Document Detail

Lysosomal acid lipase and atherosclerosis.
MedLine Citation:
PMID:  15361789     Owner:  NLM     Status:  MEDLINE    
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.
Hong Du; Gregory A Grabowski
Related Documents :
2306509 - High-resolution electron density profiles reveal influence of fatty acids on bilayer st...
9299449 - Retinoids inhibit primary cynomolgus monkey hepatocyte lipoprotein(a) levels.
7142509 - Pulmonary edema: a ct study of regional changes in lung density following oleic acid in...
9219909 - Omega-3 fatty acid intake results in a relationship between the fatty acid composition ...
3179329 - Studies with etofibrate in the rat. part i: effects on glycerol, free fatty acid and tr...
9026539 - Oxidized lipids in the diet are incorporated by the liver into very low density lipopro...
1902219 - Biosynthesis of heparin. enzymatic sulfation of pentasaccharides.
1269619 - Uptake of l-glutamate and l-aspartate in neurones and glial cells of cultured human and...
19702659 - Glutamate metabolic pathways and retinal function.
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    
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.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Arteriosclerosis / enzymology,  pathology*
Cholesterol Esters
Clinical Trials as Topic
Cytoplasm / metabolism
DNA, Complementary / metabolism
Lipase / physiology*
Lysosomes / enzymology*,  metabolism
Models, Biological
Triglycerides / metabolism
Reg. No./Substance:
0/Cholesterol Esters; 0/DNA, Complementary; 0/Triglycerides; EC

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

Previous Document:  Acid sphingomyelinase in macrophage apoptosis.
Next Document:  Blocking endothelial adhesion molecules: a potential therapeutic strategy to combat atherogenesis.