Related Experiment Video
Updated: Jul 21, 2026
Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and
1Institut für Prophylaxe der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Munich, Germany.
Insights
Statins reduce monocyte CD11b expression and adhesion to endothelium. This mechanism may explain their clinical benefit in coronary heart disease (CHD), independent of cholesterol reduction.
Area of Science:
- Cardiovascular Research
- Immunology
- Pharmacology
Background:
- HMG-CoA reductase inhibitors (statins) improve survival in coronary heart disease (CHD).
- Statins modulate monocyte functions, potentially by reducing adhesion to endothelium, a key process in atherogenesis.
Purpose of the Study:
- To investigate the effect of HMG-CoA reductase inhibitors on CD11b expression and monocyte adhesion.
- To determine if these effects occur in vitro and in hypercholesterolemic patients.
Main Methods:
- Flow cytometry and adhesion assays were used to assess CD11b expression and monocyte adhesion.
- Monocytes were treated with lovastatin in vitro and ex vivo from hypercholesterolemic patients before and after statin treatment.
Main Results:
- In vitro lovastatin treatment dose-dependently reduced monocyte CD11b expression and adhesion.
- Mevalonate, but not LDL, reversed lovastatin's effects, indicating the importance of cholesterol precursors.
- Statin treatment in hypercholesterolemic patients significantly reduced monocyte adhesion to endothelium.
Conclusions:
- Reduced CD11b expression and inhibited CD11b-dependent monocyte adhesion contribute to the clinical benefits of statins in CHD.
- These effects appear independent of cholesterol-lowering actions.
Objectives:
This study sought to determine whether inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase affect CD11b expression and adhesiveness of monocytes in vitro and after treatment of patients with hypercholesterolemia.
Background:
HMG-CoA reductase inhibitors improve survival of patients with coronary heart disease (CHD) and prevent CHD in hypercholesterolemic men. Because these drugs have been shown to modulate monocyte functions, they may act by reducing monocyte adhesion to endothelium, which is crucial in atherogenesis.
Methods:
Isolated human blood monocytes were subjected to flow cytometric detection of CD11b and adhesion assays on fixed human endothelial cells after treatment with lovastatin in vitro or ex vivo before and after treatment of hypercholesterolemic patients with HMG-CoA reductase inhibitors.
Results:
The integrin heterodimer CD11b/CD18 expressed on monocytes interacts with intercellular adhesion molecule-1 on endothelium and is involved in monocyte adhesion to endothelium. Treatment of monocytes with lovastatin in vitro slightly and dose dependently reduced surface expression of CD11b on monocytes. Moreover, lovastatin inhibited CD11b-dependent adhesiveness to fixed endothelium of unstimulated monocytes or monocytes stimulated with monocyte chemotactic protein 1. Coincubation with mevalonate, but not with low density lipoprotein (LDL), reversed the effects of lovastatin, suggesting that early cholesterol precursors, but not cholesterol, are crucial for adhesiveness of CD11b. In hypercholesterolemic patients, adhesion of isolated monocytes to endothelium ex vivo was dramatically increased over values in healthy control subjects. Treatment of these patients with the HMG-CoA reductase inhibitors lovastatin or simvastatin (20 to 40 mg/day) for 6 weeks slightly decreased total and LDL cholesterol plasma levels and monocyte CD11b surface expression but resulted in a significant reduction of monocyte adhesion to endothelium (p < 0.01, n = 7).
Conclusions:
The reduction of CD11b expression and inhibition of CD11b-dependent monocyte adhesion to endothelium may crucially contribute to the clinical benefit of HMG-CoA reductase inhibitors in CHD, independent of cholesterol-lowering effects.
Related Concept Videos
01:38Receptor-mediated Endocytosis
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:29Pharmacogenomics: Identification of New Drug Targets
01:26Coronary Artery Disease IV: Preventive Measures
01:26Atherosclerosis III: Management