Carbamylated low-density lipoprotein induces monocyte adhesion to endothelial cells through intercellular adhesion molecule-1 and vascular cell adhesion molecule-1.
OBJECTIVE
Carbamylated low-density lipoprotein (LDL), the most abundant modified LDL isoform in human blood, has been recently implicated in causing the atherosclerosis-prone injuries to endothelial cells in vitro and atherosclerosis in humans. This study was aimed at testing the hypothesis that carbamylated LDL acts via inducing monocyte adhesion to endothelial cells and determining the adhesion molecules responsible for the recruitment of monocytes.


RESULTS
Exposure of human coronary artery endothelial cells with carbamylated LDL but not native LDL caused U937 monocyte adhesion and the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 adhesion molecules as measured by cell enzyme-linked immunosorbent assay. Silencing of intercellular adhesion molecule-1 by siRNA or its inhibition using neutralizing antibody resulted in decreased monocyte adhesion to the endothelial cells. Similar silencing or neutralizing of vascular cell adhesion molecule-1 alone did not have an effect but was shown to contribute to intercellular adhesion molecule-1 when tested simultaneously.


CONCLUSIONS
Taken together, these data provide evidence that intercellular adhesion molecule-1 in cooperation with vascular cell adhesion molecule-1 are essential for monocyte adhesion by carbamylated low-density lipoprotein-activated human vascular endothelial cells in vitro.
Apostolov
Eugene O
EO
Division of Nephrology, Department of Internal Medicine, University of Arkansas for Medical Sciences, 4301 W. Markham St, Little Rock, AR 72205, USA.
Shah
Sudhir V
SV
Ok
Ercan
E
Basnakian
Alexei G
AG
D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D003331:Coronary Vessels / Q000166:cytology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013997:Time Factors; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000502:physiology*
D000906:Antibodies; D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; D019010:Vascular Cell Adhesion Molecule-1; C039916:carbamyl-LDL; D018799:Intercellular Adhesion Molecule-1