Upregulation of SDF-1 is associated with atherosclerosis lesions induced by LDL concentration polarization.
Previous numerical simulations on low-density lipoprotein (LDL) concentration polarization in the arterial system indicated that LDL concentration polarization might play an important role in the genesis and development of atherosclerosis. To date, no in vivo experiments have examined this question directly, and the molecular mechanisms are unknown. In this study, ten rabbits were treated with gel-silica loop to develop a defined local stenosis in the straight segment of the left carotid artery. Both numerical simulation and experiment measurements showed that the concentration of LDL was about 35% higher at the blood/arterial wall interface than in the lumen on the distal side of the stenosis. Atherosclerotic lesions with abundant lipid deposits were observed and stromal derived factor-1 (SDF-1) was detected at the distal end of the stenosis, while the straight segment was plaque-free. In vitro studies demonstrated that LDL-induced SDF-1 expression in endothelial cells and increased monocyte adhesion to endothelial cells in a dose-dependent manner. The adhesion was suppressed when endothelial cells were pretreated with SDF-1 antibody. These results suggested LDL concentration polarization contributed to the localization of atherosclerosis and to the expression of SDF-1. In turn, SDF-1 facilitated plaque formation.
Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College of Chongqing University, Chongqing 400044, People's Republic of China.
Dangheng
D
Wei
Guixue
G
Wang
Chaojun
C
Tang
Juhui
J
Qiu
Jingbo
J
Zhao
Hans
H
Gregersen
Linhong
L
Deng
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D054377:Chemokine CXCL12 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D015854:Up-Regulation
D054377:Chemokine CXCL12; D008077:Lipoproteins, LDL