(Circulation. 2000;101:2889.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Antisense to LOX-1 Inhibits Oxidized LDL–Mediated Upregulation of Monocyte Chemoattractant Protein-1 and Monocyte Adhesion to Human Coronary Artery Endothelial Cells
From the Departments of Medicine and Physiology, University of Florida and VA Medical Center, Gainesville, Fla.
Correspondence to J.L. Mehta, MD, PhD, Department of Medicine, University of Florida College of Medicine, 1600 Archer Rd, PO Box 100277 JHMHC, Gainesville, FL 32610. E-mail mehta{at}medmac.ufl.edu
Background—We have recently demonstrated a lectin-like receptor for oxidized (ox)-LDL (LOX-1) in human coronary artery endothelial cells (HCAECs). This receptor is upregulated by ox-LDL. The present study examined the significance of LOX-1 in monocyte adhesion to HCAECs and endothelial injury in response to ox-LDL.
Methods and Results—HCAECs were incubated in the presence of antisense oligodeoxynucleotides to the 5'-coding sequence of the human LOX-1 gene (0.5 µm/L). Basal LOX-1 mRNA and protein were suppressed by antisense LOX-1. Ox-LDL–mediated upregulation of LOX-1 was also suppressed by antisense LOX-1. Incubation of HCAECs with ox-LDL (40 µg/mL) for 24 hours markedly increased monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression as well as monocyte adhesion to HCAECs (P<0.01). After 48 hours of preincubation of HCAECs with antisense LOX-1, ox-LDL–mediated upregulation of MCP-1 and monocyte adhesion to HCAECs both were suppressed (P<0.01), whereas sense LOX-1 had no effect. Whereas antisense or sense LOX-1 alone (both 0.5 nmol/L) did not injure the cells, antisense LOX-1, but not sense LOX-1, reduced ox-LDL–mediated HCAEC injury, determined as LDH release (P<0.01). Activation of mitogen-activated protein kinase (MAPK) may play a critical role in signal transduction in ox-LDL–mediated alteration in MCP-1 expression, since antisense LOX-1, but not the sense LOX-1, completely inhibited the ox-LDL–induced MAPK activation.
Conclusions—These observations with the first use of a specific antisense to human LOX-1 mRNA suggest that LOX-1 is a key factor in ox-LDL–mediated monocyte adhesion to HCAECs.
Key Words: endothelium • receptors • lipoproteins • cell adhesion molecules • gene therapy
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 E.-H. Yao, N. Fukuda, T. Ueno, H. Matsuda, K. Matsumoto, H. Nagase, Y. Matsumoto, A. Takasaka, K. Serie, H. Sugiyama, et al. Novel Gene Silencer Pyrrole-Imidazole Polyamide Targeting Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Attenuates Restenosis of the Artery After Injury Hypertension, July 1, 2008; 52(1): 86 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mollace, S. Ragusa, I. Sacco, C. Muscoli, F. Sculco, V. Visalli, E. Palma, S. Muscoli, L. Mondello, P. Dugo, et al. The Protective Effect of Bergamot Oil Extract on Lecitine-like OxyLDL Receptor-1 Expression in Balloon Injury-related Neointima Formation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 120 - 129. [Abstract] [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]
|
|
|
|
 |
|
 A. Dandapat, C. Hu, L. Sun, and J. L. Mehta Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1 Dependent Redox-Sensitive Pathway Arterioscler. Thromb. Vasc. Biol., November 1, 2007; 27(11): 2435 - 2442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Maki-Petaja, A. D. Booth, F. C. Hall, S. M.L. Wallace, J. Brown, C. M. McEniery, and I. B. Wilkinson Ezetimibe and Simvastatin Reduce Inflammation, Disease Activity, and Aortic Stiffness and Improve Endothelial Function in Rheumatoid Arthritis J. Am. Coll. Cardiol., August 28, 2007; 50(9): 852 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Y. Zheng and L. Liu Remnant-like lipoprotein particles impair endothelial function: direct and indirect effects on nitric oxide synthase J. Lipid Res., August 1, 2007; 48(8): 1673 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Gleissner, N. Leitinger, and K. Ley Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis Hypertension, August 1, 2007; 50(2): 276 - 283. [Full Text] [PDF]
|
|
|
|
|
|
E. O. Apostolov, S. V. Shah, E. Ok, and A. G. Basnakian Carbamylated Low-Density Lipoprotein Induces Monocyte Adhesion to Endothelial Cells Through Intercellular Adhesion Molecule-1 and Vascular Cell Adhesion Molecule-1 Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 826 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ikonen Mechanisms for cellular cholesterol transport: defects and human disease. Physiol Rev, October 1, 2006; 86(4): 1237 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tanigawa, S.-i. Miura, Y. Matsuo, M. Fujino, T. Sawamura, and K. Saku Dominant-Negative Lox-1 Blocks Homodimerization of Wild-Type Lox-1-Induced Cell Proliferation Through Extracellular Signal Regulated Kinase 1/2 Activation Hypertension, August 1, 2006; 48(2): 294 - 300. [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]
