TY - JOUR
T1 - Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow
AU - Ni, Chih Wen
AU - Qiu, Haiwei
AU - Rezvan, Amir
AU - Kwon, Kihwan
AU - Nam, Douglas
AU - Son, Dong Ju
AU - Visvader, Jane E.
AU - Jo, Hanjoong
PY - 2010/10/14
Y1 - 2010/10/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77957935751&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-04-278192
DO - 10.1182/blood-2010-04-278192
M3 - Article
C2 - 20551377
AN - SCOPUS:77957935751
SN - 0006-4971
VL - 116
SP - e66-e73
JO - Blood
JF - Blood
IS - 15
ER -