PMID- 15830093
OWN - NLM
STAT- MEDLINE
DCOM- 20120628
LR  - 20131121
IS  - 0371-0874 (Print)
IS  - 0371-0874 (Linking)
VI  - 57
IP  - 2
DP  - 2005 Apr 25
TI  - Hyperhomocysteinemia and atherosclerosis.
PG  - 103-14
AB  - 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.
FAU - Yang, Fan
AU  - Yang F
AD  - Departments of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
FAU - Tan, Hong-Mei
AU  - Tan HM
FAU - Wang, Hong
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Review
PL  - China
TA  - Sheng Li Xue Bao
JT  - Sheng li xue bao : [Acta physiologica Sinica]
JID - 20730130R
RN  - 0 (Reactive Oxygen Species)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/etiology/*physiopathology
MH  - Cystathionine beta-Synthase/*deficiency/genetics
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/complications/*physiopathology
MH  - Reactive Oxygen Species/metabolism
EDAT- 2005/04/15 09:00
MHDA- 2012/06/29 06:00
CRDT- 2005/04/15 09:00
PHST- 2005/04/15 09:00 [pubmed]
PHST- 2012/06/29 06:00 [medline]
PHST- 2005/04/15 09:00 [entrez]
PST - ppublish
SO  - Sheng Li Xue Bao. 2005 Apr 25;57(2):103-14.