Rita Castro research interest’s concerns homocysteine, namely, its metabolism, genetic determinants and molecular mechanisms enrolled in its vascular pathogenecity. She investigated the molecular basis of inborn errors of homocysteine metabolism in Portugal and she have been studying the effect of variations in genes, directly or indirectly involved in the homocysteine metabolism, on the circulating levels of this amino acid. Her main area of interest is the understanding of the mechanisms through which homocysteine causes endothelial dysfunction and vascular disease. Using both in vitro and in vivo techniques, her work in this area showed that homocysteine indirectly modulates global DNA methylation patterns, via accumulation of its precursor (S-adenosylhomocysteine, AdoHcy), pointing to the importance of AdoHcy as a biomarker of genomic DNA methylation status. Ongoing research aims at characterizing the phenotype caused by AdoHcy accumulation in cultured human endothelial cells and animal models of atherosclerosis. Taking into account previous results it is postulated that epigenetic mechanisms can be implicated in the pathogenesis of atherosclerosis is mild hyperhomocysteinemia. As such, major goals are: (1) to unravel the molecular basis of the homocysteine-mediated demethylation processes ; and (2) to elucidate the putative effect of AdoHcy accumulation, via DNA, protein and RNA methylation changes, on the expression and activity of gene products involved in endothelial dysfunction.