PMID- 21670849
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20220331
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 17
IP  - 9-10
DP  - 2011 Sep-Oct
TI  - BRAP Activates Inflammatory Cascades and Increases the Risk for Carotid 
      Atherosclerosis.
PG  - 1065-74
LID - 10.2119/molmed.2011.00043 [doi]
AB  - The BRCA-1 associated protein gene (BRAP) was recently identified as a 
      susceptibility gene for myocardial infarction (MI). In the present study we aimed 
      to decipher the association between the BRAP polymorphism and carotid 
      atherosclerosis and the mechanism underlying its proatherogenic effect. A total 
      of 1749 stroke/MI-free volunteers received carotid ultrasonic examinations for 
      the measurement of intima-medial thickness (IMT) and plaque. The promoter 
      polymorphism rs11066001 was selected because it affects the transcription of 
      BRAP. We found that the GG genotype was associated with a 1.58-fold increased 
      risk for having at least one plaque compared to carrying the A allele (P = 
      0.021). When subjects were divided by the cutoff value of IMT above the mean plus 
      1 standard deviation, there was an overrepresentation of the GG genotype in the 
      subjects with thicker IMT (P = 0.004). The expression of BRAP increased 
      significantly when human aortic smooth muscle cells (HASMCs) were treated with 
      lipopolysaccharide (LPS). HASMCs were transfected with small interfering RNA 
      against BRAP or scrambled sequences before treatment with LPS. Knockdown of BRAP 
      led to attenuated HASMC proliferation and reduced secretion of monocyte 
      chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in response to LPS. 
      Downregulation of BRAP did not affect the protein levels of nuclear factor-kappaB 
      (NF-kappaB), but prohibited its nuclear translocation. Coimmunoprecipitation 
      experiments confirmed an interaction between BRAP and the two major components of 
      the IKK signalosome, IkappaBbeta and IKKbeta. Collectively, BRAP conferred a risk for 
      carotid plaque and IMT. Inflammatory stimuli upregulated BRAP expression, and 
      BRAP activated inflammatory cascades by regulating NF-kappaB nuclear translocation.
FAU - Liao, Yi-Chu
AU  - Liao YC
AD  - Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical 
      University, Kaohsiung, Taiwan Section of Neurology, Taichung Veterans General 
      Hospital, Taichung, Taiwan.
FAU - Wang, Yung-Song
AU  - Wang YS
FAU - Guo, Yuh-Cherng
AU  - Guo YC
FAU - Ozaki, Kouichi
AU  - Ozaki K
FAU - Tanaka, Toshihiro
AU  - Tanaka T
FAU - Lin, Hsiu-Fen
AU  - Lin HF
FAU - Chang, Ming-Hong
AU  - Chang MH
FAU - Chen, Ku-Chung
AU  - Chen KC
FAU - Yu, Ming-Lung
AU  - Yu ML
FAU - Sheu, Sheng-Hsiung
AU  - Sheu SH
FAU - Juo, Suh-Hang Hank
AU  - Juo SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110610
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (I kappa B beta protein)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.3.2.27 (BRAP protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - COS Cells
MH  - Carotid Artery Diseases/*genetics/metabolism/pathology
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Female
MH  - Gene Frequency
MH  - Genotype
MH  - HEK293 Cells
MH  - Humans
MH  - I-kappa B Proteins/genetics/metabolism
MH  - Inflammation/*genetics/metabolism/pathology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Myocytes, Smooth Muscle/drug effects/metabolism
MH  - *Polymorphism, Single Nucleotide
MH  - RNA Interference
MH  - Risk Factors
MH  - Tunica Intima/metabolism/pathology
MH  - Tunica Media/metabolism/pathology
MH  - Ubiquitin-Protein Ligases/*genetics/metabolism
MH  - Young Adult
PMC - PMC3188876
EDAT- 2011/06/15 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/06/10
CRDT- 2011/06/15 06:00
PHST- 2011/01/26 00:00 [received]
PHST- 2011/06/09 00:00 [accepted]
PHST- 2011/06/15 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/06/10 00:00 [pmc-release]
AID - molmed.2011.00043 [pii]
AID - 11_43_liao [pii]
AID - 10.2119/molmed.2011.00043 [doi]
PST - ppublish
SO  - Mol Med. 2011 Sep-Oct;17(9-10):1065-74. doi: 10.2119/molmed.2011.00043. Epub 2011 
      Jun 10.