PMID- 19656510
OWN - NLM
STAT- MEDLINE
DCOM- 20100303
LR  - 20240312
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Print)
IS  - 0021-9150 (Linking)
VI  - 208
IP  - 1
DP  - 2010 Jan
TI  - Anti-inflammatory and recycling properties of an apolipoprotein mimetic peptide, 
      Ac-hE18A-NH(2).
PG  - 134-41
LID - 10.1016/j.atherosclerosis.2009.07.019 [doi]
AB  - Apolipoprotein E (apoE) exerts prominent anti-inflammatory effects and undergoes 
      recycling by target cells. We previously reported that the peptide 
      Ac-hE18A-NH(2), composed of the receptor binding domain (LRKLRKRLLR) of apoE 
      covalently linked to the Class A amphipathic peptide 18A, dramatically lowers 
      plasma cholesterol and lipid hydroperoxides and enhances paraoxonase activity in 
      dyslipidemic animal models. The objective of this study was to determine whether 
      this peptide, analogous to apoE, exerts anti-inflammatory effects and undergoes 
      recycling under in vitro conditions. Pulse chase studies using 
      [(125)I]-Ac-hE18A-NH(2) in THP-1 derived macrophages and HepG2 cells showed 
      greater amounts of intact peptide in the cells at later time points indicating 
      recycling of the peptide. Ac-hE18A-NH(2) induced a 2.5-fold increase in 
      prebeta-HDL in the conditioned media of HepG2 cells. This effect persisted for 3 
      days after removal of the peptide from culture medium. Ac-hE18A-NH(2) also 
      induced the secretion of cell surface apoE from THP-1 macrophages. In addition, 
      the peptide increased cholesterol efflux from THP-1 cells by an ABCA1 independent 
      mechanism. Moreover, Ac-hE18A-NH(2) inhibited LPS-induced vascular cell adhesion 
      molecule-1 (VCAM-1) expression, and reduced monocyte adhesion in human umbilical 
      vein endothelial cells (HUVECs). It also reduced the secretion of interleukin-6 
      (IL-6) and monocyte chemoattractant protein-1 (MCP-1) from THP-1 macrophages even 
      when administered post-LPS and abolished the 18-fold increase in LPS-induced mRNA 
      levels for MCP-1 in THP-1 cells. Taken together, these results suggest that 
      addition of the putative apoE receptor-domain to the Class A amphipathic peptide 
      18A results in a peptide that, similar to apoE, recycles, thus enabling the 
      potentiation and prolongation of its anti-atherogenic and anti-inflammatory 
      effects. Such a peptide has great potential as a therapeutic agent in the 
      management of atherosclerosis and other inflammatory diseases.
CI  - Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
FAU - Datta, Geeta
AU  - Datta G
AD  - Department of Medicine, Atherosclerosis Research Unit, Division of Gerontology, 
      Geriatrics and Palliative Medicine, University of Alabama at Birmingham, 1808 
      Seventh Avenue South, Birmingham, AL 35294, USA. gdatta@uab.edu
FAU - White, C Roger
AU  - White CR
FAU - Dashti, Nassrin
AU  - Dashti N
FAU - Chaddha, Manjula
AU  - Chaddha M
FAU - Palgunachari, Mayakonda N
AU  - Palgunachari MN
FAU - Gupta, Himanshu
AU  - Gupta H
FAU - Handattu, Shaila P
AU  - Handattu SP
FAU - Garber, David W
AU  - Garber DW
FAU - Anantharamaiah, G M
AU  - Anantharamaiah GM
LA  - eng
GR  - HL084685/HL/NHLBI NIH HHS/United States
GR  - HL085282/HL/NHLBI NIH HHS/United States
GR  - R01 HL065663/HL/NHLBI NIH HHS/United States
GR  - DK070040/DK/NIDDK NIH HHS/United States
GR  - GM082952/GM/NIGMS NIH HHS/United States
GR  - HL65663/HL/NHLBI NIH HHS/United States
GR  - R01 DK070040/DK/NIDDK NIH HHS/United States
GR  - R01 GM082952/GM/NIGMS NIH HHS/United States
GR  - K08 HL085282/HL/NHLBI NIH HHS/United States
GR  - R01 GM082952-02/GM/NIGMS NIH HHS/United States
GR  - R01 HL084685/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090715
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Ac-hE18A-NH(2))
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (High-Density Lipoproteins, Pre-beta)
RN  - 0 (Lipoproteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cells, Cultured
MH  - High-Density Lipoproteins, Pre-beta/biosynthesis/drug effects
MH  - Humans
MH  - Inflammation/prevention & control
MH  - Lipoproteins/*pharmacology
MH  - Peptide Fragments/*pharmacology
MH  - Peptides/metabolism
MH  - Rabbits
MH  - Time Factors
PMC - PMC2813354
MID - NIHMS132430
EDAT- 2009/08/07 09:00
MHDA- 2010/03/04 06:00
PMCR- 2011/01/01
CRDT- 2009/08/07 09:00
PHST- 2008/12/21 00:00 [received]
PHST- 2009/06/11 00:00 [revised]
PHST- 2009/07/05 00:00 [accepted]
PHST- 2009/08/07 09:00 [entrez]
PHST- 2009/08/07 09:00 [pubmed]
PHST- 2010/03/04 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - S0021-9150(09)00547-4 [pii]
AID - 10.1016/j.atherosclerosis.2009.07.019 [doi]
PST - ppublish
SO  - Atherosclerosis. 2010 Jan;208(1):134-41. doi: 
      10.1016/j.atherosclerosis.2009.07.019. Epub 2009 Jul 15.