There is evidence that mild elevations of tHcy are associated with an increased risk for occlusive
vascular disease,
thrombosis, and
stroke. It is hypothesized here that cellular toxicity could indirectly result from auto-oxidation of
homocysteine to
homocystine. Elevated levels of total plasma
homocysteine could be the primary cause of increased vascular risk, causing endothelial damage through a mechanism similar to that of
cystine precipitation, which is known to cause stone formation in
cystinosis and
cystinuria. In fact, only traces of
homocysteine circulate in plasma as the free
thiol; the remainder is present as oxidation products. Of these, the symmetric
disulfide homocystine is scarcely soluble at neutral pH. Its saturation limit is so close to the concentration of
homocysteine in normal plasma that a transient increase of
homocysteine levels could lead to precipitation of
homocystine microcrystals in the bloodstream. These could damage endothelial tissue, acting as a mechanic primer for subsequent prothrombotic blood vessel alterations.