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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1596.)
© 2008 American Heart Association, Inc.

Brief Reviews

Murine Models of Hyperhomocysteinemia and Their Vascular Phenotypes

Sanjana Dayal; Steven R. Lentz

From the Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City.

Correspondence to Steven R. Lentz, MD, PhD, Department of Internal Medicine, C32 GH, The University of Iowa, Iowa City, IA 52242. E-mail steven-lentz{at}uiowa.edu

Series Editor: Daniel T. Eitzman
Regulation of Hemostasis and Thrombosis: Insights from Murine Models
ATVB In Focus

Preview Brief Reviews in this Series:

•Desch KC, Motto DG. Thrombotic thrombocytopenic purpura in humans and mice. Arterioscler Thromb Vasc Biol. 2007;27:1901–1908.
•Fay WP, Garg N, Sunkar M. Vascular functions of the plasminogen activation system. Arterioscler Thromb Vasc Biol. 2007;27:1231–1237.
•Denis CV, Wagner DD. Platelet adhesion receptors and their ligands in mouse models of thrombosis. Arterioscler Thromb Vasc Biol. 2007;27:728–739.
•Eitzman DT. Regulation of hemostasis and thrombosis: insights from murine models. Arterioscler Thromb Vasc Biol. 2007;27:453.

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 β-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.

Key Words: hyperhomocysteinemia • homocysteine • endothelium • thrombosis • murine models

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