Document Detail

Identification of CD44 as a senescence-induced cell adhesion gene responsible for the enhanced monocyte recruitment to senescent endothelial cells.
MedLine Citation:
PMID:  20382854     Owner:  NLM     Status:  MEDLINE    
The mechanism that is responsible for progression of atherosclerosis seen with increasing age remains controversial. This issue was addressed in the present study, by searching for genes that are uniquely expressed in senescent endothelial cells and functionally involved in inflammatory leukocyte adhesion recognized as a critical step in the initiation of atherogenesis. Senescent human umbilical vein endothelial cells (HUVECs) prepared by continuous subculturing in vitro showed higher binding affinity for monocytes (THP-1 cells, human acute monocytic leukemia cell line) compared with young cells. Gene expression profiles between young and senescent endothelial cells were compared by the cDNA microarray method, and CD44 was identified as one of the "senescence-induced cell adhesion genes" whose expression was upregulated in senescent cells and whose gene ontology annotation indicated their role in cell adhesion. The enhanced gene expression of CD44 in senescent endothelial cells was verified both at the mRNA and protein levels. Adhesion of monocytes to senescent endothelial cells was significantly reduced following pretreatment of endothelial cells with the CD44 antibody or small-interfering RNA, thus reinforcing the critical role of CD44 in the inflammatory event. Exogenous expression of CD44 in young HUVECs and in human aortic endothelial cells led to an increase in monocyte adhesion. CD44 expression levels in the rat aorta endothelium were found to increase in an age-dependent manner, as determined by immunohistochemistry and Western blotting. CD44 and other senescence-induced cell adhesion genes identified in this study may provide the novel targets for the prevention of inflammatory leukocyte adhesion leading to the development atherosclerosis.
Gyeong In Mun; Yong Chool Boo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-09
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  298     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H2102-11     Citation Subset:  IM    
Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
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MeSH Terms
Aging / genetics,  physiology
Antibodies / pharmacology
Antigens, CD44 / genetics*,  physiology
Atherosclerosis / physiopathology
Cell Adhesion / drug effects,  genetics,  physiology
Cell Aging / genetics*,  physiology
Cell Line, Tumor
Cells, Cultured
Endothelium, Vascular / cytology*,  drug effects,  physiology
Monocytes / cytology*,  drug effects,  physiology
RNA, Small Interfering / pharmacology
Umbilical Veins / cytology
Reg. No./Substance:
0/Antibodies; 0/Antigens, CD44; 0/CD44 protein, human; 0/RNA, Small Interfering

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