Homocyst(e)inemia in daily practice

Malinow, M. R.; Sexton, Gary; Averbuch, M; Grossman, Milton S.; Wilson, David P.; Upson, B.

doi:10.1097/00019501-199003000-00010

Cited by 118 publications

(5 citation statements)

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“…Heterozygotes typically have much less marked hyperhomocysteinemia with plasma homocysteine concentrations in the range of 20 to 40 mmol/L, approximately two to four times greater than the normal concentration of homocysteine in plasma. [7][8][9][10] Severe hyperhomocysteinemia occurs in homozygous deficiency of N,N10-methylenetetrahydrofolate reductase, the enzyme involved in the vitamin B 12 -dependent remethylation of homocysteine to methionine, may also lead to severe hyperhomocysteinemia. 11 Patients with this type of deficiency tend to have a worse prognosis than those with cystathionine β-synthase deficiency, in part because of the complete lack of effective therapy.…”

Section: Discussionmentioning

confidence: 99%

Recurrent Unprovoked Venous Thromboembolism in a Young Female Patient with High Levels of Homocysteine

2012

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Hyperhomocysteinemia is a rare condition which predisposes to atherothrombosis. Recurrent venous thromboembolism (VTE) with hyperhomocysteinemia is known but extremely uncommon. Homocysteine levels of more than 22 umol/L can predispose to VTE in a middle-aged women. We describe a case of a middle-aged woman, community ambulant with recurrent VTE with intermediately high homocysteine levels. She had no other risk factors for recurrent venous thrombosis. In our article, we also discuss hyperhomocysteinemia and its link to VTE.

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Section: Discussionmentioning

confidence: 99%

Recurrent Unprovoked Venous Thromboembolism in a Young Female Patient with High Levels of Homocysteine

2012

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“…Hyperhomocysteinemia, a condition that arises from disrupted Hcy metabolism, is caused by both genetic and dietary disorders and has been implicated in the pathophysiology of atherosclerosis [3]. Moderate hyperhomocysteinemia has been found in 20–30% of patients with coronary and peripheral vascular disease and levels of Hcy may be as high as 200–300 μM in homocysteinuria [4,5]. Hcy is a sulphur‐containing amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12, and trans‐sulphuration to cystathionine, which requires pyridoxal‐5′‐phosphate [6].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have shown that Hcy evokes adverse vascular effects by promoting oxidative damage to endothelial cells [1,7]. These cytotoxic effects appear to be caused by an increased production of hydrogen peroxide during the auto‐oxidation of the sulfhydryl group and may account for the observed endothelial dysfunction mediated by elevated Hcy levels [4–6]. Alteration of the vascular responses of normal endothelial cells by Hcy has also been attributed to the high reactivity of this metabolite with nitric oxide (NO) [1,8].…”

Section: Introductionmentioning

confidence: 99%

Homocysteine attenuates endothelial haem oxygenase‐1 induction by nitric oxide (NO) and hypoxia

et al. 2001

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The disrupted metabolism of homocysteine (Hcy) causes hyperhomocysteinemia, a condition associated with the impairment of nitric oxide (NO) bio-availability, tissue hypoxia and increased risk of vascular disease. Here, we examined how Hcy modulates the induction of the stress protein haem oxygenase-1 (HO-1) evoked by NO releasing agents and hypoxia in vascular endothelial cells. We found that Hcy (0.5 mM) markedly reduced the increase in haem oxygenase activity and HO-1 protein expression induced by sodium nitroprusside (SNP, 0.5 mM) but did not affect HO-1 activation mediated by S-nitroso-N-acetyl-penicillamine. Cells pre-treated with Hcy followed by addition of fresh medium containing SNP still exhibited an augmented haem oxygenase activity. Interestingly, high levels of Hcy were also able to abolish hypoxia-mediated HO-1 expression in a concentration-dependent manner. These novel findings indicate that hyperhomocysteinemia interferes with crucial signaling pathways required by cells to respond and adapt to stressful conditions. ß

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“…Several studies have found that patients with premature coronary artery disease have significantly higher levels of homocyst(e)ine than control subjects (3)(4)(5)(6)(7)(8). Although the role…”

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confidence: 99%

Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.

Watanabe

Osada

Aratani

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

537

518

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Studies by various investigators have indicated that elevated levels of plasma homocyst(e)ine are strongly associated with the occurrence of occlusive vascular diseases. With the eventual aim of determining whether or not elevated plasma homocyst(e)ine concentrations are directly causative of cardiovascular diseases, we have generated mice that are moderately and severely homocyst(e)inemic. Homologous recombination in mouse embryonic stem cells was used to inactivate the cystathionine 13-synthase [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22] gene. Homozygous mutants completely lacking cystathionine 13-synthase were born at the expected frequency from matings ofheterozygotes, but they suffered from severe growth retardation and a majority of them died within 5 weeks after birth. Histological examination showed that the hepatocytes of homozygotes were enlarged, multinucleated, and filled with microvesicular lipid droplets. Plasma homocyst(e)ine levels of the homozygotes were "40 times normal. These mice, therefore, represent a model for severe homocyst(e)inemia resulting from the complete lack of cystathionine 18-synthase. Heterozygous mutants have 509o reduction in cystathionine 8-synthase mRNA and enzyme activity in the liver and have twice normal plasma homocyst(e)ine levels. Thus, the heterozygous mutants are promising for studying the in vivo role of elevated levels of homocyst(e)ine in the etiology of cardiovascular diseases.Homocysteine is an intermediate amino acid in methionine metabolism and is either converted to cysteine by transsulfuration or methylated to form methionine. A decreased rate of metabolism through either of these pathways can lead to homocyst(e)inemia and homocystinuria.The of elevated homocyst(e)ine in the formation of thrombi or in the acceleration of atherogenesis is not well understood, various experiments suggest that homocysteine is a mediator of disease. For example, homocysteine damages cultured human venous and arterial endothelial cells (9, 10). Furthermore, DeGroot et al. (11) showed that cells grown from obligate heterozygotes for CBS deficiency were much more sensitive to methionine-mediated injury than were control cells. Other in vitro studies have demonstrated that homocysteine enhances autooxidation of low density lipoproteins (12), enhances biosynthesis of thromboxane (13), inhibits cell-surface thrombomodulin expression (14), promotes vascular smooth muscle cell growth (15), and enhances binding of lipoprotein(a) to fibrin (16). In vivo, long-term infusion of homocystine in baboons leads to endothelial desquamation, to an increase in platelet consumption, and to arterial lesions (17). However, there are also conflicting data indicating that an increased incidence of vascular diseases was not found in individuals heterozygous for homocystinuria (18,19). Determining whether elevated plasma homocyst(e)ine levels are causative of cardiovascular disease or are a consequence of the disease has been difficult because of the lack of an experimental animal mo...

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Homocyst(e)inemia in daily practice

Cited by 118 publications

References 0 publications

Recurrent Unprovoked Venous Thromboembolism in a Young Female Patient with High Levels of Homocysteine

Recurrent Unprovoked Venous Thromboembolism in a Young Female Patient with High Levels of Homocysteine

Homocysteine attenuates endothelial haem oxygenase‐1 induction by nitric oxide (NO) and hypoxia

Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia.

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