Homocysteine and S-adenosylated metabolites in cardiovascular disease

Egidio Guglielmini, Maria Concetta Gueli

Risultato della ricerca: Other


A major unanswered question is whether direct cellular toxicity of homocysteine (Hcy) is causally involved in cardiovascular disease (CVD) in humans or whether homocysteinemia is simply a passive and indirect indicator of a more complex mechanism. Alternatively or additionally, the association between Hcy and CVD may result from its metabolic precursor S-adenosyl-Hcy (SAH), or from the altered ratio of S-adenosylmethionine SAM/SAH. This competition is based on the known effects of these adenosylated metabolites on cellular methylation, disturbances of which may lead to endothelial dysfunction and/ or CVD. Thus, it is of great significance to know how these adenosylated metabolites (SAM, SAH) and Hcy are interrelated, and how they relate to CVD. We measured SAM, SAH, their molar ratio, and tHcy in plasma and in red blood cells (RBCs) of 30 patients with proven CVD (age 64.2  8.4) and 29 healthy controls (age 61  7.5). Plasma and RBCs SAM, SAH and tHcy levels were measured by HPLC method.We soon confirmed a significant increased of plasma levels of tHcy, SAM, and SAH in patients compared to the controls (13.1 vs. 10.9 micromol/l; 134 vs. 62.0 nmol/l; 79.2 vs. 24.0 nmol/l, respectively), while the molar ratio of SAM/SAH was decreased in patients (1.69 vs. 2.58). In RBCs patients exhibited increased levels of SAH compared with controls (325 vs. 201 nmol/l) whereas SAM (3327 vs. 3635 nmol/l) and the molar ratio of SAM/SAH (10.2 vs. 18.0) were significantly decreased. Folic acid and vitamin B12 in plasma were similar in patients and controls. We suppose that what we noticed might be due to the lack of remethylation in RBCs additionally to the inhibition of transmethylation reactions by elevation of SAH. Since the ratio of SAM/SAH is strongly linked with the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients. This increased intracellular SAH, when occurs in endothelial cells, would lead to excessive endothelial apoptosis, which is both pro-atherogenic and pro-thrombotic. Together, these results point out the importance of remethylation pathway in CVD.
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2010
Pubblicato esternamente


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