Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin

Carlos V. Serrano, Antônio Eduardo Pesaro, James A de Lemos, Fabiana Rached, C. Alexandre Segre, Fernando Gomes, Adriano F. Ribeiro, José Carlos Nicolau, Vanda M. Yoshida, Hugo P. Monteiro

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)215-220
Number of pages6
JournalCardiovascular Drugs and Therapy
Volume23
Issue number3
DOIs
StatePublished - Jun 2009

Keywords

  • Adhesion molecules
  • Atherosclerosis
  • Inflammation
  • Monocyte
  • Native LDL-cholesterol
  • Simvastatin

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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    Serrano, C. V., Pesaro, A. E., de Lemos, J. A., Rached, F., Segre, C. A., Gomes, F., Ribeiro, A. F., Nicolau, J. C., Yoshida, V. M., & Monteiro, H. P. (2009). Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin. Cardiovascular Drugs and Therapy, 23(3), 215-220. https://doi.org/10.1007/s10557-008-6159-y