A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment in hypercholesterolemic patients with coronary heart disease

Rothe, Gregor and Herr, Alexandra S. and Stoehr, Josef and Abletshauser, Claudia and Weidinger, Gottfried and Schmitz, Gerd (1999) A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment in hypercholesterolemic patients with coronary heart disease. ATHEROSCLEROSIS, 144 (1). pp. 251-261. ISSN 0021-9150, 1879-1484

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Abstract

Monocytes are recruited as the principal inflammatory cells into the atherosclerotic lesion. In a previous study we demonstrated that a low HDL-cholesterol and the apo E4 allele are associated with an increased proportion of blood monocytes that are characterized by a high expression of Fc gamma-RIIIa (CD16), a dim expression of the lipopolysaccharide (LPS) receptor (CD14) and a high expression of beta(1)- and beta(2)-integrins (Rothe et al. Arterioscler Thromb Vase Cell Biol 1996;16:1437-1447). In this study, 79 hypercholesterolemic patients were treated either with the HMG CoA reductase inhibitor fluvastatin in combination with diet or with placebo and diet in a double-blind and randomized multicenter study, and monitored for the potential effects on the phenotype of peripheral blood monocytes. At baseline, in the whole group of hypercholesterolemic patients the population size of these more mature monocytes (CD14(dim)CD16(+)) was positively correlated to triglyceride (P=0.003) and total serum cholesterol levels (P = 0.012) confirming our previous study. Fluvastatin treatment for 52 weeks was associated with a 24.2% reduction in LDL-cholesterol (P < 0.001) as well as a 40.7% decrease in the expression density of CD14 on all monocytes (P = 0.027). A 24.5% decrease (P < 0.001) of the population of less differentiated CD14(bright)CD16(-) monocytes and an 83.1% increase (P = 0.029) of the population of more differentiated CD14(dim)CD16(+) monocytes further confirmed this modification of the phenotype of peripheral blood monocytes. The positive pre-study correlation of the CD14(dim)CD16(+) monocyte subset to the serum cholesterol concentration, but inverse changes of both parameters under fluvastatin therapy, in conclusion indicate that fluvastatin exerts an as yet uncharacterized immunomodulatory effect on either monocyte maturation and differentiation, or extravasation which may also depend on the endothelial phenotype that is independent of the change in serum lipids. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: COLONY-STIMULATING FACTOR; COA REDUCTASE INHIBITORS; NECROSIS-FACTOR-ALPHA; INTRACELLULAR-TRANSPORT; DETERGENT INSOLUBILITY; CARDIOVASCULAR-DISEASE; ALKALINE-PHOSPHATASE; ANCHORED PROTEIN; PERIPHERAL-BLOOD; HUMAN MONOCYTES; monocyte subpopulations; mononuclear phagocyte differentiation; atherosclerosis; hypercholesterolemia; fluvastatin
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 19 Oct 2022 12:28
Last Modified: 19 Oct 2022 12:28
URI: https://pred.uni-regensburg.de/id/eprint/48258

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