MILES R*, DALTON M, ROSENQUIST T, AND GADSON P

University of Nebraska Medical Center, Omaha, NE

Homocysteine is a sulfur-containing amino acid derived from the demethylation of methionine. Elevated blood homocysteine levels have been identified as an independent risk factor for cardiovascular disease. The mechanism for this involvement is not known. The increased risk for vascular disease begins at levels of plasma homocysteine that are only mildly elevated. We believe that this suggests an effect on intracellular signaling which alters the phenotype of vascular cells to promote or facilitate the development of disease. We have demonstrated that homocysteine can activate the redox-sensitive transcription factor c-Myb. In addition, over-expression of a clone with high homology to cytochrome oxidase in HTC cells increases the uptake of [³⁵S]-homocysteine and enhances the incorporation of [³H]-thymidine by HTC cells in response to homocysteine. We hypothesize that homocysteine binds to an oxidoreductase similar or identical to cytochrome oxidase to initiate redox signaling and functional cellular changes.