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 Citations (Scopus)

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

Fingerprint

Simvastatin
LDL Cholesterol
Monocytes
Therapeutics
Coronary Artery Disease
Lipids
L-Selectin
Hypercholesterolemia
Atherosclerosis
Suspensions
oxidized low density lipoprotein

Keywords

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

ASJC Scopus subject areas

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

Cite this

Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin. / Serrano, Carlos V.; Pesaro, Antônio Eduardo; de Lemos, James A; Rached, Fabiana; Segre, C. Alexandre; Gomes, Fernando; Ribeiro, Adriano F.; Nicolau, José Carlos; Yoshida, Vanda M.; Monteiro, Hugo P.

In: Cardiovascular Drugs and Therapy, Vol. 23, No. 3, 06.2009, p. 215-220.

Research output: Contribution to journalArticle

Serrano, CV, Pesaro, AE, de Lemos, JA, Rached, F, Segre, CA, Gomes, F, Ribeiro, AF, Nicolau, JC, Yoshida, VM & Monteiro, HP 2009, 'Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin', Cardiovascular Drugs and Therapy, vol. 23, no. 3, pp. 215-220. https://doi.org/10.1007/s10557-008-6159-y
Serrano, Carlos V. ; Pesaro, Antônio Eduardo ; de Lemos, James A ; Rached, Fabiana ; Segre, C. Alexandre ; Gomes, Fernando ; Ribeiro, Adriano F. ; Nicolau, José Carlos ; Yoshida, Vanda M. ; Monteiro, Hugo P. / Native LDL-cholesterol mediated monocyte adhesion molecule overexpression is blocked by simvastatin. In: Cardiovascular Drugs and Therapy. 2009 ; Vol. 23, No. 3. pp. 215-220.
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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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AU - Pesaro, Antônio Eduardo

AU - de Lemos, James A

AU - Rached, Fabiana

AU - Segre, C. Alexandre

AU - Gomes, Fernando

AU - Ribeiro, Adriano F.

AU - Nicolau, José Carlos

AU - Yoshida, Vanda M.

AU - Monteiro, Hugo P.

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N2 - 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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KW - Atherosclerosis

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KW - Monocyte

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