QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, R. Articles by Ling, W. Search for Related Content PubMed PubMed Citation Articles by Zhang, R. Articles by Ling, W.

---

Nutrient Metabolism

Mild Hyperhomocysteinemia Induced by Feeding Rats Diets Rich in Methionine or Deficient in Folate Promotes Early Atherosclerotic Inflammatory Processes¹

Department of Clinical Nutrition, Sun Yat-sen University, Guangzhou 510080, China

²To whom correspondence should be addressed. E-mail: whling{at}gzsums.edu.cn.

High homocysteine levels in vitro promote the expression of inflammatory agents responsible for atherogenesis. We investigated the long-term effects of elevated plasma homocysteine on the expression of inflammatory molecules and attempted to elucidate their mechanisms. Male Sprague-Dawley rats (n = 36) were randomly divided into 3 groups, which received the control AIN-93G diet, the control diet plus 10 g/kg of L-methionine, or that diet without folate (0 m/kg) for 14 wk. Mild hyperhomocysteinemia was then induced in both experimental groups. The mildly hyperhomocysteinemic rats had markedly increased expression of intracellular adhesion molecule-1 (ICAM-1) in the aorta and elevated serum levels of monocyte chemoattractant protein-1 (MCP-1), compared to the control rats. The activation of nuclear factor B and formation of nitrotyrosine in the aorta were greater in rats with mild hyperhomocysteinemia than in control rats. Serum levels of malonyldialdehyde (MDA) were higher in mildly hyperhomocysteinemic rats than in control rats. These results suggest that the oxidative stress resulting from elevated plasma homocysteine stimulates the activation of nuclear factor B, and consequently increases the expression of the inflammatory factors in vivo. Such an effect may contribute to atherogenesis by enhancing the inflammatory response of the vascular endothelium.

KEY WORDS: • atherosclerosis • homocysteine • inflammatory factors • nuclear factor B • oxidative stress

This article has been cited by other articles:

				C. Liu, Q. Wang, H. Guo, M. Xia, Q. Yuan, Y. Hu, H. Zhu, M. Hou, J. Ma, Z. Tang, et al. Plasma S-Adenosylhomocysteine Is a Better Biomarker of Atherosclerosis Than Homocysteine in Apolipoprotein E-Deficient Mice Fed High Dietary Methionine J. Nutr., February 1, 2008; 138(2): 311 - 315. [Abstract] [Full Text] [PDF]

				P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]

				J. T. Dever and A. A. Elfarra In Vivo Metabolism of L-Methionine in Mice: Evidence for Stereoselective Formation of Methionine-d-Sulfoxide and Quantitation of Other Major Metabolites Drug Metab. Dispos., December 1, 2006; 34(12): 2036 - 2043. [Abstract] [Full Text] [PDF]

				S. Toue, R. Kodama, M. Amao, Y. Kawamata, T. Kimura, and R. Sakai Screening of Toxicity Biomarkers for Methionine Excess in Rats J. Nutr., June 1, 2006; 136(6): 1716S - 1721S. [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]

				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]