|
|
|
|
|
|
D. Li and J. L. Mehta Oxidized LDL, a critical factor in atherogenesis Cardiovasc Res, December 1, 2005; 68(3): 353 - 354. [Full Text] [PDF]
|
|
|
|
|
|
S. Takai, D. Jin, M. Muramatsu, K. Kirimura, H. Sakonjo, and M. Miyazaki Eplerenone Inhibits Atherosclerosis in Nonhuman Primates Hypertension, November 1, 2005; 46(5): 1135 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chen, J. Chen, Y. Liu, J. Xie, D. Li, T. Sawamura, P. L. Hermonat, and J. L. Mehta Adhesion Molecule Expression in Fibroblasts: Alteration in Fibroblast Biology After Transfection With LOX-1 Plasmids Hypertension, September 1, 2005; 46(3): 622 - 627. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Inoue, Y. Arai, H. Kurihara, T. Kita, and T. Sawamura Overexpression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Induces Intramyocardial Vasculopathy in Apolipoprotein E-Null Mice Circ. Res., July 22, 2005; 97(2): 176 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum and J. Bauersachs Spotlight on endothelial progenitor cell inhibitors: short review Vascular Medicine, May 1, 2005; 10(2_suppl): S59 - S64. [Abstract] [PDF]
|
|
|
|
 |
|
 H. Park, F. G. Adsit, and J. C. Boyington The 1.4 A Crystal Structure of the Human Oxidized Low Density Lipoprotein Receptor Lox-1 J. Biol. Chem., April 8, 2005; 280(14): 13593 - 13599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Chen, J. L. Mehta, D. Li, L. Joseph, and J. Joseph Transforming Growth Factor {beta} Receptor Endoglin Is Expressed in Cardiac Fibroblasts and Modulates Profibrogenic Actions of Angiotensin II Circ. Res., December 10, 2004; 95(12): 1167 - 1173. [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]
|
|
|
|
|
|
L. Li, N. Roumeliotis, T. Sawamura, and G. Renier C-Reactive Protein Enhances LOX-1 Expression in Human Aortic Endothelial Cells: Relevance of LOX-1 to C-Reactive Protein-Induced Endothelial Dysfunction Circ. Res., October 29, 2004; 95(9): 877 - 883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Muscoli, I. Sacco, W. Alecce, E. Palma, R. Nistico, N. Costa, F. Clementi, D. Rotiroti, F. Romeo, D. Salvemini, et al. The Protective Effect of Superoxide Dismutase Mimetic M40401 on Balloon Injury-Related Neointima Formation: Role of the Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 44 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Shin, Y. K. Kim, K. Y. Kim, J. H. Lee, and K. W. Hong Remnant Lipoprotein Particles Induce Apoptosis in Endothelial Cells by NAD(P)H Oxidase-Mediated Production of Superoxide and Cytokines via Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Activation: Prevention by Cilostazol Circulation, March 2, 2004; 109(8): 1022 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kume and T. Kita Apoptosis of Vascular Cells by Oxidized LDL: Involvement of Caspases and LOX-1 and Its Implication in Atherosclerotic Plaque Rupture Circ. Res., February 20, 2004; 94(3): 269 - 270. [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, J. L. Mehta, N. Haider, X. Zhang, J. Narula, and D. Li Role of Caspases in Ox-LDL-Induced Apoptotic Cascade in Human Coronary Artery Endothelial Cells Circ. Res., February 20, 2004; 94(3): 370 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Thum and J. Borlak Mechanistic Role of Cytochrome P450 Monooxygenases in Oxidized Low-Density Lipoprotein-Induced Vascular Injury: Therapy Through LOX-1 Receptor Antagonism? Circ. Res., January 9, 2004; 94 (1): e1 - e13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Mango, F Clementi, P Borgiani, G B Forleo, M Federici, G Contino, E Giardina, L Garza, I E Fahdi, R Lauro, et al. Association of single nucleotide polymorphisms in the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction J. Med. Genet., December 1, 2003; 40(12): 933 - 936. [Full Text]
|
|
|
|
|
|
