PMID- 18364397
OWN - NLM
STAT- MEDLINE
DCOM- 20080812
LR  - 20211020
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 22
IP  - 7
DP  - 2008 Jul
TI  - Hyperhomocysteinemia induced by methionine supplementation does not independently 
      cause atherosclerosis in C57BL/6J mice.
PG  - 2569-78
LID - 10.1096/fj.07-105353 [doi]
AB  - A causal relationship between diet-induced hyperhomocysteinemia (HHcy) and 
      accelerated atherosclerosis has been established in apolipoprotein E-deficient 
      (apoE(-/-)) mice. However, it is not known whether the proatherogenic effect of 
      HHcy in apoE(-/-) mice is independent of hyperlipidemia and/or deficiency of 
      apoE. In this study, a comprehensive dietary approach using C57BL/6J mice was 
      used to investigate whether HHcy is an independent risk factor for accelerated 
      atherosclerosis or dependent on additional dietary factors that increase plasma 
      lipids and/or inflammation. C57BL/6J mice at 4 wk of age were divided into 6 
      dietary groups: chow diet (C), chow diet + methionine (C+M), western-type diet 
      (W), western-type diet + methionine (W+M), atherogenic diet (A), or atherogenic 
      diet + methionine (A+M). After 2, 10, 20, or 40 wk on the diets, mice were 
      sacrificed, and the levels of total plasma homocysteine, cysteine, and 
      glutathione, as well as total plasma cholesterol and triglycerides were analyzed. 
      Aortic root sections were examined for atherosclerotic lesions. HHcy was induced 
      in all groups supplemented with methionine, compared to diet-matched control 
      groups. Plasma total cholesterol was significantly increased in mice fed the W or 
      A diet. However, the W diet increased LDL/IDL and HDL levels, while the A diet 
      significantly elevated plasma VLDL and LDL/IDL levels without increasing HDL. No 
      differences in plasma total cholesterol levels or lipid profiles were observed 
      between methionine-supplemented groups and the diet-matched control groups. Early 
      atherosclerotic lesions containing macrophage foam cells were only observed in 
      mice fed the A or A + M diet. Furthermore, lesion size was significantly larger 
      in the A + M group compared to the A group at 10 and 20 wk; however, mature 
      lesions were never observed even after 40 wk on these diets. The presence of 
      lymphocytes, increased hyaluronan staining, and the expression of endoplasmic 
      reticulum (ER) stress markers were also increased in atherosclerotic lesions from 
      the A + M group. Taken together, these results suggest that HHcy does not 
      independently cause atherosclerosis in C57BL/6J mice even in the presence of 
      increased total plasma lipids induced by the W diet. However, HHcy can accelerate 
      atherosclerotic lesion development under dietary conditions that increase plasma 
      VLDL levels and/or inflammation.
FAU - Zhou, Ji
AU  - Zhou J
AD  - Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
FAU - Werstuck, Geoff H
AU  - Werstuck GH
FAU - Lhotak, Sarka
AU  - Lhotak S
FAU - Shi, Yuan Y
AU  - Shi YY
FAU - Tedesco, Vivienne
AU  - Tedesco V
FAU - Trigatti, Bernardo
AU  - Trigatti B
FAU - Dickhout, Jeffrey
AU  - Dickhout J
FAU - Majors, Alana K
AU  - Majors AK
FAU - DiBello, Patricia M
AU  - DiBello PM
FAU - Jacobsen, Donald W
AU  - Jacobsen DW
FAU - Austin, Richard C
AU  - Austin RC
LA  - eng
GR  - R01 HL052234/HL/NHLBI NIH HHS/United States
GR  - R37 HL052234/HL/NHLBI NIH HHS/United States
GR  - R37 HL052234-14/HL/NHLBI NIH HHS/United States
GR  - HL52234/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080325
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Lipids)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/blood/chemically induced/pathology/*physiopathology
MH  - Diet, Atherogenic
MH  - Dietary Supplements
MH  - Disease Models, Animal
MH  - Female
MH  - Homocysteine/blood
MH  - Hyaluronic Acid/metabolism
MH  - Hyperhomocysteinemia/blood/*chemically induced/pathology/*physiopathology
MH  - Immunohistochemistry
MH  - Lipids/blood
MH  - Methionine/administration & dosage/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
PMC - PMC2846632
MID - NIHMS184691
EDAT- 2008/03/28 09:00
MHDA- 2008/08/13 09:00
PMCR- 2010/03/29
CRDT- 2008/03/28 09:00
PHST- 2008/03/28 09:00 [pubmed]
PHST- 2008/08/13 09:00 [medline]
PHST- 2008/03/28 09:00 [entrez]
PHST- 2010/03/29 00:00 [pmc-release]
AID - fj.07-105353 [pii]
AID - 10.1096/fj.07-105353 [doi]
PST - ppublish
SO  - FASEB J. 2008 Jul;22(7):2569-78. doi: 10.1096/fj.07-105353. Epub 2008 Mar 25.