Simvastatin reduces the expression of adhesion molecules in circulating monocytes from hypercholesterolemic patients.
OBJECTIVE
The intercellular adhesion molecule-1 (ICAM-1/CD54) and its ligand, CD11a/CD18, mediate endothelial adhesion of leukocytes and their consecutive transmigration. Anti-inflammatory effects of statins are considered to be exerted in part through inhibition of leukocyte-endothelial interactions. We investigated the in vivo effects of simvastatin treatment in hypercholesterolemic patients and the influence of various statins on expression of cellular adhesion molecules in vitro.


RESULTS
A total number of 107 hypercholesterolemic patients were treated with 20 mg (n=52) or 40 mg (n=55) of simvastatin daily. After 6 weeks of treatment, peripheral blood mononuclear cells (PBMCs) expressed lower amounts of CD54-, CD18-, and CD11a-mRNA compared with pretreatment values. Surface expression of CD54 and CD18/CD11a on CD14+-monocytes also decreased significantly in both groups of patients. Moreover, simvastatin, atorvastatin, and cerivastatin were found to downregulate tumor necrosis factor (TNF)-alpha-induced expression of CD54 and CD18/CD11a in isolated PBMCs obtained from normal donors as well as TNF-alpha-dependent expression of these CAMs in cultured human umbilical vein endothelial cells (HUVECs). Furthermore, all three statins were found to reduce the binding of PBMCs to TNF-alpha-stimulated HUVECs in vitro.


CONCLUSIONS
Statin-induced inhibition of expression of CD54 and CD18/CD11a in PBMCs and HUVECs with consecutive loss of adhesive function may contribute to the anti-inflammatory effects of these drugs and some of their beneficial clinical activities.
Rezaie-Majd
Abdolreza
A
Clinic of Internal Medicine II, Department of Angiology, University of Vienna, Vienna, Austria.
Prager
Gerald W
GW
Bucek
Robert A
RA
Schernthaner
Gerit H
GH
Maca
Thomas
T
Kress
Hans-Georg
HG
Valent
Peter
P
Binder
Bernd R
BR
Minar
Erich
E
Baghestanian
Mehrdad
M
D000368:Aged; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects; D019821:Simvastatin / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014471:Umbilical Veins
D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D016169:Lymphocyte Function-Associated Antigen-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin