PMID- 16931800
OWN - NLM
STAT- MEDLINE
DCOM- 20061012
LR  - 20240322
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 99
IP  - 6
DP  - 2006 Sep 15
TI  - Hyperhomocysteinemia decreases circulating high-density lipoprotein by inhibiting 
      apolipoprotein A-I Protein synthesis and enhancing HDL cholesterol clearance.
PG  - 598-606
AB  - We previously reported that hyperhomocysteinemia (HHcy), an independent risk 
      factor of coronary artery disease (CAD), is associated with increased 
      atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) 
      in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) 
      mice. We observed that plasma homocysteine (Hcy) concentrations are negatively 
      correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We 
      found the loss of large HDL particles, increased HDL-free cholesterol, and 
      decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol 
      efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. 
      ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was 
      unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the 
      levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in 
      mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase 
      (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and 
      plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the 
      clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in 
      CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and 
      unchanged ATP-binding cassette transporter A1 protein expression in the liver. 
      These findings indicate that HHcy inhibits reverse cholesterol transport by 
      reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing 
      HDL-C clearance.
FAU - Liao, Dan
AU  - Liao D
AD  - Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
FAU - Tan, Hongmei
AU  - Tan H
FAU - Hui, Rutai
AU  - Hui R
FAU - Li, Zhaohui
AU  - Li Z
FAU - Jiang, Xiaohua
AU  - Jiang X
FAU - Gaubatz, John
AU  - Gaubatz J
FAU - Yang, Fan
AU  - Yang F
FAU - Durante, William
AU  - Durante W
FAU - Chan, Lawrence
AU  - Chan L
FAU - Schafer, Andrew I
AU  - Schafer AI
FAU - Pownall, Henry J
AU  - Pownall HJ
FAU - Yang, Xiaofeng
AU  - Yang X
FAU - Wang, Hong
AU  - Wang H
LA  - eng
GR  - K02 HL074925/HL/NHLBI NIH HHS/United States
GR  - HL74925/HL/NHLBI NIH HHS/United States
GR  - HL30914/HL/NHLBI NIH HHS/United States
GR  - R01 HL077288/HL/NHLBI NIH HHS/United States
GR  - R01 HL030914/HL/NHLBI NIH HHS/United States
GR  - HL59314/HL/NHLBI NIH HHS/United States
GR  - HL74966/HL/NHLBI NIH HHS/United States
GR  - R01 HL074966/HL/NHLBI NIH HHS/United States
GR  - HL77288/HL/NHLBI NIH HHS/United States
GR  - HL67033/HL/NHLBI NIH HHS/United States
GR  - P01 HL059314/HL/NHLBI NIH HHS/United States
GR  - P50 HL059314/HL/NHLBI NIH HHS/United States
GR  - HL36045/HL/NHLBI NIH HHS/United States
GR  - R01 HL036045/HL/NHLBI NIH HHS/United States
GR  - R01 HL067033/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060824
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Apolipoprotein A-I)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Lipoproteins, HDL)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 375YFJ481O (Cystathionine)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
CIN - Circ Res. 2006 Sep 15;99(6):565-6. PMID: 16973911
MH  - Aged
MH  - Animals
MH  - Apolipoprotein A-I/antagonists & inhibitors/*biosynthesis
MH  - Apolipoproteins E/deficiency
MH  - Biological Transport
MH  - Cells, Cultured
MH  - Cholesterol/metabolism
MH  - Cholesterol, HDL/*metabolism
MH  - Coronary Artery Disease/etiology
MH  - Cystathionine/deficiency
MH  - Hepatocytes/metabolism
MH  - Homocysteine/blood
MH  - Humans
MH  - Hyperhomocysteinemia/blood/*metabolism
MH  - Lipoproteins, HDL/*blood
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Middle Aged
PMC - PMC4400841
MID - NIHMS677913
EDAT- 2006/08/26 09:00
MHDA- 2006/10/13 09:00
PMCR- 2015/04/17
CRDT- 2006/08/26 09:00
PHST- 2006/08/26 09:00 [pubmed]
PHST- 2006/10/13 09:00 [medline]
PHST- 2006/08/26 09:00 [entrez]
PHST- 2015/04/17 00:00 [pmc-release]
AID - 01.RES.0000242559.42077.22 [pii]
AID - 10.1161/01.RES.0000242559.42077.22 [doi]
PST - ppublish
SO  - Circ Res. 2006 Sep 15;99(6):598-606. doi: 10.1161/01.RES.0000242559.42077.22. 
      Epub 2006 Aug 24.