Document Detail


Lysosomal acid lipase and atherosclerosis.
MedLine Citation:
PMID:  15361789     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Atherosclerosis remains the leading cause of death in the developed countries. In addition to lipid-lowering drugs - statins, dietary control, and exercise, new approaches are needed for the treatment and prevention of atherosclerosis. This review will focus on the role(s) of lysosomal acid lipase and its use as an enzyme therapy to reduce atherosclerotic lesions in a mouse model and to examine the molecular basis supporting this novel strategy and its mechanism of effect. RECENT FINDINGS: Administration of human lysosomal acid lipase via tail vein into mice with atherosclerosis eliminates early aortic and coronary ostial lesions and reduces lesional size in advanced disease. The reduction of advanced lesional area is related to decreases in foamy macrophages, collagen positive areas, and necrotic areas. Compared with sham-treated mice, the human lysosomal acid lipase-treated mice also have reduced levels of plasma cholesteryl esters, and reduced levels of hepatic cholesterol and triglycerides. SUMMARY: These studies indicate that administrated lysosomal acid lipase affects the atherogenesis by at least two mechanisms: (1) direct targeting of lesional macrophages with resultant decreases in cholesteryl esters and triglyceride in the lysosomes of macrophages in the lesions; (2) systemic effects that mediate the liver to reduce the hepatic cholesteryl ester and triglyceride release, possibly leading to reduced production of VLDL and LDL.
Authors:
Hong Du; Gregory A Grabowski
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current opinion in lipidology     Volume:  15     ISSN:  0957-9672     ISO Abbreviation:  Curr. Opin. Lipidol.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-13     Completed Date:  2005-03-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  England    
Other Details:
Languages:  eng     Pagination:  539-44     Citation Subset:  IM    
Affiliation:
The Children's Hospital Research Foundation of Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229-3039, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arteriosclerosis / enzymology,  pathology*
Cholesterol Esters
Clinical Trials as Topic
Cytoplasm / metabolism
DNA, Complementary / metabolism
Humans
Lipase / physiology*
Lysosomes / enzymology*,  metabolism
Macrophages
Models, Biological
Triglycerides / metabolism
Chemical
Reg. No./Substance:
0/Cholesterol Esters; 0/DNA, Complementary; 0/Triglycerides; EC 3.1.1.3/Lipase

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


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