J. L. Mehta, B. Hu, J. Chen, and D. Li Pioglitazone Inhibits LOX-1 Expression in Human Coronary Artery Endothelial Cells by Reducing Intracellular Superoxide Radical Generation Arterioscler. Thromb. Vasc. Biol., December 1, 2003; 23(12): 2203 - 2208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Holven, H. Scholz, B. Halvorsen, P. Aukrust, L. Ose, and M. S. Nenseter Hyperhomocysteinemic Subjects Have Enhanced Expression of Lectin-Like Oxidized LDL Receptor-1 in Mononuclear Cells J. Nutr., November 1, 2003; 133(11): 3588 - 3591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Szmitko, C.-H. Wang, R. D. Weisel, G. A. Jeffries, T. J. Anderson, and S. Verma Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation: Part II Circulation, October 28, 2003; 108(17): 2041 - 2048. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Piemonti, G. Calori, A. Mercalli, G. Lattuada, P. Monti, M. P. Garancini, F. Costantino, G. Ruotolo, L. Luzi, and G. Perseghin Fasting Plasma Leptin, Tumor Necrosis Factor-{alpha} Receptor 2, and Monocyte Chemoattracting Protein 1 Concentration in a Population of Glucose-Tolerant and Glucose-Intolerant Women: Impact on cardiovascular mortality Diabetes Care, October 1, 2003; 26(10): 2883 - 2889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, T. Sawamura, and G. Renier Glucose Enhances Endothelial LOX-1 Expression: Role for LOX-1 in Glucose-Induced Human Monocyte Adhesion to Endothelium Diabetes, July 1, 2003; 52(7): 1843 - 1850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Singh and J. L. Mehta Interactions Between the Renin-Angiotensin System and Dyslipidemia: Relevance in the Therapy of Hypertension and Coronary Heart Disease Arch Intern Med, June 9, 2003; 163(11): 1296 - 1304. [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]
|
|
|
|
|
|
D. Li, V. Williams, L. Liu, H. Chen, T. Sawamura, F. Romeo, and J. L. Mehta Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1048 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cominacini, A. Fratta Pasini, U. Garbin, A. Pastorino, A. Rigoni, C. Nava, A. Davoli, V. Lo Cascio, and T. Sawamura The platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1 reduces the intracellular concentration of nitric oxide in endothelial cells J. Am. Coll. Cardiol., February 5, 2003; 41(3): 499 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Honjo, K. Nakamura, K. Yamashiro, J. Kiryu, H. Tanihara, L. M. McEvoy, Y. Honda, E. C. Butcher, T. Masaki, and T. Sawamura Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation PNAS, February 4, 2003; 100(3): 1274 - 1279. [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, V. Williams, L. Liu, H. Chen, T. Sawamura, T. Antakli, and J. L. Mehta LOX-1 inhibition in myocardial ischemia-reperfusion injury: modulation of MMP-1 and inflammation Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1795 - H1801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Y. Li, H. J. Chen, E. D. Staples, K. Ozaki, B. Annex, B. K. Singh, R. Vermani, and J. L. Mehtat Oxidized Low-Density Lipoprotein Receptor LOX-1 and Apoptosis in Human Atherosclerotic Lesions Journal of Cardiovascular Pharmacology and Therapeutics, September 1, 2002; 7(3): 147 - 153. [Abstract] [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]
|
|
|
|
|
|
J. L. Mehta and D. Li Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1429 - 1435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-B. Lei, Z. Zhang, Q. Jing, Y.-W. Qin, G. Pei, B.-Z. Cao, and X.-Y. Li OxLDL upregulates CXCR2 expression in monocytes via scavenger receptors and activation of p38 mitogen-activated protein kinase Cardiovasc Res, February 1, 2002; 53(2): 524 - 532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, H. Chen, and J. L. Mehta Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells Hypertension, November 1, 2001; 38(5): 1062 - 1067. [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]
|
|
|
|
|
|
D.Y Li, H.J Chen, and J.L Mehta Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation Cardiovasc Res, October 1, 2001; 52(1): 130 - 135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-Y. Chang, S. Luo, T. Jiang, Y.-T. Lee, S.-C. Lu, P. D. Henry, and C.-H. Chen Oxidized Low-Density Lipoprotein Downregulates Endothelial Basic Fibroblast Growth Factor Through a Pertussis Toxin-Sensitive G-Protein Pathway: Mediator Role of Platelet-Activating Factor-Like Phospholipids Circulation, July 31, 2001; 104(5): 588 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kataoka, N. Kume, S. Miyamoto, M. Minami, M. Morimoto, K. Hayashida, N. Hashimoto, and T. Kita Oxidized LDL Modulates Bax/Bcl-2 Through the Lectinlike Ox-LDL Receptor-1 in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 955 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Chen, D. Li, T. Saldeen, and J. L. Mehta Transforming Growth Factor-{beta}1 Modulates Oxidatively Modified LDL-Induced Expression of Adhesion Molecules: Role of LOX-1 Circ. Res., December 7, 2001; 89(12): 1155 - 1160. [Abstract] [Full Text] [PDF]
|
|