Tags

Type your tag names separated by a space and hit enter

HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia.
J Am Coll Cardiol. 1997 Nov 01; 30(5):1212-7.JACC

Abstract

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.

Authors+Show Affiliations

Institut für Prophylaxe der Kreislaufkrankheiten, Ludwig-Maximilians-Universität, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9350917

Citation

Weber, C, et al. "HMG-CoA Reductase Inhibitors Decrease CD11b Expression and CD11b-dependent Adhesion of Monocytes to Endothelium and Reduce Increased Adhesiveness of Monocytes Isolated From Patients With Hypercholesterolemia." Journal of the American College of Cardiology, vol. 30, no. 5, 1997, pp. 1212-7.
Weber C, Erl W, Weber KS, et al. HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. J Am Coll Cardiol. 1997;30(5):1212-7.
Weber, C., Erl, W., Weber, K. S., & Weber, P. C. (1997). HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. Journal of the American College of Cardiology, 30(5), 1212-7.
Weber C, et al. HMG-CoA Reductase Inhibitors Decrease CD11b Expression and CD11b-dependent Adhesion of Monocytes to Endothelium and Reduce Increased Adhesiveness of Monocytes Isolated From Patients With Hypercholesterolemia. J Am Coll Cardiol. 1997 Nov 1;30(5):1212-7. PubMed PMID: 9350917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from patients with hypercholesterolemia. AU - Weber,C, AU - Erl,W, AU - Weber,K S, AU - Weber,P C, PY - 1997/11/14/pubmed PY - 1997/11/14/medline PY - 1997/11/14/entrez SP - 1212 EP - 7 JF - Journal of the American College of Cardiology JO - J. Am. Coll. Cardiol. VL - 30 IS - 5 N2 - 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. SN - 0735-1097 UR - https://www.unboundmedicine.com/medline/citation/9350917/HMG_CoA_reductase_inhibitors_decrease_CD11b_expression_and_CD11b_dependent_adhesion_of_monocytes_to_endothelium_and_reduce_increased_adhesiveness_of_monocytes_isolated_from_patients_with_hypercholesterolemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(97)00324-0 DB - PRIME DP - Unbound Medicine ER -