PMID- 11742863
OWN - NLM
STAT- MEDLINE
DCOM- 20020103
LR  - 20190901
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 21
IP  - 12
DP  - 2001 Dec
TI  - Increased rate of apoptosis in intimal arterial smooth muscle cells through 
      endogenous activation of TNF receptors.
PG  - 1909-14
AB  - Intimal proliferation of smooth muscle cells (SMCs) is a key event in the 
      vascular response to injury, including the early stages of atherosclerosis and 
      restenosis after angioplasty. Tumor necrosis factor-alpha (TNF-alpha) has been 
      reported to stimulate growth of cultured human SMCs, but activation of TNF 
      receptors is also known to induce cell death by apoptosis. We report here that 
      SMCs isolated from the neointima of injured rat aortas are characterized by 
      increased expression of TNF-alpha in response to interleukin-1beta and 
      gamma-interferon compared with medial SMCs. Basal and serum-stimulated DNA 
      synthesis was higher in intimal than in medial SMCs. In contrast to previous 
      findings on human SMCs, exposure to interleukin-1beta/gamma-interferon or 
      TNF-alpha did not affect the growth of rat medial SMCs, inhibited DNA synthesis, 
      and decreased cell numbers in cultures of intimal SMCs. Incubation of intimal 
      SMCs with these cytokines also resulted in induction of terminal dUTP nick 
      end-labeling positivity and caspase-3 expression, suggesting cell death by 
      apoptosis, whereas medial cells were markedly less sensitive in this respect. 
      Cytokine-induced apoptosis in intimal cells was effectively inhibited by 
      treatment with antibodies against TNF receptors. These findings suggest that 
      endogenous activation of TNF receptors may represent a way to limit accumulation 
      of SMCs in injured arteries. This mechanism may also be important in SMC death in 
      advanced atherosclerotic plaques.
FAU - Niemann-Jonsson, A
AU  - Niemann-Jonsson A
AD  - Department of Medicine, Malmo University Hospital, Malmo, Sweden.
FAU - Ares, M P
AU  - Ares MP
FAU - Yan, Z Q
AU  - Yan ZQ
FAU - Bu, D X
AU  - Bu DX
FAU - Fredrikson, G N
AU  - Fredrikson GN
FAU - Branen, L
AU  - Branen L
FAU - Porn-Ares, I
AU  - Porn-Ares I
FAU - Nilsson, A H
AU  - Nilsson AH
FAU - Nilsson, J
AU  - Nilsson J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Interleukin-1)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-49-2 (DNA)
RN  - EC 3.4.22.- (CASP3 protein, human)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Caspase 3
MH  - Caspases/metabolism
MH  - Cells, Cultured
MH  - DNA/biosynthesis
MH  - Interferon-gamma/metabolism
MH  - Interleukin-1/metabolism
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Rats
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Tunica Intima/*metabolism
EDAT- 2001/12/18 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/12/18 10:00
PHST- 2001/12/18 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/12/18 10:00 [entrez]
AID - 10.1161/hq1201.100222 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):1909-14. doi: 
      10.1161/hq1201.100222.