Homocysteine and cerebral ischemia: pathogenic and therapeutical implications.
Curr Med Chem
; 14(3): 249-63, 2007.
Article
em En
| MEDLINE
| ID: mdl-17305530
ABSTRACT
Homocysteine is a thiol aminoacid synthesized during the metabolism of methionine. Increased plasma levels of homocysteine can be the result of mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine-beta synthase (CBS) and 5,10-methylenetetrahydrofolate reductase (MTHFR). Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or vitamin B12 (methylcobalamin), can induce hyperhomocysteinemia. Over the last decade, following in vitro and in vivo observations of a homocysteine-associated vascular pathology, convincing epidemiological evidence has been gathered on the relation between moderate elevation of plasma homocysteine and vascular disease, including cerebral ischemia. However, causality has yet to be established. The association between homocysteine and ischemic stroke might be a spurious epidemiological finding because of confounding or it might reflect reverse causality. If this is the case, elevated levels of plasma homocysteine should be interpreted as an epiphenomenon secondary to the vascular disease itself. Thus, whether lowering homocysteine concentration prevents cerebral ischemia remains to be determined. The only method to answer the question of the causal relation between homocysteine and ischemic stroke is by intervention trials in which patients at high vascular risk, such as those who have had a recent cerebral ischemic event are randomly allocated to placebo or homocysteine-lowering multivitamin therapy, and followed prospectively. Some of these randomized controlled trials are currently ongoing. Their results should hopefully resolve the issue in the next future.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Isquemia Encefálica
/
Homocisteína
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Curr Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Itália