Zyxin mediation of stretch-induced gene expression in human endothelial cells.
BACKGROUND
Prolonged exposure to enhanced stretch, such as in hypertension, triggers endothelial dysfunction, a hallmark of pathological vascular remodeling processes. Despite its clinical relevance, little is known about stretch-induced gene expression in endothelial cells.


OBJECTIVE
Here, we have characterized a new stretch-inducible signaling pathway and the subsequent changes in endothelial gene expression in response to stretch.


RESULTS
Using human primary endothelial cells, we observed that the protein zyxin translocates from focal adhesions to the nucleus solely in response to stretch. There, it orchestrates complex changes in gene expression by interacting with a novel cis-acting element found in all zyxin-regulated genes analyzed so far. By way of DNA microarray pathway analyses, stretch-induced changes in endothelial cell gene expression were systematically explored, revealing that zyxin mainly regulates proinflammatory pathways.


CONCLUSIONS
Stretch appears to be an important factor in the development of endothelial dysfunction with zyxin as a potential therapeutic target to interfere with these early changes in endothelial cell phenotype.
Wójtowicz
Agnieszka
A
Division of Cardiovascular Physiology, University of Heidelberg, Im Neuenheimer Feld 326, Heidelberg, Germany.
Babu
Sahana Suresh
SS
Li
Li
L
Gretz
Norbert
N
Hecker
Markus
M
Cattaruzza
Marco
M
D050197:Atherosclerosis / Q000378:metabolism / Q000503:physiopathology; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D010641:Phenotype; D011311:Pressoreceptors; D015398:Signal Transduction / Q000502:physiology*; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology; D060589:Zyxin
D003598:Cytoskeletal Proteins; D006023:Glycoproteins; C092842:ZYX protein, human; D060589:Zyxin