Document Detail


Phospholipase A(2)-modified LDL particles retain the generated hydrolytic products and are more atherogenic at acidic pH.
MedLine Citation:
PMID:  19473659     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Hydrolysis of LDL by phospholipase A(2) (PLA(2)) generates free fatty acids (FFAs) and lysophospholipids (lysoPCs). Binding of the PLA(2)-modified LDL to proteoglycans, and their uptake by macrophages are increased. Since the extracellular pH is locally decreased in advanced atherosclerotic plaques, we examined the effects of acidic pH on PLA(2)-induced LDL modification and its proatherogenic consequences. RESULTS: LDL particles were avidly hydrolyzed by sPLA(2)-V at pH range 7.5-5.5. With decreasing pH, the ability of albumin to sequester the formed FFAs and lysoPCs from the sPLA(2)-V-modified LDL particles decreased, and, as a consequence, more of the hydrolytic products accumulated in the particles. At acidic pH, the sPLA(2)-V-modified LDL particles had higher binding strength to human aortic proteoglycans, and their uptake by human monocyte-derived macrophages and ensuing foam cell formation were enhanced. CONCLUSIONS: The present data show that the proatherogenic effects exerted by sPLA(2)-V-induced lipolysis of LDL are enhanced with decreasing pH and suggest that sPLA(2)-V is particularly atherogenic in advanced atherosclerotic lesions, in which local acidic conditions prevail.
Authors:
Katariina L??hdesm??ki; Riia Plihtari; Pasi Soininen; Eva Hurt-Camejo; Mika Ala-Korpela; Katariina O??rni; Petri T Kovanen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-04
Journal Detail:
Title:  Atherosclerosis     Volume:  207     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-30     Completed Date:  2010-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  352-9     Citation Subset:  IM    
Affiliation:
Wihuri Research Institute, Kalliolinnantie 4, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Aorta / metabolism
Atherosclerosis / enzymology*
Cells, Cultured
Fatty Acids, Nonesterified / metabolism*
Foam Cells / enzymology*
Group V Phospholipases A2 / metabolism*
Humans
Hydrogen-Ion Concentration
Lipolysis*
Lipoproteins, LDL / metabolism*
Lysophospholipids / metabolism*
Protein Binding
Proteoglycans / metabolism
Recombinant Proteins / metabolism
Serum Albumin / metabolism
Time Factors
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Lipoproteins, LDL; 0/Lysophospholipids; 0/Proteoglycans; 0/Recombinant Proteins; 0/Serum Albumin; EC 3.1.1.4/Group V Phospholipases A2

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