Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin.
OBJECTIVE
This study sought to evaluate the effect of nLDL concentrations on monocyte adhesion molecule expression in hypercholesterolemic patients with stable coronary artery disease (CAD) and to determine whether lipid-lowering therapy with simvastatin would change this effect.


METHODS
Blood samples from patients with hypercholesterolemia (mean LDL 152 mg/dL) and CAD (HC, n = 23) were collected before and after a 12-week treatment with 40 mg of simvastatin. Healthy individuals (mean LDL 111 mg/dL) were used as controls (CT, n = 15). Isolated nLDL, at a fixed concentration of 100 mg/dL, was added to monocyte suspensions obtained before and after the simvastatin treatment. Monocyte activation was determined by changes in cellular adhesion molecule expression.


RESULTS
In response to nLDL, CD11b and CD14 adhesion molecule expression was higher in HC patients than in CT patients before treatment (174.2 +/- 8.4 vs 102.2 +/- 6.3, P < 0.03 and 140.4 +/- 5.0 vs 90.4 +/- 6.7, P < 0.04). After simvastatin treatment, CD11b expression decreased to 116.9 +/- 12.5 (P < 0.03) and CD14 expression to 107.5 +/- 6.2 (P < 0.04). Alternatively, L-selectin expression was lower in HC patients than in CT patients before therapy (46.0 +/- 3.5 vs 62.1 +/- 5.5, P < 0.04), and it increased markedly after lipid reduction to 58.7 +/- 5.0 (P < 0.04 vs baseline). After simvastatin treatment, LDL was reduced to mean 101.5 mg/dL.


CONCLUSIONS
These data demonstrate that monocytes from HC patients are more prone to marked nLDL-mediated changes of adhesion molecule expression than monocytes from controls. Simvastatin is capable of inhibiting such nLDL effects. This proinflammatory response to nLDL may have a role in the early onset of atherosclerosis.
Serrano
Carlos V
CV
Heart Institute (InCor) HCFMUSP, Medical School, University of São Paulo, São Paulo, SP, Brazil. carlos.serrano@incor.usp.br
Pesaro
Antônio Eduardo
AE
de Lemos
James A
JA
Rached
Fabiana
F
Segre
C Alexandre
CA
Gomes
Fernando
F
Ribeiro
Adriano F
AF
Nicolau
José Carlos
JC
Yoshida
Vanda M
VM
Monteiro
Hugo P
HP
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D039481:CD11b Antigen / Q000097:blood; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D019041:L-Selectin / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D018950:Lipopolysaccharide Receptors; D019041:L-Selectin; D019821:Simvastatin