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Impaired homocysteine metabolism and atherothrombotic disease.
Lab Invest 2001; 81(5):645-72LI

Abstract

Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N(5,10)-methylenetetrahydrofolate reductase, and vitamin B(6) deficiency, perhaps associated with cystathionine beta-synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease.

Authors+Show Affiliations

L'Institut National de la Santé et de la Recherche Médicale, Biochimie des Lipoprotéines et Interactions Vasculaires, Faculté de Médecine, Université de Bourgogne, Dijon, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

11351038

Citation

Durand, P, et al. "Impaired Homocysteine Metabolism and Atherothrombotic Disease." Laboratory Investigation; a Journal of Technical Methods and Pathology, vol. 81, no. 5, 2001, pp. 645-72.
Durand P, Prost M, Loreau N, et al. Impaired homocysteine metabolism and atherothrombotic disease. Lab Invest. 2001;81(5):645-72.
Durand, P., Prost, M., Loreau, N., Lussier-Cacan, S., & Blache, D. (2001). Impaired homocysteine metabolism and atherothrombotic disease. Laboratory Investigation; a Journal of Technical Methods and Pathology, 81(5), pp. 645-72.
Durand P, et al. Impaired Homocysteine Metabolism and Atherothrombotic Disease. Lab Invest. 2001;81(5):645-72. PubMed PMID: 11351038.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired homocysteine metabolism and atherothrombotic disease. AU - Durand,P, AU - Prost,M, AU - Loreau,N, AU - Lussier-Cacan,S, AU - Blache,D, PY - 2001/5/15/pubmed PY - 2001/6/8/medline PY - 2001/5/15/entrez SP - 645 EP - 72 JF - Laboratory investigation; a journal of technical methods and pathology JO - Lab. Invest. VL - 81 IS - 5 N2 - Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N(5,10)-methylenetetrahydrofolate reductase, and vitamin B(6) deficiency, perhaps associated with cystathionine beta-synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease. SN - 0023-6837 UR - https://www.unboundmedicine.com/medline/citation/11351038/Impaired_homocysteine_metabolism_and_atherothrombotic_disease_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=11351038.ui DB - PRIME DP - Unbound Medicine ER -