Homocysteine, hRIP3 and congenital cardiovascular malformations.

Elevated serum homocysteine (Hcys) levels have been suggested to contribute to congenital cardiovascular malformations, neural tube defects, and cardiovascular diseases. To investigate the mechanisms resulting in cardiovascular diseases and birth defects, Kuang-Hueih Chen et al. identified and characterized a novel gene, named rHCY2, whose expression was markedly up-regulated when Hcys was elevated in rat. In vivo, rHCY2 gene could induce chicken embryonic cells apoptosis and embryonic malformations. Its N-terminal kinase domain is apparently similar to human receptor-interacting serine-threonine kinase 3 (hRIP3). In view of this, we hypothesize that a link between the teratogenic effects of Hcys and hRIP3 is theoretically plausible. However, given the lack of data on the topic, it remains to be seen whether an elevated serum Hcys level will increase the expression of hRIP3. Using normal and abnormal human fetal hearts and cultured normal human fetal cardiomyocytes, we show that congenital cardiovascular malformations are associated with the overexpression of hRIP3, and evidence is found for a certain association between overexpression of hRIP3 and homocysteine-induced congenital cardiovascular malformations. Folic acid and anti-hRIP3 antibodies seem to favor maintenance of the shape and ultrastructure of cultured human fetal cardiomyocytes.