This Article Full Text Full Text (PDF) All Versions of this Article: 22/4/699    most recent 01.ATV.0000013288.35930.90v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Holven, K. B. Articles by Nenseter, M. S. Search for Related Content PubMed PubMed Citation Articles by Holven, K. B. Articles by Nenseter, M. S. Related Collections Pathophysiology Risk Factors Other Vascular biology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:699.)
© 2002 American Heart Association, Inc.

Thrombosis

Folic Acid Treatment Reduces Chemokine Release From Peripheral Blood Mononuclear Cells in Hyperhomocysteinemic Subjects

Kirsten B. Holven; Pål Aukrust; Torbjørn Holm; Leiv Ose; Marit S. Nenseter

From the Lipid Clinic (K.B.H., L.O., M.S.N.), MSD Cardiovascular Research Center (K.B.H., M.S.N.), Research Institute for Internal Medicine (K.B.H., P.A., T.H., M.S.N.), Section of Clinical Immunology and Infection Diseases, Medical Department (P.A.), and Department of Cardiology, Division of Heart and Lung Diseases (T.H.), Rikshospitalet University Hospital, Oslo, Norway.

Correspondence to Dr Marit S. Nenseter, Research Institute for Internal Medicine, Rikshospitalet University Hospital, 0027 Oslo, Norway. E-mail maritn{at}klinmed.uio.no

Elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease. However, the mechanisms by which hyperhomocysteinemia induces vascular disease are uncertain. An early step in atherogenesis involves leukocyte migration into the arterial wall, a process regulated in part by chemokines. We hypothesized that homocysteine may exert its atherogenic effect in part through chemokine-mediated mechanisms, and in the present study, we examined the effects of folic acid supplementation for 6 weeks on chemokine levels in hyperhomocysteinemic individuals. Data showed the following: (1) Compared with control subjects, hyperhomocysteinemic subjects had elevated plasma levels of the CXC chemokines, epithelial neutrophil-activating peptide (ENA)-78 (P<0.05), and growth-regulated oncogene (GRO) (P=0.088), and homocysteine was significantly correlated with ENA-78 and GRO. (2) During folic acid treatment, normalization of homocysteine levels was accompanied by a marked reduction in oxidized low density lipoprotein–stimulated release of CXC chemokines (ie, GRO, ENA-78, and interleukin-8) and CC chemokines (ie, monocyte chemoattractant peptide-1 and RANTES) in peripheral blood mononuclear cells from these individuals. (3) The oxidized low density lipoprotein–induced release of ENA-78 from peripheral blood mononuclear cells from control subjects was significantly reduced when cells were incubated in the presence of folic acid. These data may suggest that homocysteine exerts atherogenic effects in part by enhancing chemokine responses in cells involved in atherogenesis and that folic acid supplementation may downregulate these inflammatory responses.

Key Words: homocysteine • folic acid • chemokines • peripheral blood mononuclear cells

This article has been cited by other articles:

				M. S. Nenseter, T. Ueland, K. Retterstol, E. Strom, L. Morkrid, S. Landaas, L. Ose, P. Aukrust, and K. B. Holven Dysregulated RANK Ligand/RANK Axis in Hyperhomocysteinemic Subjects: Effect of Treatment With B-Vitamins Stroke, January 1, 2009; 40(1): 241 - 247. [Abstract] [Full Text] [PDF]

				K. B. Holven, P. Aukrust, K. Retterstol, K. Otterdal, V. Bjerkeli, L. Ose, M. S. Nenseter, and B. Halvorsen The Antiatherogenic Function of HDL Is Impaired in Hyperhomocysteinemic Subjects J. Nutr., November 1, 2008; 138(11): 2070 - 2075. [Abstract] [Full Text] [PDF]

				J. M. Catov, L. M. Bodnar, R. B. Ness, N. Markovic, and J. M. Roberts Association of Periconceptional Multivitamin Use and Risk of Preterm or Small-for-Gestational-Age Births Am. J. Epidemiol., August 1, 2007; 166(3): 296 - 303. [Abstract] [Full Text] [PDF]

				K. B. Holven, B. Halvorsen, V. Bjerkeli, J. K. Damas, K. Retterstol, L. Morkrid, L. Ose, P. Aukrust, and M. S. Nenseter Impaired Inhibitory Effect of Interleukin-10 on the Balance Between Matrix Metalloproteinase-9 and Its Inhibitor in Mononuclear Cells From Hyperhomocysteinemic Subjects Stroke, July 1, 2006; 37(7): 1731 - 1736. [Abstract] [Full Text] [PDF]

				L. M Title, E. Ur, K. Giddens, M. J McQueen, and B. A Nassar Folic acid improves endothelial dysfunction in type 2 diabetes - an effect independent of homocysteine-lowering Vascular Medicine, May 1, 2006; 11(2): 101 - 109. [Abstract] [PDF]

				A. M. Gori, A. M. Corsi, S. Fedi, A. Gazzini, F. Sofi, B. Bartali, S. Bandinelli, G. F. Gensini, R. Abbate, and L. Ferrucci A proinflammatory state is associated with hyperhomocysteinemia in the elderly Am. J. Clinical Nutrition, August 1, 2005; 82(2): 335 - 341. [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]

				X. Zeng, J. Dai, D. G. Remick, and X. Wang Homocysteine Mediated Expression and Secretion of Monocyte Chemoattractant Protein-1 and Interleukin-8 in Human Monocytes Circ. Res., August 22, 2003; 93(4): 311 - 320. [Abstract] [Full Text] [PDF]

				B. Bayes, M. C. Pastor, J. Bonal, J. Junca, J. M. Hernandez, N. Riutort, A. Foraster, and R. Romero Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients Nephrol. Dial. Transplant., January 1, 2003; 18(1): 106 - 112. [Abstract] [Full Text] [PDF]