Document Detail


Mast cell proteases: physiological tools to study functional significance of high density lipoproteins in the initiation of reverse cholesterol transport.
MedLine Citation:
PMID:  16530202     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The extracellular fluid of the intima is rich in lipid-poor species of high density lipoproteins (HDL) that promote efficient efflux of cholesterol from macrophages. Yet, during atherogenesis, cholesterol accumulates in macrophages, and foam cells are formed. We have studied proteolytic modification of HDL by mast cell proteases as a potential mechanism of reduced cholesterol efflux from foam cells. Mast cells are present in human atherosclerotic lesions and, when activated, they expel cytoplasmic granules that are filled with heparin proteoglycans and two neutral proteases, chymase and tryptase. Both proteases were found to specifically deplete in vitro the apoA-I-containing prebeta-migrating HDL (prebeta-HDL) and other lipid-poor HDL particles that contain only apoA-IV or apoE. These losses led to inhibition of the high-affinity component of cholesterol efflux from macrophage foam cells facilitated by the ATP-binding cassette transporter A1 (ABCA1). In contrast, the diffusional component of efflux promoted by alpha-HDL particles was not changed after proteolysis. Mast cell proteases are providing new insights into the role of extracellular proteolysis of HDL as an inhibiting principle of the initial steps of reverse cholesterol transport in the atherosclerotic intima, where many types of protease-secreting cells are present.
Authors:
M Lee-Rueckert; P T Kovanen
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2006-03-10
Journal Detail:
Title:  Atherosclerosis     Volume:  189     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-02     Completed Date:  2007-01-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  8-18     Citation Subset:  IM    
Affiliation:
Wihuri Research Institute, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Atherosclerosis / metabolism*,  pathology
Biological Transport / physiology
Extracellular Fluid / metabolism
Humans
Lipoproteins, HDL / metabolism*
Mast Cells / enzymology*
Peptide Hydrolases / metabolism*
Chemical
Reg. No./Substance:
0/Lipoproteins, HDL; EC 3.4.-/Peptide Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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