Mechanisms of the atherogenic effects of elevated homocysteine in experimental models

Katina M Wilson; Steven R Lentz

doi:10.1055/s-2005-872401

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Journal article

Mechanisms of the atherogenic effects of elevated homocysteine in experimental models

Katina M Wilson and Steven R Lentz

Seminars in vascular medicine, Vol.5(2), pp.163-171

05/2005

DOI: 10.1055/s-2005-872401

PMID: 16047268

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Abstract

Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. During the last decade, considerable progress in delineating the mechanisms that underlie the atherogenic effects of hyperhomocysteinemia has been achieved through the use of experimental animal models. Among the most informative animal models are those that use genetic and dietary approaches to produce hyperhomocysteinemia in mice. Recent findings demonstrate that hyperhomocysteinemia can accelerate the development of atherosclerosis in susceptible models such as the apolipoprotein E-deficient mouse. Hyperhomocysteinemia also is a potent inducer of endothelial dysfunction, particularly in small vessels such as cerebral arterioles. Mechanisms of endothelial dysfunction may include inhibition of endothelial nitric oxide synthase by its endogenous inhibitor, asymmetric dimethylarginine, and oxidative inactivation of nitric oxide mediated by upregulation of prooxidant enzymes and downregulation of antioxidant enzymes. There also is good evidence from animal models that hyperhomocysteinemia produces endoplasmic reticulum stress, which may contribute to atherosclerosis and endothelial dysfunction by activating signal transduction pathways leading to inflammation, oxidative stress, and apoptosis.

Animals

Arteriosclerosis - blood

Arteriosclerosis - etiology

Arteriosclerosis - physiopathology

Disease Models, Animal

Endothelium, Vascular - metabolism

Endothelium, Vascular - physiopathology

Homocysteine - blood

Hyperhomocysteinemia - blood

Hyperhomocysteinemia - chemically induced

Hyperhomocysteinemia - complications

Methionine - toxicity

Mice

Nitric Oxide - metabolism

Oxidative Stress

Risk Factors

Details

Title: Subtitle: Mechanisms of the atherogenic effects of elevated homocysteine in experimental models
Creators: Katina M Wilson - University of Iowa
Steven R Lentz
Resource Type: Journal article
Publication Details: Seminars in vascular medicine, Vol.5(2), pp.163-171
DOI: 10.1055/s-2005-872401
PMID: 16047268
ISSN: 1528-9648
eISSN: 1529-3505
Grant note: HL63943 / NHLBI NIH HHS HL62984 / NHLBI NIH HHS NS24621 / NINDS NIH HHS
Language: English
Date published: 05/2005
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359826702771

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