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(Circulation Research. 2006;98:431.)
© 2006 American Heart Association, Inc.

Editorials

ApoA-I

A Missing Link Between Homocysteine and Lipid Metabolism?

Angela M. Devlin, Steven R. Lentz

From the Nutrition Research Program, Child & Family Research Institute, Department of Pediatrics (A.M.D.), University of British Columbia, Vancouver, Canada; the Department of Internal Medicine (S.R.L.), University of Iowa Carver College of Medicine, and the Veterans Affairs Medical Center (S.R.L.), Iowa City, Iowa.

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@uiowa.edu

See related article, pages 564–571

Key Words: cholesterol • homocysteine • lipoproteins

An extract of the first 250 words of the full text is provided, because this article has no abstract.

A link between homocysteine and atherothrombotic vascular disease was first suggested by McCully more than 30 years ago.¹ The vascular lesions observed by McCully in children with inborn errors of homocysteine metabolism were fibrotic rather than lipid rich, suggesting the possibility that hyperhomocysteinemia may produce vascular pathology through a mechanism independent of altered lipid metabolism. Since that time, many epidemiological studies have confirmed that elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of coronary events, stroke, and venous thromboembolism.^2–4 Most of the epidemiological data indicate that elevation of plasma tHcy is not associated with a significant change in plasma total cholesterol but is negatively associated with high density lipoprotein (HDL) cholesterol.^5–7 An effect of homocysteine on HDL metabolism could be clinically important, because HDL protects from vascular disease not only by facilitating reverse cholesterol transport⁸ but also through its direct antiinflammatory properties.⁹

During the past decade, the development of animal models has led to rapid progress in defining the pathophysiological consequences of hyperhomocysteinemia in vivo. Experimental approaches to induce hyperhomocysteinemia in animals include the use of diets that are high in methionine and/or low in folate, as well as genetic approaches, such as the generation of knockout mice with targeted disruption of the cystathionine ß-synthase (Cbs),¹⁰ methylene tetrahydrofolate reductase (Mthfr),¹¹ or methionine synthase (Mtr)¹² genes. Like hyperhomocysteinemic humans, hyperhomocysteinemic animals develop endothelial dysfunction, hepatic lipid accumulation, and decreased plasma HDL cholesterol with minimal changes in plasma total cholesterol.^13–15 Hyperhomocysteinemic . . . [Full Text of this Article]

Related Article:

Elevated Homocysteine Reduces Apolipoprotein A-I Expression in Hyperhomocysteinemic Mice and in Males With Coronary Artery Disease

Leonie G. Mikael, Jacques Genest, Jr, and Rima Rozen
Circ. Res. 2006 98: 564-571. [Abstract] [Full Text] [PDF]

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