PMID- 9187937
OWN - NLM
STAT- MEDLINE
DCOM- 19970804
LR  - 20180216
IS  - 0304-324X (Print)
IS  - 0304-324X (Linking)
VI  - 43 Suppl 1
DP  - 1997
TI  - Possible participation of Fas-mediated apoptosis in the mechanism of 
      atherosclerosis.
PG  - 35-42
AB  - Apoptosis is a programmed cell death that plays a major role during development, 
      homeostasis, and in many diseases. Recent evidence has demonstrated the death of 
      vascular smooth muscle cells (VSMCs) within advanced human atheroma. In the rat 
      balloon-injury model, apoptotic cells were specifically identified in the 
      neointima. The presence of apoptotic cells was demonstrated by in situ terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). To clarify 
      the mechanisms that trigger apoptosis in atherosclerotic lesions, we examined 
      whether cytokines released from macrophages can modulate Fas, a death signal, in 
      cultured human VSMCs. Simultaneous treatment with interleukin-1 (IL-1) and tumor 
      necrosis factor-alpha (TNF-alpha) but not with each cytokine alone induced 
      upregulation of Fas in VSMCs. However, coincubation with 
      NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, inhibited 
      the upregulation of Fas induced by IL-1 and TNF-alpha. Incubation with sodium 
      nitroprusside, a NO donor, also induced upregulation of Fas in VSMCs. 
      Furthermore, fluorescent nuclear staining with Hoechst 33258 revealed that 
      monoclonal antibody to human Fas significantly enhanced NO-induced apoptotis in 
      VSMCs. These findings suggest that macrophage-derived cytokines can induce 
      upregulation of Fas through a NO-dependent mechanism in VSMCs. Thus, Fas-mediated 
      apoptosis may regulate apoptotic death of VSMCs during atherogenesis.
FAU - Fukuo, K
AU  - Fukuo K
AD  - Department of Geriatric Medicine, Osaka University Medical School, Japan.
FAU - Nakahashi, T
AU  - Nakahashi T
FAU - Nomura, S
AU  - Nomura S
FAU - Hata, S
AU  - Hata S
FAU - Suhara, T
AU  - Suhara T
FAU - Shimizu, M
AU  - Shimizu M
FAU - Tamatani, M
AU  - Tamatani M
FAU - Morimoto, S
AU  - Morimoto S
FAU - Kitamura, Y
AU  - Kitamura Y
FAU - Ogihara, T
AU  - Ogihara T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Gerontology
JT  - Gerontology
JID - 7601655
RN  - 0 (Cytokines)
RN  - 0 (fas Receptor)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Antibody Specificity
MH  - Aorta/cytology/injuries
MH  - Apoptosis/*physiology
MH  - Arteriosclerosis/metabolism/*physiopathology
MH  - Carotid Arteries/cytology
MH  - Carotid Artery Injuries
MH  - Catheterization/adverse effects
MH  - Cytokines/pharmacology
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Macrophages/chemistry
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/metabolism/pathology
MH  - Nitric Oxide/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Up-Regulation/physiology
MH  - fas Receptor/immunology/*physiology
EDAT- 1997/01/01 00:00
MHDA- 1997/01/01 00:01
CRDT- 1997/01/01 00:00
PHST- 1997/01/01 00:00 [pubmed]
PHST- 1997/01/01 00:01 [medline]
PHST- 1997/01/01 00:00 [entrez]
AID - 10.1159/000213884 [doi]
PST - ppublish
SO  - Gerontology. 1997;43 Suppl 1:35-42. doi: 10.1159/000213884.