Hyperhomocysteinemia and atherosclerosis / 生理学报
Acta Physiologica Sinica
; (6): 103-114, 2005.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-334198
Biblioteca responsável:
WPRO
ABSTRACT
Arteriosclerosis and its complications, such as heart attack and stroke, are the major causes of death in developed countries. It was believed that age, hyperlipidemia, hypertension, diabetes and smoking are common risk factors for cardiovascular disease. In addition, overwhelming clinical and epidemiological studies have identified homocysteine (Hcy) as a significant and independent risk factor for cardiovascular disease. In healthy individuals, plasma Hcy is between 5 and 10 micromol/L. One cause of severe hypehomocys- teinemia (HHcy) is the deficiency of cystathionine beta-synthase (CBS), which converts Hcy to cystathionine. CBS homozygous deficiency results in severe HHcy with Hcy levels up to 100 to 500 micromol/L. Patients with severe HHcy usually present with neurological abnormalities, premature arteriosclerosis. It has been reported that lowering plasma Hcy improved endothelial dysfunction and reduced incidence of major adverse events after percutaneous coronary intervention. The mechanisms by which Hcy induces atherosclerosis are largely unknown. Several biological mechanisms have been proposed to explain cardiovascular pathological changes associated with HHcy. These include (1) endothelial cell damage and impaired endothelial function; (2) dysregulation of cholesterol and triglyceride biosynthesis; (3) stimulation of vascular smooth muscle cell proliferation; (4) thrombosis activation and (5) activation of monocytes. Four major biochemical mechanisms have been proposed to explain the vascular pathology of Hcy. These include (1) autooxidation through the production of reactive oxygen species; (2) hypomethylation by forming SAH, a potent inhibitor of biological transmethylations; (3) nitrosylation by binding to nitric oxide or (4) protein homocysteinylation by incorporating into protein. In summary, our studies, as well as data from other laboratories support the concept that Hcy is causally linked to atherosclerosis, and is not merely associated with the disease. Although folic acid, vitamin B12 and B6 can lower plasma Hcy levels, the long-term effects on cardiovascular disease risk are still unknown and judgments about therapeutic benefits await the findings of ongoing clinical trials.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Doença Cardiovascular
/
Doenças do Sistema Endócrino
/
Desnutrição e Deficiências Nutricionais
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Espécies Reativas de Oxigênio
/
Hiper-Homocisteinemia
/
Cistationina beta-Sintase
/
Aterosclerose
/
Genética
/
Homocisteína
/
Metabolismo
Tipo de estudo:
Estudo prognóstico
/
Fatores de risco
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Acta Physiologica Sinica
Ano de publicação:
2005
Tipo de documento:
Artigo