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Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors.

Zeidan, Asad LU ; Nordström, Ina LU ; Albinsson, Sebastian LU ; Malmqvist, Ulf; Swärd, Karl LU and Hellstrand, Per LU (2003) In American Journal of Physiology: Cell Physiology 284(6). p.1387-1396
Abstract
Signaling mechanisms for stretch-dependent growth and differentiation of vascular smooth muscle were investigated in mechanically loaded rat portal veins in organ culture. Stretch-dependent protein synthesis was found to depend on endogenous release of angiotensin II. Autoradiography after [35S]methionine incorporation revealed stretch-dependent synthesis of several proteins, of which SM22 and actin were particularly prominent. Inhibition of RhoA activity by cell-permeant C3 toxin increased tissue mechanical compliance and reduced stretch-dependent extracellular signal-regulated kinase (ERK)1/2 activation, growth, and synthesis of actin and SM22, suggesting a role of the actin cytoskeleton. In contrast, inhibition of Rho-associated kinase... (More)
Signaling mechanisms for stretch-dependent growth and differentiation of vascular smooth muscle were investigated in mechanically loaded rat portal veins in organ culture. Stretch-dependent protein synthesis was found to depend on endogenous release of angiotensin II. Autoradiography after [35S]methionine incorporation revealed stretch-dependent synthesis of several proteins, of which SM22 and actin were particularly prominent. Inhibition of RhoA activity by cell-permeant C3 toxin increased tissue mechanical compliance and reduced stretch-dependent extracellular signal-regulated kinase (ERK)1/2 activation, growth, and synthesis of actin and SM22, suggesting a role of the actin cytoskeleton. In contrast, inhibition of Rho-associated kinase by Y-27632 did not reduce ERK1/2 phosphorylation or actin and SM22 synthesis and did not affect tissue mechanical compliance but still inhibited overall growth. The actin polymerization inhibitors latrunculin B and cytochalasin D both inhibited growth and caused increased tissue compliance. Whereas latrunculin B concentration-dependently reduced actin and SM22 synthesis, cytochalasin D did so at low (10-8 M) but not at high (10-6 M) concentration. The results show that stretch stabilizes the contractile smooth muscle phenotype. Stretch-dependent differentiation marker expression requires an intact cytoskeleton for stretch sensing, control of protein expression via the level of unpolymerized G-actin, or both. (Less)
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Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Cell Physiology
volume
284
issue
6
pages
1387 - 1396
publisher
American Physiological Society
external identifiers
  • wos:000182678000007
  • pmid:12734104
  • scopus:0038612851
ISSN
1522-1563
DOI
10.1152/ajpcell.00508.2002
language
English
LU publication?
yes
id
5c5ce5a0-6607-43ae-8621-572c8ac2a2a6 (old id 114174)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12734104&dopt=Abstract
date added to LUP
2007-06-26 13:35:43
date last changed
2018-01-07 09:49:35
@article{5c5ce5a0-6607-43ae-8621-572c8ac2a2a6,
  abstract     = {Signaling mechanisms for stretch-dependent growth and differentiation of vascular smooth muscle were investigated in mechanically loaded rat portal veins in organ culture. Stretch-dependent protein synthesis was found to depend on endogenous release of angiotensin II. Autoradiography after [35S]methionine incorporation revealed stretch-dependent synthesis of several proteins, of which SM22 and actin were particularly prominent. Inhibition of RhoA activity by cell-permeant C3 toxin increased tissue mechanical compliance and reduced stretch-dependent extracellular signal-regulated kinase (ERK)1/2 activation, growth, and synthesis of actin and SM22, suggesting a role of the actin cytoskeleton. In contrast, inhibition of Rho-associated kinase by Y-27632 did not reduce ERK1/2 phosphorylation or actin and SM22 synthesis and did not affect tissue mechanical compliance but still inhibited overall growth. The actin polymerization inhibitors latrunculin B and cytochalasin D both inhibited growth and caused increased tissue compliance. Whereas latrunculin B concentration-dependently reduced actin and SM22 synthesis, cytochalasin D did so at low (10-8 M) but not at high (10-6 M) concentration. The results show that stretch stabilizes the contractile smooth muscle phenotype. Stretch-dependent differentiation marker expression requires an intact cytoskeleton for stretch sensing, control of protein expression via the level of unpolymerized G-actin, or both.},
  author       = {Zeidan, Asad and Nordström, Ina and Albinsson, Sebastian and Malmqvist, Ulf and Swärd, Karl and Hellstrand, Per},
  issn         = {1522-1563},
  language     = {eng},
  number       = {6},
  pages        = {1387--1396},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Cell Physiology},
  title        = {Stretch-induced contractile differentiation of vascular smooth muscle: sensitivity to actin polymerization inhibitors.},
  url          = {http://dx.doi.org/10.1152/ajpcell.00508.2002},
  volume       = {284},
  year         = {2003},
}