Homocysteine, folic acid and coronary artery disease: possible impact on prognosis and therapy.

Within the past four decades, the efforts of investigators worldwide have established the amino acid homocysteine (Hcy) as an important factor in arteriosclerosis and ageing. The amino acid homocysteine is a unique candidate for the study of different age-related pathological conditions, namely vascular diseases, dementia disorders and late-life depression, due to its multiple roles in different pathways leading to atherosclerosis and neurotoxicity. Especially, the role of homocysteine in predicting risk for atherothrombotic vascular disease has been evaluated in several observational studies in a large number of patients. These studies show that the overall risk for vascular disease is small, with prospective, longitudinal studies reporting a weaker association between homocysteine and atherothrombotic vascular disease compared to retrospective case-control and cross-sectional studies. Furthermore, randomised controlled trials of homocysteine-lowering therapy have failed to prove a causal relationship. On the basis of these results, there is currently insufficient evidence to recommend routine screening and treatment of elevated homocysteine concentrations with folic acid and other vitamins to prevent atherothrombotic vascular disease.

Hiperhomocisteinemia: fisiopatología y diagnóstico / Hyperhomocysteinemia: pathophysiology and diagnosis

La homocisteína es un aminoácido sulfurado intermediario del metabolismo de la metionina. La concentración plasmática, hiperhomocisteinemia que reviste mayor interés es la mayor tendencia a la trombosis arterial y venosa. Entre los mecanismos de daño asociados a la homocisteína se incluyen: toxicidad endotelial, aumento de la proliferación de las células del músculo liso, daño celular mediano por radicales libres, activación plaquetaria, trombosis y efectos en la matriz extracelular, entre otros. Los métodos de laboratorio para la medición de homocisteína en plasma son ELISA y HPLC, entre otros.

Effect of erythromycin on homocysteine-induced extracellular matrix metalloproteinase-2 production in cultured rat vascular smooth muscle cells.

BACKGROUND & OBJECTIVE: Several lines of evidence have shown an association between Chlamydia infection and atherosclerosis, but clinical trials of preventive antibiotic (erythromycin) treatment in patients with coronary artery disease have shown conflicting results. Hyperhomocysteinaemia is an independent risk factor of coronary artery disease and causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. In the present study we investigated the effects of erythromycin on the production of homocysteineinduced extracellular matrix metalloproteinase-2 (MMP-2) in cultured rat vascular smooth muscle cells (VSMCs). METHODS: Effects of different concentration of homocysteine (Hcy) (0-5000 micromol/l) on MMP-2 production, and the effects of different erythromycin concentrations (0-10 mmol/l) on homocysteine-induced MMP-2 production in cultured rat VSMCs were studied using gelatin zymography and Western blotting. The changes of MMP-2 under various treatments for 1, 3 and 5 days were also compared. RESULTS: Homocysteine (50-1000 mu mol/l) increased the production of MMP-2 significantly in a dose-dependent manner and reduced the production of MMP-2 at a high level (5000 mu mol/l). Increased production of MMP-2 induced by homocysteine was reduced by extracellularly added erythromycin in a dose-dependent manner. INTERPRETATION & CONCLUSION: Homocysteine increased the production of MMP-2 significantly in a dose-dependent manner. Extracellularly added erythromycin decreased homocysteine-induced MMP-2 secretion. The findings of the present study suggested that the beneficial effect of erythromycin on vascular disease processes might be due to its inhibitory effect on the Hcyinduced production of MMP-2 in VSMCs.

Vitamin B12 and folate depletion in cognition: a review.

In cross-sectional studies, low levels of folate and B12 have been shown to be associated with cognitive decline and dementia Evidence for the putative role of folate, vitamin B12 in neurocognitive and other neurological functions comes from reported cases of severe vitamin deficiencies, particularly pernicious anemia, and homozygous defects in genes that encode for enzymes of one-carbon metabolism. The neurological alterations seen in these cases allow for a biological role of vitamins in neurophysiology. Results are quite controversial and there is an open debate in literature, considering that the potential and differential role of folate and B12 vitamin in memory acquisition and cognitive development is not completely understood or accepted. What is not clear is the fact that vitamin B12 and folate deficiency deteriorate a pre-existing not overt pathological situation or can be dangerous even in normal subjects. Even more intriguing is the interaction between B12 and folate, and their role in developing hyperhomocysteinemia. The approach to the rehabilitation of the deficiency with adequate vitamin supplementation is very confusing. Some authors suggest it, even in chronic situations, others deny any possible role. Starting from these quite confusing perspectives, the aim of this review is to report and categorize the data obtained from the literature. Despite the plausible biochemical mechanism, further studies, based on clinical, neuropsychological, laboratory and (lastly) pathological features will be necessary to better understand this fascinating biochemical riddle.

Homocisteina y riñón: revisión bibliográfica / Homocyteine and kidney: bibliographic review

Se ha dado un creciente interés por la hiperhomocisteínemia como un factor de riesgo cardiovascular en personas jóvenes. En este artículo se realiza una revisión bibliográfica del metabolismo de la homocisteína, su alteración congénita y adquirida y el papel desde el punto de vista renal, su repercusión en pacientes con insuficiencia renal crónica así como su posible tratamiento