Mild hyperhomocysteinemia induced by feeding rats diets rich in methionine or deficient in folate promotes early atherosclerotic inflammatory processes.
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 kappaB 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 kappaB, 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.
Zhang
Ruifen
R
Department of Clinical Nutrition, Sun Yat-sen University, Guangzhou 510080, China.
Ma
Jing
J
Xia
Min
M
Zhu
Huilian
H
Ling
WengHua
W
D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D004032:Diet; D004730:Endothelium, Vascular / Q000378:metabolism; D005492:Folic Acid / Q000008:administration & dosage*; D005494:Folic Acid Deficiency / Q000150:complications; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000209:etiology; D007249:Inflammation / Q000209:etiology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008715:Methionine / Q000008:administration & dosage*; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D018932:Chemokine CCL2; D016328:NF-kappa B; D009573:Nitrites; D018799:Intercellular Adhesion Molecule-1; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D005492:Folic Acid; D008715:Methionine; D019001:Nitric Oxide Synthase