Apoptosis in serum-deprived vascular smooth muscle cells: evidence for cell volume-independent mechanism

S N Orlov, D Pchejetski, S Taurin, N Thorin-Trescases, G V Maximov, A V Pshezhetsky, A B Rubin, P Hamet

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28 Citations (Scopus)


Shrinkage is the earliest hallmark of cells undergoing apoptosis. This study examines the role of this phenomenon in the onset of vascular smooth muscle cell (VSMC) apoptosis triggered by growth factor withdrawal. In hyperosmotic media, VSMC showed the same amplitude of shrinkage but were more resistant to apoptosis than endothelial, epithelial and immune system cells. As with growth factor withdrawal, apoptosis in hyperosmotically-shrunken VSMC was sharply potentiated by transfection with E1A-adenoviral protein and was suppressed by activation of cAMP signaling as well as by the pan-caspase inhibitor z-VAD.fmk. Both cell shrinkage and apoptosis in VSMC-E1A treated with hyperosmotic medium were potentiated under sustained Na+, K+ pump inhibition with ouabain that was in contrast to inhibition of apoptosis documented in ouabain-treated, serum-deprived cells. After 1-hr incubation in serum-deprived medium, VSMC-E1A volume declined by approximately 15%. Transfer from hypotonic to control medium decreased VSMC-E1A volume by approximately 25% without any induction of apoptosis. Neither swelling in hyposmotic medium nor dissipation of the transmembrane gradient of K+ and major organic osmolytes protected serum-deprived VSMC-E1A from apoptosis. Thus, our results show that similarly to immune system, endothelial and epithelial cells, extensive VSMC shrinkage in hyperosmotic medium leads to the development of apoptosis. In contrast to hyperosmotic medium, the modest cell volume decrease occurring in serum-deprived VSMC does not contribute to triggering of the apoptotic machinery.
Original languageEnglish
Pages (from-to)55-66
Number of pages12
Issue number1
Publication statusPublished - Jan 2004


  • Adenoviridae
  • Adenovirus E1A Proteins
  • Amino Acid Chloromethyl Ketones
  • Animals
  • Aorta
  • Apoptosis
  • Caspase 3
  • Caspases
  • Cell Line
  • Cell Membrane
  • Cell Size
  • Chromatin
  • Colforsin
  • Culture Media, Serum-Free
  • Cyclic AMP
  • DNA
  • Dogs
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • Growth Substances
  • Kinetics
  • Mannitol
  • Microscopy, Fluorescence
  • Microscopy, Phase-Contrast
  • Muscle, Smooth, Vascular
  • Osmosis
  • Ouabain
  • Potassium
  • Rats
  • Sodium-Potassium-Exchanging ATPase
  • Time Factors
  • Transfection

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