Leukocyte and endothelial adhesion molecules in patients with hypercholesterolemia: the effect of atorvastatin treatment.
Atherogenesis involves the migration of leukocytes into vascular subendothelial space, a process mediated by endothelial and leukocyte cell adhesion molecules. Endothelial molecules are assessed indirectly via serum levels, but leukocyte molecules can be assessed directly. We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules. We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment (20 mg/day). Expression of leukocyte integrins CD11a, CD11b, CD18, and CD49d and of L-selectin was measured by flow cytometry. Serum ICAM-1, E-selectin and von Willebrand factor were measured by ELISA. Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls, except for CD11a. Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b. In contrast, there was no effect of hypercholesterolemia and/or atorvastatin on the serum endothelial molecules. Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules. Our results support the role of increased leukocyte adhesiveness in atherogenesis.
Stulc
T
T
Third Department of Internal Medicine, Prague, Czech Republic. tstulc@lf1.cuni.cz
Vrablík
M
M
Kasalová
Z
Z
Marinov
I
I
Svobodová
H
H
Ceska
R
R
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D015815:Cell Adhesion Molecules / Q000097:blood / Q000187:drug effects*; D019040:E-Selectin / Q000097:blood / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D016023:Integrins / Q000097:blood / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D019041:L-Selectin / Q000097:blood / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D012016:Reference Values; D018709:Statistics, Nonparametric; D014841:von Willebrand Factor / Q000187:drug effects / Q000378:metabolism
D000924:Anticholesteremic Agents; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D006538:Heptanoic Acids; D016023:Integrins; D011758:Pyrroles; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D000069059:Atorvastatin