PMID- 11011842
OWN - NLM
STAT- MEDLINE
DCOM- 20010208
LR  - 20220410
IS  - 0094-6176 (Print)
IS  - 0094-6176 (Linking)
VI  - 26
IP  - 3
DP  - 2000
TI  - Homocysteine, coagulation, platelet function, and thrombosis.
PG  - 243-54
AB  - Over the last 30 years, a growing body of evidence has documented the role of 
      hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the 
      mechanisms through which elevated circulating levels of homocysteine (Hcy) cause 
      vascular injury and promote thrombosis remain elusive. Most findings have been 
      achieved in in vitro studies employing exceedingly high concentrations of Hcy, 
      whereas only a few studies have been carried out in vivo in humans. In 
      homocystinuric patients, homozygotes for mutations of the gene coding for the 
      cystathionine beta-synthase enzyme, abnormalities of coagulation variables 
      reflecting a hypercoagulable state, have been reported. In vitro studies provide 
      a biochemical background for such a state. In homocystinuric patients, an in vivo 
      platelet activation has also been reported. The latter abnormality is not 
      corrected by the bolus infusion of concentrations of hirudin, which determines a 
      long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in 
      contrast, it appears at least in part lowered by the administration of the 
      antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive 
      oxygen species are generated. The latter initiate lipid peroxidation in cell 
      membranes (potentially responsible for endothelial dysfunction) and in 
      circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger 
      platelet activation as well as some of the hemostatic abnormalities reported in 
      such patients. Thus the oxidative stress induced by Hcy may be a key process in 
      the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in 
      cells (a consequence of high circulating levels of homocysteine) inhibits 
      methyltransferase enzymes, in turn preventing repair of aged or damaged cells. 
      This mechanism has been recently documented in patients with renal failure and 
      HHcy and provides an additional direction to be followed to understand the 
      tendency to thrombosis in moderate HHcy.
FAU - Coppola, A
AU  - Coppola A
AD  - Department of Clinical and Experimental Medicine, University of Naples Federico 
      II, Italy.
FAU - Davi, G
AU  - Davi G
FAU - De Stefano, V
AU  - De Stefano V
FAU - Mancini, F P
AU  - Mancini FP
FAU - Cerbone, A M
AU  - Cerbone AM
FAU - Di Minno, G
AU  - Di Minno G
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Semin Thromb Hemost
JT  - Seminars in thrombosis and hemostasis
JID - 0431155
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (oxidized low density lipoprotein)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 12001-79-5 (Vitamin K)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 979-92-0 (S-Adenosylhomocysteine)
RN  - EC 2.1.1.- (Methyltransferases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Arteriosclerosis/blood/epidemiology/etiology
MH  - Blood Coagulation/*physiology
MH  - Cardiovascular Diseases/epidemiology
MH  - Cellular Senescence
MH  - Child
MH  - Endothelium, Vascular/drug effects/metabolism
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Homocysteine/*metabolism/pharmacology
MH  - Homocystinuria/blood/complications/genetics
MH  - Humans
MH  - Hyperhomocysteinemia/blood/*complications
MH  - Lipid Peroxidation
MH  - Lipoproteins, LDL/blood
MH  - Male
MH  - Methyltransferases/antagonists & inhibitors
MH  - Oxidation-Reduction
MH  - Platelet Activation/*physiology
MH  - Reactive Oxygen Species
MH  - Renal Insufficiency/blood/complications
MH  - Risk Factors
MH  - S-Adenosylhomocysteine/metabolism
MH  - Thrombophilia/blood/epidemiology/*etiology
MH  - Thromboxane B2/blood
MH  - Vitamin K/administration & dosage/pharmacology
RF  - 62
EDAT- 2000/09/30 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/09/30 11:00
PHST- 2000/09/30 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/09/30 11:00 [entrez]
AID - 10.1055/s-2000-8469 [doi]
PST - ppublish
SO  - Semin Thromb Hemost. 2000;26(3):243-54. doi: 10.1055/s-2000-8469.