
Related Collections
Right arrow Pathophysiology
Right arrow Cell biology/structural biology
Right arrow Lipid and lipoprotein metabolism

Submitted on May 27, 2002
Accepted on September 26, 2002

Mast Cell Tryptase Degrades HDL and Blocks Its Function as an Acceptor of Cellular Cholesterol

Miriam Lee ; Christian P. Sommerhoff ; Arnold von Eckardstein ; Frank Zettl ; Hans Fritz ; and Petri T. Kovanen *

From the Wihuri Research Institute (M.L., P.T.K.), Helsinki, Finland; Abteilung Klinische Chemie und Klinische Biochemie (C.P.S., F.Z., H.F.), Chirurgische Klinik und Poliklinik Innenstadt der LMU, München, Germany; and Institut für Klinische Chemie und Laboratoriumsmedizin (A.v.E.), Zentrallaboratorium, Westfälische Wilhelms-Universität Münster, Münster, Germany.

* To whom correspondence should be addressed. E-mail: petri.kovanen{at}wri.fi.

Objective—In human atherosclerotic lesions, degranulated mast cells are found in the vicinity of macrophage foam cells. Mast cell granules contain tryptase, a tetrameric serine protease requiring glycosaminoglycans for stabilization. No endogenous inhibitors have been described for tryptase, and the physiological functions of the enzyme are poorly understood. Here, we investigated the effects of human tryptase on the integrity of high density lipoprotein (HDL)3 and on its ability to release cholesterol from cultured mouse macrophage foam cells.

Methods and Results—Incubation of HDL3 with tryptase led to degradation of its apolipoproteins. Tryptase predominantly degraded a quantitatively minor subfraction of HDL3 that is lipid poor, exhibits electrophoretic pre-ß mobility, and contains either apolipoprotein A-I or apolipoprotein A-IV as its sole apolipoprotein. Moreover, tryptase caused functional changes in HDL3 by destroying its ability to promote high-affinity efflux of cholesterol from macrophage foam cells, ie, the pre-ß-HDL-dependent component of the process. Human aortic proteoglycans increased the ability of tryptase to proteolyze HDL3, suggesting that the proteoglycan-rich extracellular matrix of the arterial intima provides an appropriate environment for the extracellular actions of tryptase.

Conclusions—By depleting pre-ß-HDL, mast cell tryptase may impair the initial step of reverse cholesterol transport and will then favor cellular accumulation of cholesterol during atherogenesis.
Key words: tryptase • human mast cells • arterial proteoglycans • cholesterol efflux • HDL3




This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
M. A. Liz, C. M. Gomes, M. J. Saraiva, and M. M. Sousa
ApoA-I cleaved by transthyretin has reduced ability to promote cholesterol efflux and increased amyloidogenicity
J. Lipid Res., November 1, 2007; 48(11): 2385 - 2395.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Lee-Rueckert, R. Vikstedt, J. Metso, C. Ehnholm, P. T. Kovanen, and M. Jauhiainen
Absence of endogenous phospholipid transfer protein impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells
J. Lipid Res., August 1, 2006; 47(8): 1725 - 1732.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. Steffel, A. Akhmedov, H. Greutert, T. F. Luscher, and F. C. Tanner
Histamine Induces Tissue Factor Expression: Implications for Acute Coronary Syndromes
Circulation, July 19, 2005; 112(3): 341 - 349.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
W. Verreth, D. De Keyzer, M. Pelat, P. Verhamme, J. Ganame, J. K. Bielicki, A. Mertens, R. Quarck, N. Benhabiles, G. Marguerie, et al.
Weight Loss-Associated Induction of Peroxisome Proliferator-Activated Receptor-{alpha} and Peroxisome Proliferator-Activated Receptor-{gamma} Correlate With Reduced Atherosclerosis and Improved Cardiovascular Function in Obese Insulin-Resistant Mice
Circulation, November 16, 2004; 110(20): 3259 - 3269.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Favari, M. Lee, L. Calabresi, G. Franceschini, F. Zimetti, F. Bernini, and P. T. Kovanen
Depletion of Pre-{beta}-high Density Lipoprotein by Human Chymase Impairs ATP-binding Cassette Transporter A1- but Not Scavenger Receptor Class B Type I-mediated Lipid Efflux to High Density Lipoprotein
J. Biol. Chem., March 12, 2004; 279(11): 9930 - 9936.
[Abstract] [Full Text] [PDF]


ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2002 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.