PMID- 19776495
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20220331
IS  - 1880-3873 (Electronic)
IS  - 1340-3478 (Linking)
VI  - 16
IP  - 5
DP  - 2009 Oct
TI  - Poly (ADP-Ribose) polymerase inhibition attenuates atherosclerotic plaque 
      development in ApoE-/- mice with hyperhomocysteinemia.
PG  - 641-53
AB  - AIM: Hyperhomocysteinemia (Hhcy) is an important and independent risk factor for 
      atherosclerosis. Recent studies have shown that Poly (ADP-ribose) polymerase 
      (PARP) activation may be associated with Hhcy-induced endothelial dysfunction, 
      which is an important mechanism for Hhcy to affect atherosclerotic progress. 
      Thus, we investigated whether PARP inhibitors may attenuate atheroscle-rotic 
      plaque development in an Hhcy-induced experimental animal model with 
      atherosclerosis. METHODS: Six-week-old homozygous apolipoprotein E-deficient 
      (ApoE-/-) male mice fed a normal diet or high methionine diet randomly received 
      intraperitoneal injections of 10 mg/kg 3-aminoben-zamide (3-AB, a PARP inhibitor) 
      dissolved in phosphate-buffered saline (PBS), or physiological saline every other 
      day for 12 weeks. Atherosclerotic lesion sizes and PARP activity were measured. 
      Related inflammatory factors in atherogenesis were investigated by real-time 
      quantitative PCR and Western blot analysis. RESULTS: Our data demonstrated that 
      ApoE-/- mice fed a high methionine diet generated Hhcy, which subsequently 
      increased the atherosclerotic lesion size significantly, promoted oxidative 
      stress-associated DNA damage and PARP activation, then increased the expression 
      of proinflammatory fac-tors within atherosclerotic plaques. Although PARP 
      inhibition by 3-AB did not markedly inhibit plaque development in ApoE-/- mice 
      with spontaneous hyperlipidemia by feeding a normal diet, it significantly 
      reduced the atherosclerotic lesion size by 40% in Hhcy-induced atherosclerosis 
      without affecting plasma homocysteine levels and lipid contents, effectively 
      suppressed PARP activation, and inhibited nuclear translocation of nuclear 
      factor-(kappa)B (NF-(kappa)B) and subsequent production of inflam-matory factors, 
      such as vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattactant 
      protein-1 (MCP-1). CONCLUSION: Our results suggest that PARP inhibition 
      attenuates atherosclerotic plaque development under hyperhomocysteinemic 
      conditions, through the inhibition of PARP activation, nuclear NF-kappaB 
      translocation and subsequent expression of inflammatory factors.
FAU - Xie, Jiang-Jiao
AU  - Xie JJ
AD  - Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, 
      Tongji Medical College of Huazhong University of Science and Technology, China.
FAU - Yu, Xian
AU  - Yu X
FAU - Liao, Yu-Hua
AU  - Liao YH
FAU - Chen, Jian
AU  - Chen J
FAU - Yao, Rui
AU  - Yao R
FAU - Chen, Yong
AU  - Chen Y
FAU - Liao, Meng-Yang
AU  - Liao MY
FAU - Ding, Ying-Jun
AU  - Ding YJ
FAU - Tang, Ting-Ting
AU  - Tang TT
FAU - Cheng, Xiang
AU  - Cheng X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090924
PL  - Japan
TA  - J Atheroscler Thromb
JT  - Journal of atherosclerosis and thrombosis
JID - 9506298
RN  - 0 (Apolipoproteins E)
RN  - 0 (Benzamides)
RN  - 0 (DNA Primers)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - 8J365YF1YH (3-aminobenzamide)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/genetics/*physiology
MH  - Apoptosis/drug effects
MH  - Atherosclerosis/complications/*prevention & control
MH  - Base Sequence
MH  - Benzamides/*pharmacology
MH  - Blotting, Western
MH  - DNA Primers
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/*pharmacology
MH  - Hyperhomocysteinemia/*complications
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - *Poly(ADP-ribose) Polymerase Inhibitors
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Polymerase Chain Reaction
EDAT- 2009/09/25 06:00
MHDA- 2010/02/02 06:00
CRDT- 2009/09/25 06:00
PHST- 2009/09/25 06:00 [entrez]
PHST- 2009/09/25 06:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
AID - JST.JSTAGE/jat/1586 [pii]
AID - 10.5551/jat.1586 [doi]
PST - ppublish
SO  - J Atheroscler Thromb. 2009 Oct;16(5):641-53. doi: 10.5551/jat.1586. Epub 2009 Sep 
      24.