© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation
Departments of Medicine and Physiology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System, Little Rock, AR, USA
* Corresponding author. Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, 4301 West Markham St., Mail Slot 532, Little Rock, AR 72205-7199, USA. Tel.: +1-501-296-1401; fax: +1-501-686-6180 mehtajl{at}uams.edu
Objectives: LOX-1, a lectin-like receptor on endothelial cells, facilitates the uptake of oxidized-LDL. Expression of LOX-1 is involved in the pathobiological effects of oxidized-LDL in endothelial cells, including apoptosis, suppression of cNOS activity and cell adhesion. Recent studies show that intracellular signal protein kinase B (PKB) is involved in the regulation of cNOS. Further, HMG CoA reductase inhibitors (statins) may affect LOX-1 expression. In this study, we examined the modulation of LOX-1 expression and PKB activity in response to oxidized-LDL by two different statins (simvastatin and atorvastatin). Methods and results: Cultured human coronary artery endothelial cells (HCAECs) were used in this study. Oxidized-LDL (40 µg/ml) was found to upregulate the expression of LOX-1 (mRNA and protein), enhance [125I]-ox-LDL uptake and to reduce the phosphorylation of PKB (p-PKB). Two different statins, simvastatin and atorvastatin (each 1 and 10 µM), upregulated the activity of PKB and decreased LOX-1 expression and [125I]-ox-LDL uptake. A high concentration of statins (10 µM) gave a more potent effect than the low concentration (1 µM). The effects of the two different statins were similar. Conclusions: These observations show that statins decrease LOX-1 expression, a novel oxidized-LDL endothelial receptor, and uptake of oxidized-LDL in HCAECs. The effect of statins on LOX-1 expression is associated with an increase in PKB activity in HCAECs.
KEYWORDS Endothelial function; Lipoproteins; Protein kinases; Statins
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B.-Y. Kang and J. L. Mehta Rosuvastatin Attenuates Ang II--Mediated Cardiomyocyte Hypertrophy via Inhibition of LOX-1 Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2009; 14(4): 283 - 291. [Abstract] [PDF]
|
|
|
|
 |
|
 L. Zhang, Y. Liu, X. T. Lu, Y. L. Wu, C. Zhang, X. P. Ji, R. Wang, C. X. Liu, J. B. Feng, H. Jiang, et al. Traditional Chinese medication Tongxinluo dose-dependently enhances stability of vulnerable plaques: a comparison with a high-dose simvastatin therapy Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2004 - H2014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. X. Ma, B. Zhou, Z. Chen, Q. Ren, S. H. Lu, T. Sawamura, and Z. C. Han Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase J. Lipid Res., June 1, 2006; 47(6): 1227 - 1237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Hofnagel, B. Luechtenborg, H. Eschert, G. Weissen-Plenz, N. J. Severs, and H. Robenek Pravastatin Inhibits Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 (LOX-1) in Watanabe Heritable Hyperlipidemic Rabbits: A New Pleiotropic Effect of Statins Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 604 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Mehta, J. Chen, P. L. Hermonat, F. Romeo, and G. Novelli Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): A critical player in the development of atherosclerosis and related disorders Cardiovasc Res, January 1, 2006; 69(1): 36 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.L. Mehta, J. Chen, F. Yu, and D.Y. Li Aspirin inhibits ox-LDL-mediated LOX-1 expression and metalloproteinase-1 in human coronary endothelial cells Cardiovasc Res, November 1, 2004; 64(2): 243 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Davignon Beneficial Cardiovascular Pleiotropic Effects of Statins Circulation, June 15, 2004; 109(23_suppl_1): III-39 - III-43. [Abstract] [Full Text]
|
|
|
|
|
|
Z. S. Katusic, N. M. Caplice, and K. A. Nath Nitric Oxide Synthase Gene Transfer as a Tool to Study Biology of Endothelial Cells Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 1990 - 1994. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-W. Chien, C.-S. Chien, L.-D. Hsiao, C.-H. Lin, and C.-M. Yang OxLDL induces mitogen-activated protein kinase activation mediated via PI3-kinase/Akt in vascular smooth muscle cells J. Lipid Res., September 1, 2003; 44(9): 1667 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, L. Liu, H. Chen, T. Sawamura, and J. L. Mehta LOX-1, an Oxidized LDL Endothelial Receptor, Induces CD40/CD40L Signaling in Human Coronary Artery Endothelial Cells Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 816 - 821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. Sack and D. M. Yellon Insulin therapy as an adjunct toreperfusion after acute coronary ischemia: A proposed direct myocardial cell survival effect independent of metabolic modulation J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1404 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, L. Liu, H. Chen, T. Sawamura, S. Ranganathan, and J. L. Mehta LOX-1 Mediates Oxidized Low-Density Lipoprotein-Induced Expression of Matrix Metalloproteinases in Human Coronary Artery Endothelial Cells Circulation, February 4, 2003; 107(4): 612 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, R. M. Singh, L. Liu, H. Chen, B. M. Singh, N. Kazzaz, and J. L. Mehta Oxidized-LDL through LOX-1 increases the expression of angiotensin converting enzyme in human coronary artery endothelial cells Cardiovasc Res, January 1, 2003; 57(1): 238 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, H. Chen, F. Romeo, T. Sawamura, T. Saldeen, and J. L. Mehta Statins Modulate Oxidized Low-Density Lipoprotein-Mediated Adhesion Molecule Expression in Human Coronary Artery Endothelial Cells: Role of LOX-1 J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 601 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Scotland, M. Morales-Ruiz, Y. Chen, J. Yu, R. D. Rudic, D. Fulton, J.-P. Gratton, and W. C. Sessa Functional Reconstitution of Endothelial Nitric Oxide Synthase Reveals the Importance of Serine 1179 in Endothelium-Dependent Vasomotion Circ. Res., May 3, 2002; 90(8): 904 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J Miller Emerging mechanisms for secondary cardioprotective effects of statins Cardiovasc Res, October 1, 2001; 52(1): 5 - 7. [Full Text] [PDF]
|
|
|
|
|
|
R. S. Scotland, M. Morales-Ruiz, Y. Chen, J. Yu, R. D. Rudic, D. Fulton, J.-P. Gratton, and W. C. Sessa Functional Reconstitution of Endothelial Nitric Oxide Synthase Reveals the Importance of Serine 1179 in Endothelium-Dependent Vasomotion Circ. Res., May 3, 2002; 90(8): 904 - 910. [Abstract] [Full Text] [PDF]
|
|