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Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow

Title
Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow
Authors
Ni C.-W.Qiu H.Rezvan A.Kwon K.Nam D.Son D.J.Visvader J.E.Jo H.
Ewha Authors
권기환조한중
SCOPUS Author ID
권기환scopus
Issue Date
2010
Journal Title
Blood
ISSN
0006-4971JCR Link
Citation
vol. 116, no. 15, pp. e66 - e73
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Recently, we showed that disturbed flow caused by a partial ligation of mouse carotid artery rapidly induces atherosclerosis. Here, we identified mechanosensitive genes in vivo through a genome-wide microarray study using mouse endothelial RNAs isolated from the flow-disturbed left and the undisturbed right common carotid artery. We found 62 and 523 genes that changed significantly by 12 hours and 48 hours after ligation, respectively. The results were validated by quantitative polymerase chain reaction for 44 of 46 tested genes. This array study discovered numerous novel mechanosensitive genes, including Lmo4, klk10, and dhh, while confirming well-known ones, such as Klf2, eNOS, and BMP4. Four genes were further validated for protein, including LMO4, which showed higher expression in mouse aortic arch and in human coronary endothelium in an asymmetric pattern. Comparison of in vivo, ex vivo, and in vitro endothelial gene expression profiles indicates that numerous in vivo mechanosensitive genes appear to be lost or dysregulated during culture. Gene ontology analyses show that disturbed flow regulates genes involved in cell proliferation and morphology by 12 hours, followed by inflammatory and immune responses by 48 hours. Determining the functional importance of these novel mechanosensitive genesmayprovide important insights into understanding vascular biology and atherosclerosis. © 2010 by The American Society of Hematology.
DOI
10.1182/blood-2010-04-278192
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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