Published online before print August 29, 2002, doi: 10.1161/01.ATV.0000035404.18281.37
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Vascular Biology |
Increased Monocyte Adhesion to Aortic Endothelium in Rats With Hyperhomocysteinemia
Role of Chemokine and Adhesion Molecules
From the Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong, China.
Correspondence to Dr Karmin O, MB, PhD, Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, 2/F, Laboratory Block, New Medical Complex, 21 Sassoon Rd, Hong Kong, China. E-mail okarmin{at}hkucc.hku.hk
Objective— The stimulatory effect of homocysteine (Hcy) on monocyte chemoattractant protein (MCP)-1 expression in vitro has been suggested to play an important role in Hcy-mediated atherosclerosis. We investigated whether such a stimulatory effect occurs in vivo, leading to monocyte adhesion to the endothelium.
Methods and Results— Sprague-Dawley rats were divided into 4 groups. Hyperhomocysteinemia was induced in 1 group of rats after 4 weeks of a high-methionine diet (serum Hcy levels were 4- to 5-fold higher than levels in control rats). The number of ED-1–positive cells present on the surface of aortic endothelium was significantly elevated in hyperhomocysteinemic rats. There was a significant increase in the expression of MCP-1, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in the endothelium. Antibodies recognizing MCP-1, VCAM-1, or E-selectin could abolish the enhanced monocyte binding to the aortic endothelium of hyperhomocysteinemic rats. Endothelium-dependent aortic relaxation was impaired in hyperhomocysteinemic rats.
Conclusions— These results suggest that in the absence of other known risk factors, hyperhomocysteinemia stimulates the expression of MCP-1, VCAM-1, and E-selectin in vivo, leading to increased monocyte adhesion to the aortic endothelium. Such an effect may contribute significantly to the development of atherosclerosis by facilitating monocyte/macrophage infiltration into the arterial wall.
Key Words: hyperhomocysteinemia • atherosclerosis • monocyte chemoattractant protein-1 • cytokines • monocytes
This article has been cited by other articles:
 |
|
 |
|
  N. Wu, Y. L. Siow, and K. O Induction of hepatic cyclooxygenase-2 by hyperhomocysteinemia via nuclear factor-{kappa}B activation Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R1086 - R1094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jakubowski, J. Perla-Kajan, R. H. Finnell, R. M. Cabrera, H. Wang, S. Gupta, W. D. Kruger, J. P. Kraus, and D. M. Shih Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in mice FASEB J, June 1, 2009; 23(6): 1721 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Y. Chang, S.-C. Lu, C.-M. Lee, Y.-J. Chen, T. A. Dugan, W.-H. Huang, S.-F. Chang, W. S.L. Liao, C.-H. Chen, and Y.-T. Lee Homocysteine Inhibits Arterial Endothelial Cell Growth Through Transcriptional Downregulation of Fibroblast Growth Factor-2 Involving G Protein and DNA Methylation Circ. Res., April 25, 2008; 102(8): 933 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Li, C. Jiang, G. Xu, N. Wang, Y. Zhu, C. Tang, and X. Wang Homocysteine Upregulates Resistin Production From Adipocytes In Vivo and In Vitro Diabetes, April 1, 2008; 57(4): 817 - 827. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. H. Woo, Y. L. Siow, and K. O Homocysteine Induces Monocyte Chemoattractant Protein-1 Expression in Hepatocytes Mediated via Activator Protein-1 Activation J. Biol. Chem., January 18, 2008; 283(3): 1282 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-Y. Hwang, C. W. H. Woo, K. K. W. Au-Yeung, Y. L. Siow, T. Y. Zhu, and K. O Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-{kappa}B activation Am J Physiol Renal Physiol, January 1, 2008; 294(1): F236 - F244. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Carluccio, M. A. Ancora, M. Massaro, M. Carluccio, E. Scoditti, A. Distante, C. Storelli, and R. De Caterina Homocysteine induces VCAM-1 gene expression through NF-{kappa}B and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2344 - H2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. A. Prathapasinghe, Y. L. Siow, and K. O Detrimental role of homocysteine in renal ischemia-reperfusion injury Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1354 - F1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Ting, J. P. Stice, U. Y. Schaff, D. Y. Hui, J. C. Rutledge, A. A. Knowlton, A. G. Passerini, and S. I. Simon Triglyceride-Rich Lipoproteins Prime Aortic Endothelium for an Enhanced Inflammatory Response to Tumor Necrosis Factor-{alpha} Circ. Res., February 16, 2007; 100(3): 381 - 390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Antoniades, D. Tousoulis, K. Marinou, C. Vasiliadou, C. Tentolouris, G. Bouras, C. Pitsavos, and C. Stefanadis Asymmetrical dimethylarginine regulates endothelial function in methionine-induced but not in chronic homocystinemia in humans: effect of oxidative stress and proinflammatory cytokines. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 781 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W.H. Woo, Y. L. Siow, and K. O Homocysteine Activates cAMP-response Element Binding Protein in HepG2 Through cAMP/PKA Signaling Pathway Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1043 - 1050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Postea, F. Krotz, A. Henger, C. Keller, and N. Weiss Stereospecific and Redox-Sensitive Increase in Monocyte Adhesion to Endothelial Cells by Homocysteine Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 508 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Kamath, A. K. Chauhan, J. Kisucka, V. S. Dole, J. Loscalzo, D. E. Handy, and D. D. Wagner Elevated levels of homocysteine compromise blood-brain barrier integrity in mice Blood, January 15, 2006; 107(2): 591 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Jiang, F. Yang, H. Tan, D. Liao, R. M. Bryan Jr, J. K. Randhawa, R. E. Rumbaut, W. Durante, A. I. Schafer, X. Yang, et al. Hyperhomocystinemia Impairs Endothelial Function and eNOS Activity via PKC Activation Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2515 - 2521. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Durga, L. J. H. van Tits, E. G. Schouten, F. J. Kok, and P. Verhoef Effect of Lowering of Homocysteine Levels on Inflammatory Markers: A Randomized Controlled Trial Arch Intern Med, June 27, 2005; 165(12): 1388 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kojma, K.-i. Hirata, T. Ishida, Y. Shimokawa, N. Inoue, S. Kawashima, T. Quertermous, and M. Yokoyama Endothelial Lipase Modulates Monocyte Adhesion to the Vessel Wall: A POTENTIAL ROLE IN INFLAMMATION J. Biol. Chem., December 24, 2004; 279(52): 54032 - 54038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, G. K. Sukhova, J.-S. Sun, W.-H. Xu, P. Libby, and G.-P. Shi Lysosomal Cysteine Proteases in Atherosclerosis Arterioscler Thromb Vasc Biol, August 1, 2004; 24(8): 1359 - 1366. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhou, G. H. Werstuck, S. Lhotak, A. B. L. de Koning, S. K. Sood, G. S. Hossain, J. Moller, M. Ritskes-Hoitinga, E. Falk, S. Dayal, et al. Association of Multiple Cellular Stress Pathways With Accelerated Atherosclerosis in Hyperhomocysteinemic Apolipoprotein E-Deficient Mice Circulation, July 13, 2004; 110(2): 207 - 213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Suhara, K. Fukuo, O. Yasuda, M. Tsubakimoto, Y. Takemura, H. Kawamoto, T. Yokoi, M. Mogi, T. Kaimoto, and T. Ogihara Homocysteine Enhances Endothelial Apoptosis via Upregulation of Fas-Mediated Pathways Hypertension, June 1, 2004; 43(6): 1208 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhang, J. Ma, M. Xia, H. Zhu, and W. Ling Mild Hyperhomocysteinemia Induced by Feeding Rats Diets Rich in Methionine or Deficient in Folate Promotes Early Atherosclerotic Inflammatory Processes J. Nutr., April 1, 2004; 134(4): 825 - 830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K.W. Au-Yeung, C. W.H. Woo, F. L. Sung, J. C.W. Yip, Y. L. Siow, and K. O Hyperhomocysteinemia Activates Nuclear Factor-{kappa}B in Endothelial Cells via Oxidative Stress Circ. Res., January 9, 2004; 94(1): 28 - 36. [Abstract] [Full Text] [PDF]
|
|