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

American Journal of Physiology. Heart and Circulatory Physiology
Zhongbiao WangWalter H Newman

Abstract

Tumor necrosis factor (TNF)-alpha 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 ...Continue Reading

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Citations

Jul 7, 2007·Netherlands Heart Journal : Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation·S S M RensenG J J M van Eys
Jul 13, 2006·American Journal of Physiology. Renal Physiology·John A TaylorGeorge A Kuchel
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Mar 27, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Annika TaubeJuergen Eckel
Jun 5, 2020·American Journal of Hypertension·Fred S LambRyan J Stark
Jul 25, 2015·Journal of Cellular Physiology·Annunziata SciroccoCarola Severi
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