Cv. Serrano et al., Effect of simvastatin on monocyte adhesion molecule expression in patientswith hypercholesterolemia, ATHEROSCLER, 157(2), 2001, pp. 505-512
Citations number
33
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Increased monocyte adherence to the vessel wall is one of the earliest even
ts in atherosclerosis. The mechanism by which hypercholesterolemia causes a
lterations in endothelial adhesiveness for monocytes is unclear. This study
sought to determine if monocyte adhesion molecule expression is affected b
y low-density lipoprotein (LDL)-cholesterol levels. Patients with hyperchol
esterolemia and stable coronary artery disease were compared with those wit
hout major cardiovascular risk (control). Patients with hypercholesterolemi
a were treated with simvastatin 20-40 mg/day for 8-10 weeks. Blood samples
were examined with flow cytometry assays at baseline and after cholesterol-
lowering therapy. Monocyte CD11b and CD14 adhesion molecule expression, mea
sured as fluorescence intensity, were significantly (P < 0.0001) higher in
hypercholesterolemic patients before the study (176.9 +/- 9.8 and 138.0 +/-
4.8, respectively) when compared with that in control subjects (97.2 +/- 8
.1 and 84.0 +/- 6.4, respectively). Both decreased markedly with treatment:
to 118.8 +/- 6.9 and 103.1 +/- 3.9, respectively. Monocyte L-selectin expr
ession was significantly lower in patients with hypercholesterolemia before
treatment (43.0 +/- 3.0) when compared with control subjects (79.9 +/- 2.7
), and it increased markedly with treatment (54.2 +/- 2.5). LDL levels corr
elated directly with both CD11b and CD14 expression and correlated inversel
y with L-selectin expression. These data show that hypercholesterolemia aff
ects monocyte adhesion molecule expression which, in turn, decreases with s
tatin-induced plasmatic cholesterol reduction. Such perturbations in monocy
te function likely represent a proinflammatory response to hypercholesterol
emia and may have a role in the early progression of atherogenesis. (C) 200
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