Murine models of hyperhomocysteinemia and their vascular phenotypes.
Hyperhomocysteinemia is an established risk factor for arterial as well as venous thromboembolism. Individuals with severe hyperhomocysteinemia caused by inherited genetic defects in homocysteine metabolism have an extremely high incidence of vascular thrombosis unless they are treated aggressively with homocysteine-lowering therapy. The clinical value of homocysteine-lowering therapy in individuals with moderate hyperhomocysteinemia, which is very common in populations at risk for vascular disease, is more controversial. Considerable progress in our understanding of the molecular mechanisms underlying the association between hyperhomocysteinemia and vascular thrombotic events has been provided by the development of a variety of murine models. Because levels of homocysteine are regulated by both the methionine and folate cycles, hyperhomocysteinemia can be induced in mice through both genetic and dietary manipulations. Mice deficient in the cystathionine beta-synthase (CBS) gene have been exploited widely in many studies investigating the vascular pathophysiology of hyperhomocysteinemia. In this article, we review the established murine models, including the CBS-deficient mouse as well as several newer murine models available for the study of hyperhomocysteinemia. We also summarize the major vascular phenotypes observed in these murine models.
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, USA.
Sanjana
S
Dayal
Steven R
SR
Lentz
D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000378:metabolism*; D020138:Hyperhomocysteinemia / Q000150:complications / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D010641:Phenotype; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology
D004791:Enzyme Inhibitors; D006710:Homocysteine; D050940:Betaine-Homocysteine S-Methyltransferase; C494549:Bhmt protein, mouse