Plasma cholesterol regulates soluble cell adhesion molecule expression in familial hypercholesterolemia.
BACKGROUND
Hypercholesterolemia is associated with endothelial dysfunction. On the basis of the hypothesis that high plasma cholesterol per se may be a sufficient stimulus to upregulate endothelial adhesiveness and that this phenomenon might be reversible, soluble endothelial leukocyte adhesion molecules (sELAMs) were studied in patients with familial hypercholesterolemia undergoing LDL apheresis.


RESULTS
Selective LDL absorption by dextran sulfate columns was used to treat plasma volumes of 6.5 to 9.2 L; after LDL apheresis, total cholesterol, LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) levels were reduced by 74%, 82%, 79%, 56%, and 86%, respectively. Soluble intercellular adhesion molecule-1 (sICAM-1) and sELAM- were measured before, immediately after, and 2 and 6 days after LDL apheresis. Basal sICAM-1 and sELAM-1 values were higher than in healthy control subjects. After LDL apheresis, they decreased (P<.0001 and P<.0004, respectively); their removal by extracorporeal circulation components was excluded. Individual pretreatment and posttreatment values of sICAM-1 and sELAM-1 were positively correlated (P<.0001 and P<.001, respectively) with total cholesterol; their rebound curves showed patterns similar to the total cholesterol rebound curve but not to the triglyceride and lipoprotein(a) curves.


CONCLUSIONS
In the absence of changes in clinical chemical parameters, tumor necrosis factor-alpha, interleukin-6, and acute-phase reactant proteins, these results confirm in a clinical setting the upregulation of endothelial adhesiveness observed in experimental hypercholesterolemia and suggest a direct role for cholesterol in regulating this phenomenon, at least in familial hypercholesterolemia.
Sampietro
T
T
CNR Institute of Clinical Physiology and S. Chiara Hospital, University of Pisa, Italy.
Tuoni
M
M
Ferdeghini
M
M
Ciardi
A
A
Marraccini
P
P
Prontera
C
C
Sassi
G
G
Taddei
M
M
Bionda
A
A
D000328:Adult; D001781:Blood Component Removal; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008078:Cholesterol, LDL; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol