Effect of simvastatin or its combination with ezetimibe on Toll-like receptor expression and lipopolysaccharide – Induced cytokine production in monocytes of hypercholesterolemic patients
| Autor: | Alexandros D. Tselepis, Moses Elisaf, Elisavet Moutzouri, Constantinos C. Tellis, Evangelos Liberopoulos, Kleopatra Rousouli, H. J. Milionis |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Lipopolysaccharides Male Simvastatin medicine.medical_specialty Time Factors Lipopolysaccharide medicine.medical_treatment Hypercholesterolemia Interleukin-1beta Down-Regulation Ezetimibe Simvastatin Drug Combination Monocytes chemistry.chemical_compound Ezetimibe Internal medicine medicine Humans Prospective Studies Interleukin 6 Aged Greece biology Interleukin-6 business.industry Anticholesteremic Agents Toll-Like Receptors Middle Aged Flow Cytometry Toll-Like Receptor 2 Toll-Like Receptor 4 Drug Combinations TLR2 Treatment Outcome Endocrinology Cytokine chemistry biology.protein TLR4 Azetidines Cytokines Interleukin 19 Female lipids (amino acids peptides and proteins) Hydroxymethylglutaryl-CoA Reductase Inhibitors Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Atherosclerosis. 225:381-387 |
| ISSN: | 0021-9150 |
| Popis: | Toll-like receptors (TLRs) are key players in the innate immune system. Recently, a pivotal role of TLR2 and TLR4 has been recognized in atherogenesis. We investigated the effect of simvastatin monotherapy or its combination with ezetimibe on TLR2 and TLR4 membrane expression and on lipopolysaccharide (LPS)-induced interleukin-1β (IL-1β) and interleukin-6 (IL-6) production in peripheral blood monocytes of patients with primary hypercholesterolemia.This was a prospective, randomized, open-label, blinded endpoint study. After a 3-month period of lifestyle changes patients (n = 60) (mean age 55 ± 13) with LDL-cholesterol levels above those recommended by the NCEP ATP III, were randomly allocated to open-label simvastatin 40 mg (n = 30) or simvastatin/ezetimibe 10/10 mg (n = 30) daily. Both groups were similar with regard to demographics, risk factors, medications and baseline lipid values. TLR2 and TLR4 membrane expression in monocytes, LPS-induced intracellular production of IL-1β and IL-6 were assessed by flow cytometry at baseline and 3 months post-treatment in both patient groups, as well as in 30 age- and sex-matched normolipidemic controls.Hypercholesterolemic patients exhibited higher TLR2 and TLR4 membrane expression compared with controls (p0.02). LPS induced a significant increase in the intracellular levels of IL-1β and IL-6 in all groups however both patient groups exhibited significantly lower levels compared with controls. Three months of treatment with either simvastatin or its combination with ezetimibe resulted in a significant reduction of TLR2 and TLR4 expression (p0.01 compared with baseline values) with no intergroup differences. Furthermore, in both groups the post-treatment values of LPS-induced IL-1β and IL-6 production were significantly lower compared with baseline (p0.05 for all comparisons).A high simvastatin dose or the combination of a low-dose simvastatin with ezetimibe reduce to a similar extent TLR2, TLR4 membrane expression and LPS-induced IL-6 and IL-1β production in monocytes of hypercholesterolemic patients. The pathophysiological significance of these effects regarding atherosclerosis, reserves further investigation. |
| Databáze: | OpenAIRE |
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