Degradation of α-actin filaments in venous smooth muscle cells in response to mechanical stretch

Jeremy Goldman*, Lin Zhong, Shu Q. Liu

*Corresponding author for this work

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Mechanical stretch has been shown to induce the degradation of α-actin filaments in smooth muscle cells (SMC) of experimental vein grafts. Here, we investigate the possible role of ERK1/2 and p38 MAPK in regulating this process using an ex vivo venous culture model that simulates an experimental vein graft. An exposure of a vein to arterial pressure induced a significant increase in the medial circumferential strain, which induced rapid α-actin filament disruption, followed by degradation. The percentage of SMC α-actin filament coverage was reduced significantly under arterial pressure (91 ± 1%, 43 ± 13%, 51 ± 5%, 28 ± 3%, and 19 ± 5% at 1, 6, 12, 24, and 48 h, respectively), whereas it did not change significantly in specimens under venous pressure at theses times. The degradation of SMC α-actin filaments paralleled an increase in the relative activity of caspase 3 (3.0 ± 0.7- and 1.7 ± 0.4-fold increase relative to the control level at 6 and 12 h, respectively) and a decrease in SMC density (from the control level of 1,368 ± 66 cells/mm2 at time 0 to 1,205 ± 90, 783 ± 129, 845 ± 61, 637 ± 55, and 432 ± 125 cells/mm2 at 1, 6, 12, 24, and 48 h of exposure to arterial pressure, respectively). Treatment with a p38 MAPK inhibitor (SB-203580) significantly reduced the stretch-induced activation of caspase 3 at 6 h (from 3.0 ± 0.7- to 2.2 ± 0.3-fold) in conjunction with a significant rescue of α-actin filament degradation (from 43 ± 13% to 69 ± 15%) at the same time. Treatment with an inhibitor for the ERK1/2 activator (PD-98059), however, did not induce a significant change in the activity of caspase 3 or the percentage of SMC α-actin filament coverage. These results suggest that p38 MAPK and caspase 3 may mediate stretch-dependent degradation of α-actin filaments in vascular SMCs.

Original languageEnglish (US)
Pages (from-to)H1839-H1847
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number5 53-5
DOIs
StatePublished - May 1 2003

Keywords

  • Caspase 3
  • Mitogen-activated protein kinases
  • Vascular grafts

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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