TNF-α induces proliferation or apoptosis in human saphenous vein smooth muscle cells depending on phenotype

Zhongbiao Wang, Pulipaka J. Rao, Manuel R Castresana, Walter H. Newman

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Tumor necrosis factor (TNF)-α is implicated in development of restenotic and atherosclerotic vascular lesions, which are pathological processes involving both proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Human VSMCs were recently found to contain heterogeneous subpopulations. We therefore examined whether TNF has different effects on distinct subpopulations of VSMCs. With the use of cloning techniques, two stable subpopulations of VSMCs were isolated from human saphenous vein: spindle- and epithelioid-shaped smooth muscle cells (Sp- and Ep-SMCs, respectively). We found that TNF stimulated growth in Sp-SMCs but had a toxic effect on Ep-SMCs. TNF did not induce apoptosis in Sp-SMCs as determined by nuclear staining and cellular DNA electrophoresis. In contrast, the reduction of viability in Ep-SMCs was associated with induction of apoptosis as characterized by cellular DNA fragmentation and nuclear condensation. Higher levels of the TNF-R1 receptor subtype were detected in membrane preparations from Ep-SMCs than in membranes from Sp-SMCs. Activation of caspase-3 was also selectively induced in Ep-SMCs but not in Sp-SMCs. Cycloheximide, an inhibitor of protein synthesis, enhanced the toxicity of TNF in Ep-SMCs. This effect of cycloheximide was not seen in Sp-SMCs. The data presented here demonstrate for the first time that TNF either promotes growth or induces apoptosis in human VSMCs depending on phenotype.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number1 57-1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Saphenous Vein
Smooth Muscle Myocytes
Vascular Smooth Muscle
Tumor Necrosis Factor-alpha
Apoptosis
Phenotype
Cycloheximide
Protein Synthesis Inhibitors
Membranes
Tumor Necrosis Factor Receptors
Poisons
DNA Fragmentation
Pathologic Processes
Growth
Caspase 3
Blood Vessels
Electrophoresis
Organism Cloning
Staining and Labeling
DNA

Keywords

  • Atherosclerosis
  • Cycloheximide
  • Epithelioid
  • Spindle
  • Stenosis
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology

Cite this

TNF-α induces proliferation or apoptosis in human saphenous vein smooth muscle cells depending on phenotype. / Wang, Zhongbiao; Rao, Pulipaka J.; Castresana, Manuel R; Newman, Walter H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 1 57-1, 01.01.2005.

Research output: Contribution to journalArticle

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