Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:175-180
Published online before print October 30, 2003, doi: 10.1161/01.ATV.0000104011.88939.06
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Data Supplement
Right arrow All Versions of this Article:
24/1/175    most recent
01.ATV.0000104011.88939.06v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rosenblat, M.
Right arrow Articles by Aviram, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rosenblat, M.
Right arrow Articles by Aviram, M.
Related Collections
Right arrow Lipids
Right arrow Cell biology/structural biology
Right arrow Gene expression
Right arrow Other arteriosclerosis
Right arrow Lipid and lipoprotein metabolism
Right arrow Mechanism of atherosclerosis/growth factors
(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:175.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Decreased Macrophage Paraoxonase 2 Expression in Patients With Hypercholesterolemia Is the Result of Their Increased Cellular Cholesterol Content: Effect of Atorvastatin Therapy

Mira Rosenblat; Tony Hayek; Khetam Hussein; Michael Aviram

From the Lipid Research Laboratory, Technion Faculty of Medicine (M.R., T.H., K.H., M.A.), The Rappaport Family Institute for Research in the Medical Sciences and Rambam Medical Center, and the Internal Medicine Department (H.T., H.K.), Rambam Medical Center, Haifa, Israel.

Correspondence to Prof. Michael Aviram, D.Sc, The Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel, 31096. E-mail aviram{at}tx.technion.ac.il

Objective— To analyze paraoxonase2 (PON2) expression in human monocyte-derived macrophages (HMDM) from patients with hypercholesterolemia in relation to cellular cholesterol and oxidative stress.

Methods and Results— Ten healthy subjects (controls) and 10 patients with hypercholesterolema who received 20-mg/d atorvastatin participated in the study. The patients’ versus controls’ HMDM demonstrated increased cholesterol content (270%) and oxidative stress (30% to 45%). Atorvastatin therapy reduced these parameters (59% and 25%, respectively). The patients’ versus controls’ macrophage-PON2 mRNA expression and PON2 activity were lower (100% and 40%, respectively), and atorvastatin therapy increased these parameters (76% and 200%, respectively). Untreated patient HMDM incubation with atorvastatin (0 to 10 µmol/L) resulted in a dose-dependent reduction in cellular cholesterol content and in cell-mediated low-density lipoprotein (LDL) oxidation up to 79% and 66%, respectively. In parallel, PON2 mRNA expression and PON2 activity increased dose-dependently up to 3.6- and 2.1-fold, respectively. On incubation of control HMDM with acetylated-LDL or aggregated-LDL, cellular cholesterol content increased (77% and 100%), and macrophage-PON2 activity decreased (49% and 22%), respectively. In contrast, oxidized LDL increased both cellular oxidative stress and PON2 expression.

Conclusions— HMDM-PON2 expression is reduced in patients with hypercholesterolemia as a result of their increased cellular cholesterol content. Atorvastatin therapy reduced both macrophage oxidative stress and cholesterol content, and upregulated PON2 expression, thus contributing to attenuation of foam cells formation.


Key Words: paraoxonase • oxidative stress • macrophages • cholesterol • atorvastatin




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
B. Fuhrman, A. Gantman, J. Khateeb, N. Volkova, S. Horke, J. Kiyan, I. Dumler, and M. Aviram
Urokinase activates macrophage PON2 gene transcription via the PI3K/ROS/MEK/SREBP-2 signalling cascade mediated by the PDGFR-{beta}
Cardiovasc Res, October 1, 2009; 84(1): 145 - 154.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
M. Rosenblat, R. Coleman, S. T. Reddy, and M. Aviram
Paraoxonase 2 attenuates macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1
J. Lipid Res., May 1, 2009; 50(5): 870 - 879.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
G. Fortunato, M. D. Di Taranto, U. M. Bracale, L. Del Guercio, F. Carbone, C. Mazzaccara, A. Morgante, F. P. D'Armiento, M. D'Armiento, M. Porcellini, et al.
Decreased Paraoxonase-2 Expression in Human Carotids During the Progression of Atherosclerosis
Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 594 - 600.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
C. S. Carlson, P. J. Heagerty, T. S. Hatsukami, R. J. Richter, J. Ranchalis, J. Lewis, T. J. Bacus, L. A. McKinstry, G. D. Schellenberg, M. Rieder, et al.
TagSNP analyses of the PON gene cluster: effects on PON1 activity, LDL oxidative susceptibility, and vascular disease
J. Lipid Res., May 1, 2006; 47(5): 1014 - 1024.
[Abstract] [Full Text] [PDF]


ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 2004 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.