PMID- 12801608
OWN - NLM
STAT- MEDLINE
DCOM- 20031107
LR  - 20190718
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 168
IP  - 2
DP  - 2003 Jun
TI  - Effects of vitamin supplementation and hyperhomocysteinemia on atherosclerosis in 
      apoE-deficient mice.
PG  - 255-62
AB  - It has been demonstrated that hyperhomocysteinemia (HHcy) accelerates 
      atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. In this study, 
      vitamin-defined chow diets were used to induce HHcy in apoE(-/-) mice in an 
      attempt to identify possible pathogenic pathways. Six-week-old female apoE(-/-) 
      mice were divided into seven groups: vitamin-defined purified chow diet alone 
      (control), or same diet supplemented with either D,L-homocysteine (upward arrow 
      Hcy) or L-homocystine (upward arrow Hcy-Hcy), or diet high in L-methionine 
      (upward arrow Met), or diet high in B-vitamins (upward arrow vitamin), or diets 
      deficient in folate (downward arrow folate) or vitamin B(6) ( downward arrow 
      B(6)). Eighteen weeks later, plasma total homocysteine (tHcy), lipids and 
      atherosclerotic plaque burden (aortic root, aortic arch, and brachiocephalic 
      trunk) were measured. tHcy levels were similar in the upward arrow vitamin, 
      downward arrow folate, downward arrow B(6) and control groups (9.2-10.1 
      micromol/l, NS), but elevated mildly in the upward arrow Hcy-Hcy group (16.1 
      micromol/l) and moderately in the upward arrow Met and upward arrow Hcy groups 
      (53.6 and 51.5 micromol/l, respectively). Mice in the latter two groups had 
      significantly more atherosclerosis in the aortic root. Although B 
      vitamin-supplementation failed to lower tHcy levels, mice had less 
      atherosclerosis in the aortic arch. In summary, dietary methionine and 
      homocysteine, but not homocystine, enhanced the development of atherosclerosis. 
      Supplementation with B vitamins appeared to confer homocysteine-independent 
      protection against atherosclerosis. These results suggest that (1) there may be a 
      threshold level below which homocysteine is not atherogenic; (2) the atherogenic 
      effect of HHcy may be mediated via an intracellular pathway; and/or (3) the 
      anti-atherogenic effect of B vitamins in normohomocysteinemic mice is independent 
      of tHcy levels.
FAU - Zhou, Ji
AU  - Zhou J
AD  - Department of Cardiology, Aarhus University Hospital (Skejby), Aarhus, Denmark. 
      jzhou@thrombosis.hhscr.org
FAU - Moller, Jan
AU  - Moller J
FAU - Ritskes-Hoitinga, Merel
AU  - Ritskes-Hoitinga M
FAU - Larsen, Mogen L
AU  - Larsen ML
FAU - Austin, Richard C
AU  - Austin RC
FAU - Falk, Erling
AU  - Falk E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipids)
RN  - 0 (Vitamins)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Aorta/pathology
MH  - Apolipoproteins E/*deficiency
MH  - Arteriosclerosis/*etiology/pathology/*prevention & control
MH  - Brachiocephalic Trunk/pathology
MH  - Diet
MH  - *Dietary Supplements
MH  - Female
MH  - Homocysteine/administration & dosage/adverse effects/blood
MH  - Hyperhomocysteinemia/blood/*complications
MH  - Lipids/blood
MH  - Methionine/administration & dosage/adverse effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Vitamins/*pharmacology
EDAT- 2003/06/13 05:00
MHDA- 2003/11/08 05:00
CRDT- 2003/06/13 05:00
PHST- 2003/06/13 05:00 [pubmed]
PHST- 2003/11/08 05:00 [medline]
PHST- 2003/06/13 05:00 [entrez]
AID - S0021-9150(03)00138-2 [pii]
AID - 10.1016/s0021-9150(03)00138-2 [doi]
PST - ppublish
SO  - Atherosclerosis. 2003 Jun;168(2):255-62. doi: 10.1016/s0021-9150(03)00138-2.