J. Lipid Res. Did you know there is a large type edition? Click here.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on September 1, 2004

Papers In Press, published online ahead of print July 1, 2004
J. Lipid Res., doi:10.1194/jlr.M400176-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M400176-JLR200v1
45/9/1633    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Turunen, P.
Right arrow Articles by Ylä-Herttuala, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Turunen, P.
Right arrow Articles by Ylä-Herttuala, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Submitted on May 6, 2004
Revised on June 23, 2004
Accepted on June 29, 2004

Adenovirus-mediated gene transfer of Lp-PLA2 reduces LDL degradation and foam-cell formation in vitro

Päivi Turunen, Johanna Jalkanen, Tommi Heikura, Hanna L. Puhakka, Jouni Karppi, Kristiina Nyyssönen, and Seppo Ylä-Herttuala

University of Kuopio, Kuopio 70211

Corresponding Author: Paivi.Turunen{at}uku.fi

Objective: Oxidative modification of low-density lipoprotein (LDL) generates biologically active platelet activating factor (PAF)-like phospholipid derivatives with polar fatty acid chains, which have potent proinflammatory activity. These products are inactivated by lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme capable of hydrolysing PAF and PAF-like phospholipids. In this study we have generated an adenovirus (Ad) encoding human Lp-PLA2 and injected 108, 109 and 1010 pfu doses of the AdLp-PLA2 and control AdLacZ intra-arterially into New Zealand White rabbits in order to achieve overexpression of Lp-PLA2 in liver and in vivo production of Lp-PLA2-enriched LDL particles. Methods and Results: As a result, LDL particles with 3-fold increased Lp-PLA2 activity were produced with the highest dose of AdLp-PLA2. LDL from these animals were oxidized and tested for degradation activity and foam-cell formation in RAW 264 murine macrophages. Increased Lp-PLA2 activity in LDL particles decreased degradation rate to 60-80% as compared to LDL isolated from LacZ transfected control rabbits. The decrease was proportional to the virus dose and Lp-PLA2 activity. Lipid accumulation and foam-cell formation in RAW 264 macrophages was decreased when incubated with oxidized LDL containing the highest Lp- PLA2 activity. Inhibition of the Lp-PLA2 activity in the LDL particles led to an increase in lipid accumulation and foam-cell formation. No inflammatory responses were detected inmacrophages after AdLp-PLA2 transduction. Conclusion: It is concluded that increased Lp- PLA2 activity in LDL attenuates foam cell formation and decreases LDL degradation in macrophages.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 CirculationHome page
A.-L. Levonen, E. Vahakangas, J. K. Koponen, and S. Yla-Herttuala
Antioxidant Gene Therapy for Cardiovascular Disease: Current Status and Future Perspectives
Circulation, April 22, 2008; 117(16): 2142 - 2150.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Kodvawala, A. B. Ghering, W. S. Davidson, and D. Y. Hui
Carboxyl Ester Lipase Expression in Macrophages Increases Cholesteryl Ester Accumulation and Promotes Atherosclerosis
J. Biol. Chem., November 18, 2005; 280(46): 38592 - 38598.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.