Kynurenic acid protects against the homocysteine-induced impairment of endothelial cells.

Kynurenic acid (KYNA) is a tryptophan metabolite produced in the kynurenine pathway. In the central nervous system, KYNA exerts neuroprotective and anticonvulsant effects by mechanisms associated with its antagonist activity against the ionotropic glutamate and alpha-7 nicotinic receptors. Its presence has been documented not only in cerebrospinal fluid and brain tissue, but also in the periphery. However, KYNA's function outside the brain has not been fully elucidated. In this study, experiments performed on bovine aorta endothelial cell cultures showed for the first time that KYNA exerts a protective activity against the homocysteine-induced impairment of endothelial cells. The addition of KYNA significantly increased endothelial cell migration and proliferation, which is diminished by homocysteine. KYNA also protected cells against homocysteine-induced cytotoxicity. Our data suggest that increasing KYNA levels in blood vessels may have a significant impact on the endothelium in hyperhomocysteinemia.