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

Monocytes are recruited as the principal inflammatory cells into the athero sclerotic lesion. In a previous study we demonstrated that a low HDL-choles terol and the apo E4 allele are associated with an increased proportion of blood monocytes that are characterized by a high expression of Fc gamma-RII Ia (CD16), a dim expression of the lipopolysaccharide (LPS) receptor (CD14) and a high expression of beta(1)- and beta(2)-integrins (Rothe et al. Arte rioscler Thromb Vase Cell Biol 1996;16:1437-1447). In this study, 79 hyperc holesterolemic patients were treated either with the HMG CoA reductase inhi bitor fluvastatin in combination with diet or with placebo and diet in a do uble-blind and randomized multicenter study, and monitored for the potentia l effects on the phenotype of peripheral blood monocytes. At baseline, in t he whole group of hypercholesterolemic patients the population size of thes e more mature monocytes (CD14(dim)CD16(+)) was positively correlated to tri glyceride (P=0.003) and total serum cholesterol levels (P = 0.012) confirmi ng our previous study. Fluvastatin treatment for 52 weeks was associated wi th a 24.2% reduction in LDL-cholesterol (P < 0.001) as well as a 40.7% decr ease 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 m ore differentiated CD14(dim)CD16(+) monocytes further confirmed this modifi cation of the phenotype of peripheral blood monocytes. The positive pre-stu dy correlation of the CD14(dim)CD16(+) monocyte subset to the serum cholest erol concentration, but inverse changes of both parameters under fluvastati n therapy, in conclusion indicate that fluvastatin exerts an as yet unchara cterized immunomodulatory effect on either monocyte maturation and differen tiation, or extravasation which may also depend on the endothelial phenotyp e that is independent of the change in serum lipids. (C) 1999 Elsevier Scie nce Ireland Ltd. All rights reserved.