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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:8.)
© 2007 American Heart Association, Inc.

Editorials

Homocysteinylation of Metallothionein Impairs Intracellular Redox Homeostasis

The Enemy Within!

Stephen M. Colgan; Richard C. Austin

From the Henderson Research Centre, Hamilton, Ontario, Canada.

Correspondence to Dr Richard C. Austin, Henderson Research Centre, 60 Wing, Room 207, 711 Concession Street, Hamilton, Ontario, L8V 1C3. E-mail raustin@thrombosis.hhscr.org

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

Heart disease and stroke are major causes of death and morbidity in North America, and they exact high personal, community, and health care costs. Most heart attacks and strokes are caused by thrombosis superimposed on disrupted atherosclerotic lesions, a process known as atherothrombosis.^1,2 A number of risk factors are known to accelerate atherothrombosis, including hypercholesterolemia, smoking, diabetes, hypertension, and obesity. Numerous clinical and epidemiological studies have established hyperhomocysteinemia as an independent risk factor for cardiovascular disease and stroke.^3–8 Patients with inborn errors of methionine metabolism caused by deficiencies in cystathionine ß-synthase or 5,10-methylenetetrahydrofolate reductase present with severe hyperhomocysteinemia and have a 50% chance of developing a major vascular event by the age of 30 years if untreated.⁶ This vascular risk is substantially decreased by homocysteine-lowering therapy (dietary supplementation with folic acid, B-vitamins, and/or betaine), even if the treatment does not completely normalize total plasma homocysteine levels.⁸ Unlike severe hyperhomocysteinemia, mild hyperhomocysteinemia attributable to deficiencies in dietary folic acid and/or B-vitamins is common in the general population. Despite the association between hyperhomocysteinemia and increased cardiovascular risk, several recent clinical trials have failed to show a preventative benefit of homocysteine-lowering therapy in cardiovascular patients with mild hyperhomocysteinemia.^9,10 Although not completely understood, the results of these studies could imply that homocysteine-lowering therapy is ineffective in patients with established cardiovascular disease or that vitamin therapy has other, potentially adverse effects that neutralize its homocysteine-lowering benefit.¹¹

See page 49

A direct causal relationship between hyperhomocysteinemia and atherosclerosis has been reported in diet- and/or genetic-induced mouse . . . [Full Text of this Article]

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Targeting of Metallothionein by L-Homocysteine: A Novel Mechanism for Disruption of Zinc and Redox Homeostasis

John C. Barbato, Otilia Catanescu, Kelsey Murray, Patricia M. DiBello, and Donald W. Jacobsen
Arterioscler Thromb Vasc Biol 2007 27: 49-54. [Abstract] [Full Text] [PDF]

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