Homocysteine and S-adenosylated metabolites in cardiovascular disease

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

Blood lipid, homocysteine, uric acid and vitamins in clinically stable Multiple Sclerosis patients

A decrease of antioxidants, of neuroprotective and immunoregulatory vitamins and an increase of total-Homocysteine, Cholesterol, HDL-cholesterol, and of cellular stress markers [1] was reported in patients affected by Multiple Sclerosis. Recently, considering their unreliability, mainly due to the variability of the samples investigated, the attention focused on clinical relapse that results associated to a decrease of Uric acid and an increase of Cholesterol and stress markers. Aim. To identify the biochemical status during Multiple Sclerosis (MS) in a phase of clinical stability (PCS), we compared the blood levels of Urico acid (UA), Folic acid (FA), vitamins B12, A, and E, total-Homocysteine (t-Hcy), total Cholesterol (CHL) , HDL-CHL, and Triglycerides (TG) in 20 MS stable patients with those of 40 healthy controls. Methods. Consecutive MS patients, with relapsing-remitting or secondary-progressive courses, in a (PCS), were included. Plasma t-Hcy levels were determined by Ubbink method [1]. Technicon Immuno autoanalyser was used for serum FA and vitamin B12 assays. HPLC and fluorometry were used for UA, vitamin A and E, CHL, HDL-CHL, and TG assays. The ratio of E/CHL was valued. Results and Discussions. We found that MS patients in a PCS have higher blood levels of vitamin B12, t-Hcy, CHL, and HDL-CHL and lower blood levels of vitamin E and of the ratio E/CHL. The blood level of UA, FA, vitamin A, and TG do not differ from controls during this phase of MS. The increased level of CHL could be expression of both an its increased synthesis by neural cells and a chronic damage of myelin and axons. HDL-CHL concentration might arise to counteract the increase of CHL and assure its transport to the liver. Plasma levels of vitamin E, the major hydrophobic chain-breaking antioxidant, are decreased and our data confirm and support the view that it is consumed to counterbalance MS chronic neurodegeneration. Also, the increased levels of t-Hcy and vitamin B12 match previous studies performed in MS patients outside relapse. No significant differences in UA, FA, vitamin A, and TG levels appeared, making unprobable their involvement in the degenerative process of the stable phase of MS