Published Online
on February 16, 2004

A more recent version of this article appeared on April 1, 2004

This Article Full Text (PDF) All Versions of this Article: 43/4/726    most recent 01.HYP.0000119189.82659.52v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cattaruzza, M. Articles by Hecker, M. Search for Related Content PubMed PubMed Citation Articles by Cattaruzza, M. Articles by Hecker, M. Related Collections Remodeling Hypertension - basic studies Resource utilization

Submitted on September 24, 2003
Revised on October 13, 2003

Focal Adhesion Protein Zyxin Is a Mechanosensitive Modulator of Gene Expression in Vascular Smooth Muscle Cells

Marco Cattaruzza; Claus Lattrich; and Markus Hecker^*

From the Department of Cardiovascular Physiology, University of Göttingen, Göttingen, Germany.

^* To whom correspondence should be addressed. E-mail: hecker{at}veg-physiol.med.uni-goettingen.de.

Abstract--Excessive deformation of vascular smooth muscle cells (SMCs) caused by a prolonged increase in blood pressure (eg, in hypertension) results in an adaptive remodeling of the vessel wall that is characterized by SMC hypertrophy or hyperplasia and contributes to fixation of the increase in blood pressure. The onset of this process is characterized by a unique change in gene expression in the SMC. However, thus far, no transcription factor has been identified that specifically mediates mechanosensitive gene expression in these cells. Therefore, the role of a putative mechanotransducer, the cytoskeletal protein zyxin, was investigated in rat aortic cultured SMCs. Immunofluorescence and Western blot analysis revealed that on exposure to cyclic stretch, but not to osmotic stress or treatment with proinflammatory cytokines, zyxin dissociates from focal adhesions and accumulates in the nucleus. Unlike zyxin, vinculin, another focal adhesion-associated protein, did not translocate. Moreover, antisense oligonucleotide downregulation of zyxin protein abundance suggested that zyxin accumulation in the nucleus is a prerequisite for mechanosensitive gene expression in these cells. Thus, stretch-induced endothelin B receptor expression, for example, was attenuated, whereas that of tenascin-C was augmented after zyxin suppression. The data are consistent with a role for zyxin in transducing mechanical stimuli from the cell membrane to the nucleus in vascular SMCs and in controlling the expression of mechanosensitive genes that have been implicated in hypertension-induced arterial remodeling.

Key words: vascular smooth muscle cells • gene expression • remodeling

This article has been cited by other articles:

				H. Schotman, L. Karhinen, and C. Rabouille Integrins mediate their unconventional, mechanical-stress-induced secretion via RhoA and PINCH in Drosophila J. Cell Sci., August 1, 2009; 122(15): 2662 - 2672. [Abstract] [Full Text] [PDF]

				H. Hirata, H. Tatsumi, and M. Sokabe Mechanical forces facilitate actin polymerization at focal adhesions in a zyxin-dependent manner J. Cell Sci., September 1, 2008; 121(17): 2795 - 2804. [Abstract] [Full Text] [PDF]

				W.-h. Guo and Y.-l. Wang Retrograde Fluxes of Focal Adhesion Proteins in Response to Cell Migration and Mechanical Signals Mol. Biol. Cell, November 1, 2007; 18(11): 4519 - 4527. [Abstract] [Full Text] [PDF]

				Y.-l. Wang Flux at Focal Adhesions: Slippage Clutch, Mechanical Gauge, or Signal Depot Sci. Signal., March 13, 2007; 2007(377): pe10 - pe10. [Abstract] [Full Text] [PDF]

				D. E. Ingber Cellular mechanotransduction: putting all the pieces together again FASEB J, May 1, 2006; 20(7): 811 - 827. [Abstract] [Full Text] [PDF]

				L. H. Romer, K. G. Birukov, and J. G.N. Garcia Focal Adhesions: Paradigm for a Signaling Nexus Circ. Res., March 17, 2006; 98(5): 606 - 616. [Abstract] [Full Text] [PDF]

				M. Yoshigi, L. M. Hoffman, C. C. Jensen, H. J. Yost, and M. C. Beckerle Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement J. Cell Biol., October 24, 2005; 171(2): 209 - 215. [Abstract] [Full Text] [PDF]

				G. Kojda and R. Hambrecht Molecular mechanisms of vascular adaptations to exercise. Physical activity as an effective antioxidant therapy? Cardiovasc Res, August 1, 2005; 67(2): 187 - 197. [Abstract] [Full Text] [PDF]