Hyperhomocysteinemia, thrombosis and vascular biology.
Epidemiological evidence suggests that hyperhomocysteinemia (HH) is an independent risk factor for arterial thrombotic diseases such as acute myocardial infarction, stroke, peripheral ischemic occlusive disorders as well as venous thromboembolism. This article presents a hypothesis to explain the pathogenesis of increases in plasma homocysteine level and associated increased risk of thrombotic disease. It is based on the data in the literature and results from our laboratory on the impact of folate induced HH in rats. These results include: a) Effects on whole blood coagulation, which is characterized by increased velocity of coagulation, increased firmness of the formed coagulum and prolonged initiation phase of the coagulation; b) Genetic regulation of blood cells, which is characterized by increased platelet activation, impaired fibrinolysis and impaired function of the contact activation pathway of coagulation, and c) Reduced functional activities of single coagulation factors FXII:C, FX:C and FII:C.
Ebbesen
L S
LS
Clinical Institute and Department of Clinical Biochemistry, University Hospital of Aarhus, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark. lse@dadlnet.dk
D000818:Animals; D001777:Blood Coagulation; D001808:Blood Vessels / Q000473:pathology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005342:Fibrinolysis; D005494:Folic Acid Deficiency / Q000097:blood; D005786:Gene Expression Regulation; D006710:Homocysteine / Q000097:blood / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000473:pathology*; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015539:Platelet Activation; D051381:Rats; D012306:Risk; D013916:Thrombelastography; D013927:Thrombosis / Q000473:pathology*; D013997:Time Factors; D014652:Vascular Diseases / Q000473:pathology
D006710:Homocysteine