PMID- 19560954
OWN - NLM
STAT- MEDLINE
DCOM- 20091105
LR  - 20131121
IS  - 1096-7206 (Electronic)
IS  - 1096-7192 (Linking)
VI  - 98
IP  - 1-2
DP  - 2009 Sep-Oct
TI  - Hyperhomocysteinemia is associated with hypertriglyceridemia in mice with 
      methylenetetrahydrofolate reductase deficiency.
PG  - 187-94
LID - 10.1016/j.ymgme.2009.05.011 [doi]
AB  - Hyperhomocysteinemia (HHcy) can result from genetic or nutritional disturbances 
      in folate metabolism. The most common genetic cause of mild HHcy is 
      methylenetetrahydrofolate reductase (MTHFR) deficiency. To explore interactions 
      between HHcy and lipid metabolism in atherogenesis, we measured plasma 
      homocysteine (Hcy), triglycerides and cholesterol in Mthfr(+/+) and Mthfr(+/-) 
      mice on C57BL/6 and BALB/c backgrounds, fed control or folate-deficient diets. We 
      also crossed ApoE(C57)(-/-) mice with Mthfr(C57)(+/-) and Mthfr(BALB/c)(+/-) 
      mice, and examined the same plasma variables as well as lipid accumulation in 
      aortic sinus and whole aorta. Mthfr(+/-) mice had significantly higher plasma Hcy 
      and plasma triglycerides relative to Mthfr(+/+) mice. A significant positive 
      correlation was observed between plasma Hcy and plasma triglycerides in all mice. 
      Mthfr(+/-) mice had lower plasma ApoA-IV protein levels which could reduce 
      clearance of triglyceride-rich lipoproteins from the circulation. In the double 
      mutant experiments, plasma Hcy was higher in Mthfr(+/-) compared with Mthfr(+/+) 
      in ApoE(C57)(-/-)/Mthfr(C57) and ApoE(C57)(-/-)/Mthfr(BALB/c) mice. Triglycerides 
      in female ApoE(C57)(-/-)/Mthfr(BALB/c)(+/-) mice were higher than those in 
      ApoE(C57)(-/-)/Mthfr(BALB/c)(+/-) mice and correlated positively with Hcy. 
      ApoE(C57)(-/-)/Mthfr(C57)(+/-) male mice had more lipid deposition in aortic 
      sinus and whole aorta compared with ApoE(C57)(-/-)/Mthfr(c57)(+/+) mice. Our 
      results suggest that HHcy is associated with hypertriglyceridemia and that MTHFR 
      deficiency may exacerbate lipid accumulation in ApoE deficiency.
FAU - Mikael, Leonie G
AU  - Mikael LG
AD  - Departments of Human Genetics and Pediatrics, McGill University, Montreal 
      Children's Hospital, Que., Canada.
FAU - Wang, Xiao-Ling
AU  - Wang XL
FAU - Wu, Qing
AU  - Wu Q
FAU - Jiang, Hua
AU  - Jiang H
FAU - Maclean, Kenneth N
AU  - Maclean KN
FAU - Rozen, Rima
AU  - Rozen R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090623
PL  - United States
TA  - Mol Genet Metab
JT  - Molecular genetics and metabolism
JID - 9805456
RN  - 0 (Apolipoproteins E)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Triglycerides)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/deficiency
MH  - Cholesterol, HDL/blood
MH  - Female
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/blood/*complications/*enzymology
MH  - Hypertriglyceridemia/blood/*complications/*enzymology
MH  - Immunoblotting
MH  - Lipid Metabolism
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*deficiency/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Sinus of Valsalva/pathology
MH  - Triglycerides/blood
EDAT- 2009/06/30 09:00
MHDA- 2009/11/06 06:00
CRDT- 2009/06/30 09:00
PHST- 2009/05/22 00:00 [received]
PHST- 2009/05/22 00:00 [accepted]
PHST- 2009/06/30 09:00 [entrez]
PHST- 2009/06/30 09:00 [pubmed]
PHST- 2009/11/06 06:00 [medline]
AID - S1096-7192(09)00159-0 [pii]
AID - 10.1016/j.ymgme.2009.05.011 [doi]
PST - ppublish
SO  - Mol Genet Metab. 2009 Sep-Oct;98(1-2):187-94. doi: 10.1016/j.ymgme.2009.05.011. 
      Epub 2009 Jun 23.