PMID- 24938465
OWN - NLM
STAT- MEDLINE
DCOM- 20150212
LR  - 20140618
IS  - 1676-5680 (Electronic)
IS  - 1676-5680 (Linking)
VI  - 13
IP  - 2
DP  - 2014 May 16
TI  - Homocysteine induces blood vessel global hypomethylation mediated by LOX-1.
PG  - 3787-99
LID - 10.4238/2014.May.16.2 [doi]
AB  - Homocysteine (Hcy) is an independent risk factor of atherosclerosis through its 
      involvement with the methionine cycle. In this study, we aimed to determine the 
      blood vessel global methylation rate in Hcy-induced atherosclerosis in 
      apolipoprotein-E-deficient (ApoE-/-) mice, and to explore the possible mechanism 
      of this change in endothelial cells. ApoE-/- mice were divided into a 
      hyperlipidemia (HLP) group, a hyperhomocysteinemia (HHcy) group, and an HHcy + 
      folate + vitamin B12 (HHcy+FA+VB) group. Wild-type C57BL/6J mice were prepared as 
      controls. Total Hcy, lipids, S-adenosylmethionine (SAM), and 
      S-adenosylhomocysteine (SAH) contents in serum were measured with an automatic 
      biochemistry analyzer and high-performance liquid chromatography. Methylation of 
      B1 repetitive elements in blood vessels was tested using nested 
      methylation-specific-polymerase chain reaction (nMS-PCR). Endothelial cells (ECs) 
      were pretreated with Hcy or by adding FA and VB. Lectin-like oxidized LDL 
      receptor-1 (LOX-1) expressions were determined by quantitative PCR, Western blot, 
      and nMS-PCR. The HHcy group displayed severe HLP and HHcy. SAM and SAH contents 
      were also elevated in the HHcy group compared with other groups. Methylation of 
      B1 repetitive elements was significantly increased in the HHcy group (0.5050 +/- 
      0.0182) compared to the HLP (0.5158 +/- 0.0163) and control (0.5589 +/- 0.0236) 
      groups. mRNA and protein expressions of LOX-1 increased (0.2877 +/- 0.0341, 0.6090 
      +/- 0.0547), whereas methylation expression decreased (0.5527 +/- 0.0148) after 100 
      muM Hcy stimulation in ECs. In conclusion, Hcy-induced atherosclerosis was closely 
      associated with induced hypomethylation status in the blood vessel, and this 
      process was partially mediated by LOX-1 DNA methylation.
FAU - Yang, X L
AU  - Yang XL
AD  - Department of Pathophysiology, Basic Medical School, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Tian, J
AU  - Tian J
AD  - Department of Pathophysiology, Basic Medical School, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Liang, Y
AU  - Liang Y
AD  - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Ma, C J
AU  - Ma CJ
AD  - Department of Clinical Examination, Ningxia Medical University, Yinchuan, 
      Ningxia, China.
FAU - Yang, A N
AU  - Yang AN
AD  - Department of Pathophysiology, Basic Medical School, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Wang, J
AU  - Wang J
AD  - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Ma, S C
AU  - Ma SC
AD  - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Cheng, Y
AU  - Cheng Y
AD  - Key Laboratory of Cardio-Cerebro-Vascular Diseases, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Hua, X
AU  - Hua X
AD  - Department of Pathophysiology, Basic Medical School, Ningxia Medical University, 
      Yinchuan, Ningxia, China.
FAU - Jiang, Y D
AU  - Jiang YD
AD  - Department of Pathophysiology, Basic Medical School, Ningxia Medical University, 
      Yinchuan, Ningxia, China yangwj04@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140516
PL  - Brazil
TA  - Genet Mol Res
JT  - Genetics and molecular research : GMR
JID - 101169387
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipids)
RN  - 0 (Olr1 protein, mouse)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics
MH  - Atherosclerosis/chemically induced/*genetics/pathology
MH  - Blood Vessels/drug effects/*metabolism
MH  - DNA Methylation/*genetics
MH  - Homocysteine/toxicity
MH  - Humans
MH  - Hyperhomocysteinemia/chemically induced/genetics/pathology
MH  - Hyperlipidemias/chemically induced/genetics/pathology
MH  - Lipids/blood
MH  - Mice
MH  - Scavenger Receptors, Class E/*genetics/metabolism
EDAT- 2014/06/19 06:00
MHDA- 2015/02/13 06:00
CRDT- 2014/06/19 06:00
PHST- 2014/06/19 06:00 [entrez]
PHST- 2014/06/19 06:00 [pubmed]
PHST- 2015/02/13 06:00 [medline]
AID - gmr3080 [pii]
AID - 10.4238/2014.May.16.2 [doi]
PST - epublish
SO  - Genet Mol Res. 2014 May 16;13(2):3787-99. doi: 10.4238/2014.May.16.2.