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Aim: To investigate the changes in plasma level of the chemokine RANTES(regulated upon activation, normal T cells expressed and secreted) and the responsiveness of lipopolysaccharide (LPS)-induced RANTES secretion from monocytes in patients with hyperhomocysteinemia (HHcy). Methods: The plasma levels of homocysteine (Hcy), folate, and RANTES were measured in 38 control patients with normal Hcy levels and 40 patients with HHcy and the mRNA synthesis of RANTES in isolated human monocytes was determined by RNase protection assays. Results: The plasma level of RANTES was elevated in HHcy patients compared with controls (median 5.3 vs 3.5 ng/mL, P<0.01). LPS-induced RANTES production from monocytes of HHcy patients was also increased significantly. In addition, Hcy directly increased the mRNA level of RANTES in isolated normal human monocytes in a time- and dose-dependent manner.Conclusion: Upregulated RANTES from monocytes in HHcy patients may be involved in the atherogenesis of HHcy-induced atherosclerosis.