PMID- 15243582
OWN - NLM
STAT- MEDLINE
DCOM- 20050425
LR  - 20220414
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 11 Suppl 1
DP  - 2004 Jul
TI  - Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic 
      disease.
PG  - S56-64
AB  - 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.
FAU - Austin, R C
AU  - Austin RC
AD  - Department of Pathology and Molecular Medicine, McMaster University and the 
      Henderson Research Centre, Hamilton, Ontario, Canada. 
      raustin@thrombosis.hhscr.org
FAU - Lentz, S R
AU  - Lentz SR
FAU - Werstuck, G H
AU  - Werstuck GH
LA  - eng
GR  - HL62984/HL/NHLBI NIH HHS/United States
GR  - HL63943/HL/NHLBI NIH HHS/United States
GR  - NS24621/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Phlda1 protein, mouse)
RN  - 0 (Transcription Factors)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
CIN - Cell Death Differ. 2004 Jul;11 Suppl 1:S10-1. PMID: 15243579
MH  - Animals
MH  - Apoptosis/physiology
MH  - Arteriosclerosis/*etiology
MH  - Cardiovascular Diseases/etiology
MH  - Cell Adhesion/physiology
MH  - Endoplasmic Reticulum/metabolism/physiology
MH  - Endothelium, Vascular/metabolism/pathology/*physiopathology
MH  - Homocysteine/metabolism/physiology
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/physiopathology
MH  - Inflammation/etiology
MH  - Models, Biological
MH  - Oxidative Stress/physiology
MH  - Protein Folding
MH  - Risk Factors
MH  - Thrombosis/*etiology
MH  - Transcription Factors/chemistry/metabolism/physiology
RF  - 122
EDAT- 2004/07/10 05:00
MHDA- 2005/04/26 09:00
CRDT- 2004/07/10 05:00
PHST- 2004/07/10 05:00 [pubmed]
PHST- 2005/04/26 09:00 [medline]
PHST- 2004/07/10 05:00 [entrez]
AID - 4401451 [pii]
AID - 10.1038/sj.cdd.4401451 [doi]
PST - ppublish
SO  - Cell Death Differ. 2004 Jul;11 Suppl 1:S56-64. doi: 10.1038/sj.cdd.4401451.