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[Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data].
Pathol Biol (Paris) 2003; 51(2):101-10PB

Abstract

Recent epidemiological studies have suggested that hyperhomocysteinemia is associated with increased risk of vascular disease. Homocysteine is a sulphur-containing amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine which requires vitamin B6. The two pathways are coordinated by S-adenosylmethionine which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase (MTHFR) and as an activator of cystathionine beta-synthase (CBS). Hyperhomocysteinemia arises from disrupted homocysteine metabolism. Severe hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in CBS, MTHFR, or in enzymes involved in methyl cobalamine synthesis and homocysteine methylation. Mild hyperhomocysteinemia seen in fasting condition is due to mild impairment in the methylation pathway (i.e. folate or B12 deficiencies or MTHFR thermolability). Post-methionine-load hyperhomocysteinaemia may be due to heterozygous cystathionine-beta-synthase defect or B6 deficiency. Patients with homocystinuria and severe hyperhomocysteinemia develop arterial thrombotic events, venous thromboembolism, and more seldom premature arteriosclerosis. Experimental evidence suggests that an increased concentration of homocysteine may result in vascular changes through several mechanisms. High levels of homocysteine induce sustained injury of arterial endothelial cells, proliferation of arterial smooth muscle cells and enhance expression/activity of key participants in vascular inflammation, atherogenesis, and vulnerability of the established atherosclerotic plaque. These effects are supposed to be mediated through its oxidation and the concomitant production of reactive oxygen species. Other effects of homocysteine include: impaired generation and decreased bioavailability of endothelium-derived relaxing factor/nitric oxide; interference with many transcription factors and signal transduction; oxidation of low-density lipoproteins; lowering of endothelium-dependent vasodilatation. In fact, the effect of elevated homocysteine appears multifactorial affecting both the vascular wall structure and the blood coagulation system.

Authors+Show Affiliations

Laboratoire de physiologie, UFR de médecine, BP 87900, 21079 cedex, Dijon, France. jean-claude.guilland@chu-dijon.fr <jean-claude.guilland@chu-dijon.fr>No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

English Abstract
Journal Article
Review

Language

fre

PubMed ID

12801808

Citation

Guilland, J-C, et al. "[Hyperhomocysteinemia: an Independent Risk Factor or a Simple Marker of Vascular Disease?. 1. Basic Data]." Pathologie-biologie, vol. 51, no. 2, 2003, pp. 101-10.
Guilland JC, Favier A, Potier de Courcy G, et al. [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data]. Pathol Biol. 2003;51(2):101-10.
Guilland, J. C., Favier, A., Potier de Courcy, G., Galan, P., & Hercberg, S. (2003). [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data]. Pathologie-biologie, 51(2), pp. 101-10.
Guilland JC, et al. [Hyperhomocysteinemia: an Independent Risk Factor or a Simple Marker of Vascular Disease?. 1. Basic Data]. Pathol Biol. 2003;51(2):101-10. PubMed PMID: 12801808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data]. AU - Guilland,J-C, AU - Favier,A, AU - Potier de Courcy,G, AU - Galan,P, AU - Hercberg,S, PY - 2003/6/13/pubmed PY - 2003/9/3/medline PY - 2003/6/13/entrez SP - 101 EP - 10 JF - Pathologie-biologie JO - Pathol. Biol. VL - 51 IS - 2 N2 - Recent epidemiological studies have suggested that hyperhomocysteinemia is associated with increased risk of vascular disease. Homocysteine is a sulphur-containing amino acid whose metabolism stands at the intersection of two pathways: remethylation to methionine, which requires folate and vitamin B12 (or betaine in an alternative reaction); and transsulfuration to cystathionine which requires vitamin B6. The two pathways are coordinated by S-adenosylmethionine which acts as an allosteric inhibitor of the methylenetetrahydrofolate reductase (MTHFR) and as an activator of cystathionine beta-synthase (CBS). Hyperhomocysteinemia arises from disrupted homocysteine metabolism. Severe hyperhomocysteinemia is due to rare genetic defects resulting in deficiencies in CBS, MTHFR, or in enzymes involved in methyl cobalamine synthesis and homocysteine methylation. Mild hyperhomocysteinemia seen in fasting condition is due to mild impairment in the methylation pathway (i.e. folate or B12 deficiencies or MTHFR thermolability). Post-methionine-load hyperhomocysteinaemia may be due to heterozygous cystathionine-beta-synthase defect or B6 deficiency. Patients with homocystinuria and severe hyperhomocysteinemia develop arterial thrombotic events, venous thromboembolism, and more seldom premature arteriosclerosis. Experimental evidence suggests that an increased concentration of homocysteine may result in vascular changes through several mechanisms. High levels of homocysteine induce sustained injury of arterial endothelial cells, proliferation of arterial smooth muscle cells and enhance expression/activity of key participants in vascular inflammation, atherogenesis, and vulnerability of the established atherosclerotic plaque. These effects are supposed to be mediated through its oxidation and the concomitant production of reactive oxygen species. Other effects of homocysteine include: impaired generation and decreased bioavailability of endothelium-derived relaxing factor/nitric oxide; interference with many transcription factors and signal transduction; oxidation of low-density lipoproteins; lowering of endothelium-dependent vasodilatation. In fact, the effect of elevated homocysteine appears multifactorial affecting both the vascular wall structure and the blood coagulation system. SN - 0369-8114 UR - https://www.unboundmedicine.com/medline/citation/12801808/[Hyperhomocysteinemia:_an_independent_risk_factor_or_a_simple_marker_of_vascular_disease__1__Basic_data]_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0369811403001044 DB - PRIME DP - Unbound Medicine ER -