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Native LDL-Cholesterol Mediated Monocyte Adhesion Molecule Overexpression is Blocked by Simvastatin

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Abstract

Aim of the study

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.

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Authors and Affiliations

  1. Heart Institute (InCor) HCFMUSP, Medical School, University of São Paulo, Av. Enéas C. de Aguiar, 44, São Paulo, SP, 05403-000, Brazil

    Carlos V. Serrano Jr., Antônio Eduardo Pesaro, Fabiana Rached, C. Alexandre Segre, Fernando Gomes, Adriano F. Ribeiro, José Carlos Nicolau & Vanda M. Yoshida

  2. University of Texas Southwestern Medical Center, Dallas, TX, USA

    James A. de Lemos

  3. Molecular Biochemistry/Biology Department, São Paulo Federal University/Paulista School of Medicine–CINTERGEN, São Paulo, Brazil

    Hugo P. Monteiro

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  1. Carlos V. Serrano Jr.
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  2. Antônio Eduardo Pesaro
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Correspondence to Carlos V. Serrano Jr..

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Serrano, C.V., Pesaro, A.E., de Lemos, J.A. et al. Native LDL-Cholesterol Mediated Monocyte Adhesion Molecule Overexpression is Blocked by Simvastatin. Cardiovasc Drugs Ther 23, 215–220 (2009). https://doi.org/10.1007/s10557-008-6159-y

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  • DOI: https://doi.org/10.1007/s10557-008-6159-y

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