PMID- 10623660
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 156
IP  - 1
DP  - 2000 Jan
TI  - Expression of cellular FLICE-inhibitory protein in human coronary arteries and in
      a rat vascular injury model.
PG  - 125-37
AB  - We previously isolated MACH-related inducer of toxicity (MRIT), a homolog of
      caspase 8. MRIT, also known as c-FLICE-inhibitory protein (c-FLIP), is an
      enzymatically inactive homolog of caspase 8 with homology to viral FLIP (v-FLIP).
      Because of this homology and resemblance to dominant negative proteins, c-FLIP is
      widely believed to be an antagonist to the death receptor-initiated apoptotic
      pathways that use caspase 8. We generated a polyclonal antibody, MAG1, and show
      that this antibody specifically recognizes two splice forms, long form (c-FLIPL) 
      and short form (c-FLIPS). By in situ hybridization and immunohistochemistry, we
      demonstrate that c-FLIP is expressed in endothelial cells, macrophages, and
      smooth muscle cells (SMCs) both in human coronary arteries and in cultured cells.
      In an uninjured rat carotid arteries, c-FLIP protein is abundant in the vascular 
      media. After balloon angioplasty, c-FLIP protein is rapidly down-regulated in
      medial SMCs for 2 weeks and regains expression by 4 weeks. In contrast, the
      neointima is strongly immunoreactive to c-FLIP from day 7 after the initial
      injury and remains strongly immunoreactive until 4 to 6 weeks. Similarly there is
      strong c-FLIP immunoreactivity in SMCs from nonatherosclerotic diffuse intimal
      thickening and in the overlying endothelial cells. In contrast, c-FLIP
      immunoreactivity is uneven and often absent in SMCs within the atherosclerotic
      plaque. Double labeling with c-FLIP antibody and terminal
      deoxynucleotidyltransferase-mediated UDP end labeling (TUNEL) in the injured rat 
      common carotid artery show that TUNEL-positive cells in the first 2 days after
      injury lack detectable c-FLIP, suggested a role for caspase 8 in this form of
      death. In contrast, there is no correlation of c-FLIP with the spontaneous
      elevation in death of intima seen at 7 days after injury. For human
      atherosclerotic plaques, the majority of TUNEL-positive cells lack detectable
      c-FLIP. The expression pattern of c-FLIP and the relation between c-FLIP and
      TUNEL suggest a role for c-FLIP- and caspase 8-driven death in control of
      viability of the cells of the atherosclerotic intima.
FAU - Imanishi, T
AU  - Imanishi T
AD  - Departments of Pathology, Medicine (Cardiology), and Molecular Biotechnology,
      University of Washington, Seattle, Washington 98195, USA.
FAU - McBride, J
AU  - McBride J
FAU - Ho, Q
AU  - Ho Q
FAU - O'Brien, K D
AU  - O'Brien KD
FAU - Schwartz, S M
AU  - Schwartz SM
FAU - Han, D K
AU  - Han DK
LA  - eng
GR  - HL26405/HL/NHLBI NIH HHS/United States
GR  - R37 HL026405/HL/NHLBI NIH HHS/United States
GR  - P01 HL003174/HL/NHLBI NIH HHS/United States
GR  - HL61860/HL/NHLBI NIH HHS/United States
GR  - HL03174/HL/NHLBI NIH HHS/United States
GR  - R01 HL026405/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein)
RN  - 0 (CFLAR protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Apoptosis/physiology
MH  - CASP8 and FADD-Like Apoptosis Regulating Protein
MH  - Carotid Artery Injuries/*metabolism/pathology
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Coronary Artery Disease/metabolism/pathology
MH  - Coronary Vessels/*metabolism/pathology/physiopathology
MH  - Endothelium, Vascular/metabolism/pathology
MH  - Female
MH  - Humans
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Macrophages/metabolism
MH  - Male
MH  - Middle Aged
MH  - Muscle, Smooth, Vascular/metabolism/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reference Values
PMC - PMC1868623
EDAT- 2000/01/07 00:00
MHDA- 2000/01/07 00:01
CRDT- 2000/01/07 00:00
PHST- 2000/01/07 00:00 [pubmed]
PHST- 2000/01/07 00:01 [medline]
PHST- 2000/01/07 00:00 [entrez]
AID - S0002-9440(10)64712-8 [pii]
AID - 10.1016/S0002-9440(10)64712-8 [doi]
PST - ppublish
SO  - Am J Pathol. 2000 Jan;156(1):125-37. doi: 10.1016/S0002-9440(10)64712-8.