Published online before print March 4, 2004, doi: 10.1161/01.RES.0000124920.09738.26
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 5, 2003
Revised on February 19, 2004
Accepted on February 20, 2004
Glucose Enhances Human Macrophage LOX-1 Expression. Role for LOX-1 in Glucose-Induced Macrophage Foam Cell Formation
Ling Li ;
From the Department of Biomedical Sciences (L.L.) and Medicine (G.R.), University of Montreal, Centre Hospitalier de l’Université de Montréal (CHUM) Research Centre, Notre-Dame Hospital, Montreal, Quebec, Canada, and the Department of Bioscience (T.S.), National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka, Japan.
* To whom correspondence should be addressed. E-mail: genevieve.renier{at}umontreal.ca.
Lectin-like oxidized LDL receptor-1 (LOX-1) is a newly identified receptor for oxidized LDL that is expressed by vascular cells. LOX-1 is upregulated in aortas of diabetic rats and thus may contribute to the pathogenesis of human diabetic atherosclerosis. In this study, we examined the regulation of human monocyte-derived macrophage (MDM) LOX-1 expression by high glucose and the role of LOX-1 in glucose-induced foam cell formation. Incubation of human MDMs with glucose (5.6 to 30 mmol/L) enhanced, in a dose- and time-dependent manner, LOX-1 gene and protein expression. Induction of LOX-1 gene expression by high glucose was abolished by antioxidants, protein kinase C (PKC), mitogen-activated protein kinases, nuclear factor-
B, and AP-1 inhibitors. In human MDMs cultured with high glucose, increased expression of PKC
2 and enhanced phosphorylation of extracellular signal-regulated protein kinase 1/2 was observed. Activation of these kinases was inhibited by the antioxidant N-acetyl-L-cysteine and by the PKC inhibitor LY379196. High glucose also enhanced the binding of nuclear proteins extracted from human MDMs to the nuclear factor-B and AP-1 regulatory elements of the LOX-1 gene promoter. This effect was abrogated by NAC and PKC/mitogen-activated protein kinase inhibitors. Finally, high glucose induced human macrophage-derived foam cell formation through a LOX-1-dependent pathway. Overall, these results demonstrate that high glucose concentrations enhance LOX-1 expression in human MDMs and that this effect is associated with foam cell formation. Pilot data showing that MDMs of patients with type 2 diabetes overexpress LOX-1 support the relevance of this work to human diabetic atherosclerosis.
Key words: macrophages • lectin-like oxidized low-density lipoprotein receptor-1 • glucose • diabetes • foam cell formation
This article has been cited by other articles:
 |
|
 |
|
  A. M. Vincent, J. M. Hayes, L. L. McLean, A. Vivekanandan-Giri, S. Pennathur, and E. L. Feldman Dyslipidemia-Induced Neuropathy in Mice: The Role of oxLDL/LOX-1 Diabetes, October 1, 2009; 58(10): 2376 - 2385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Osto, A. Kouroedov, P. Mocharla, A. Akhmedov, C. Besler, L. Rohrer, A. von Eckardstein, S. Iliceto, M. Volpe, T. F. Luscher, et al. Inhibition of Protein Kinase C{beta} Prevents Foam Cell Formation by Reducing Scavenger Receptor A Expression in Human Macrophages Circulation, November 18, 2008; 118(21): 2174 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Ethier-Chiasson, J-C Forest, Y Giguere, A Masse, C Marseille-Tremblay, E Levy, and J Lafond Modulation of placental protein expression of OLR1: implication in pregnancy-related disorders or pathologies Reproduction, October 1, 2008; 136(4): 491 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. B. Tan, S. W. M. Shiu, Y. Wong, L. Leng, and R. Bucala Soluble lectin-like oxidized low density lipoprotein receptor-1 in type 2 diabetes mellitus J. Lipid Res., July 1, 2008; 49(7): 1438 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Mauldin, M. H. Nagelin, A. J. Wojcik, S. Srinivasan, M. D. Skaflen, C. R. Ayers, C. A. McNamara, and C. C. Hedrick Reduced Expression of ATP-Binding Cassette Transporter G1 Increases Cholesterol Accumulation in Macrophages of Patients With Type 2 Diabetes Mellitus Circulation, May 27, 2008; 117(21): 2785 - 2792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Singh, M. R. Dasu, P. G. Yancey, A. Afify, S. Devaraj, and I. Jialal Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats J. Lipid Res., May 1, 2008; 49(5): 1015 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. S. Yang, J. W. Seo, N. J. Han, J. Choi, K.-U. Lee, H. Ahn, S. K. Lee, and S.-K. Park High glucose-induced NF-{kappa}B activation occurs via tyrosine phosphorylation of I{kappa}B{alpha} in human glomerular endothelial cells: involvement of Syk tyrosine kinase Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1065 - F1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Dominguez, J. L. Mehta, D. Li, P. Wu, K. J. Kelly, C. S. Packer, C. Temm, E. Goss, L. Cheng, S. Zhang, et al. Anti-LOX-1 therapy in rats with diabetes and dyslipidemia: ablation of renal vascular and epithelial manifestations Am J Physiol Renal Physiol, January 1, 2008; 294(1): F110 - F119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Kanter, F. Johansson, R. C. LeBoeuf, and K. E. Bornfeldt Do Glucose and Lipids Exert Independent Effects on Atherosclerotic Lesion Initiation or Progression to Advanced Plaques? Circ. Res., March 30, 2007; 100(6): 769 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Thomas, G. B. Sala-Newby, Y. Ismail, J. L. Johnson, G. Pasterkamp, and A. C. Newby Genomics of Foam Cells and Nonfoamy Macrophages From Rabbits Identifies Arginase-I as a Differential Regulator of Nitric Oxide Production Arterioscler Thromb Vasc Biol, March 1, 2007; 27(3): 571 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Mauldin, S. Srinivasan, A. Mulya, A. Gebre, J. S. Parks, A. Daugherty, and C. C. Hedrick Reduction in ABCG1 in Type 2 Diabetic Mice Increases Macrophage Foam Cell Formation J. Biol. Chem., July 28, 2006; 281(30): 21216 - 21224. [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. E. Barbato, B. S. Zuckerbraun, M. Overhaus, K. G. Raman, and E. Tzeng Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H228 - H236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rask-Madsen and G. L. King Proatherosclerotic Mechanisms Involving Protein Kinase C in Diabetes and Insulin Resistance Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 487 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fukuhara-Takaki, M. Sakai, Y.-i. Sakamoto, M. Takeya, and S. Horiuchi Expression of Class A Scavenger Receptor Is Enhanced by High Glucose in Vitro and under Diabetic Conditions in Vivo: ONE MECHANISM FOR AN INCREASED RATE OF ATHEROSCLEROSIS IN DIABETES J. Biol. Chem., February 4, 2005; 280(5): 3355 - 3364. [Abstract] [Full Text] [PDF]
|
|