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Am J Physiol Cell Physiol 284: C1387-C1396, 2003. First published January 29, 2003; doi:10.1152/ajpcell.00508.2002
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Vol. 284, Issue 6, C1387-C1396, June 2003

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

Asad Zeidan, Ina Nordström, Sebastian Albinsson, Ulf Malmqvist, Karl Swärd, and Per Hellstrand

Division of Molecular and Cellular Physiology, Department of Physiological Sciences, Biomedical Center, Lund University, SE-221 84 Lund, Sweden

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.

SM22; cytoskeleton; rat portal vein; RhoA; hypertension


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