Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

R C Austin; S R Lentz; G H Werstuck

doi:10.1038/sj.cdd.4401451

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Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

Journal article

Open access

Peer reviewed

Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease

R C Austin, S R Lentz and G H Werstuck

Cell death and differentiation, Vol.11 Suppl 1(S1), pp.S56-S64

07/01/2004

DOI: 10.1038/sj.cdd.4401451

PMID: 15243582

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Abstract

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease, including ischemic heart disease, stroke, and peripheral vascular disease. Mutations in the enzymes responsible for homocysteine metabolism, particularly cystathionine beta-synthase (CBS) or 5,10-methylenetetrahydrofolate reductase (MTHFR), result in severe forms of HHcy. Additionally, nutritional deficiencies in B vitamin cofactors required for homocysteine metabolism, including folic acid, vitamin B6 (pyridoxal phosphate), and/or B12 (methylcobalamin), can induce HHcy. Studies using animal models of genetic- and diet-induced HHcy have recently demonstrated a causal relationship between HHcy, endothelial dysfunction, and accelerated atherosclerosis. Dietary enrichment in B vitamins attenuates these adverse effects of HHcy. Although oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy, recent in vitro and in vivo studies demonstrate that HHcy induces endoplasmic reticulum (ER) stress, leading to activation of the unfolded protein response (UPR). This review summarizes the current role of HHcy in endothelial dysfunction and explores the cellular mechanisms, including ER stress, that contribute to atherothrombosis.

Details

Title: Subtitle: Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease
Creators: R C Austin - McMaster University
S R Lentz - University of Iowa
G H Werstuck - McMaster University
Resource Type: Journal article
Publication Details: Cell death and differentiation, Vol.11 Suppl 1(S1), pp.S56-S64
DOI: 10.1038/sj.cdd.4401451
PMID: 15243582
ISSN: 1350-9047
eISSN: 1476-5403
Language: English
Date published: 07/01/2004
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359803002771

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