Effects of raloxifene treatment on the phenotype of blood monocytes.
Raloxifene (RLX), a selective oestrogen receptor modulator, has oestrogen-agonist effects on bone, lipoproteins, and homocysteine and oestrogen-antagonist activity in the breast and uterus, positioning it as a potential drug for long-term prevention of coronary heart disease in postmenopausal women. To further evaluate its influence on cardiovascular risk factors, we studied the effects of 60 mg/day RLX on serum lipid levels, inflammatory (high-sensitivity C-reactive protein, and coagulation (fibrinogen) markers, monocytes, and fibrinolysis in 15 healthy postmenopausal women. Markers were measured at baseline, after 1 month without treatment, and after 3 months of treatment. Fibrinolysis was evaluated using the euglobulin clot lysis time (ECLT) determined with a new semiautomatic optical method. Monocyte phenotype was determined by measurement of the expression of the antigens CD14, HLA-DR, and CD62-L using flow cytometry. After 3 months of RLX treatment, we observed a decrease in total cholesterol (p = 0.002), in low-density lipoprotein cholesterol (p <0.001), and in lipoprotein A (p = 0.01). Fibrinogen (p = 0.002) decreased significantly, and high-sensitivity C-reactive protein had a tendency to decrease, but this did not reach statistical significance (p = 0.06). RLX treatment had no effect on ECLT (p = 0.223) or on white blood cell, lymphocyte, and total monocyte counts (p = 0.313). Monocyte expression of HLA-DR, CD14, and CD62-L was not modified by the treatment. In conclusion, we confirm that RLX has beneficial short-term effects on levels of lipids and inflammatory markers, with no effect on fibrinolysis or monocyte phenotype.
Boudjeltia
Karim Zouaoui
KZ
Experimental Medicine Laboratory, ULB 222 Unit, Université Libre de Bruxelles, Intercommunale de santé publique du pays de Charleroi, CHU de Charleroi, Hôpital André Vésale, 6110 Montigny-Le-Tilleul, Belgium. karim.zouaoui@chu-charleroi.be
Durez
Patrick
P
Oberweis
Didier
D
Guillaume
Michel
M
Remacle
Claude
C
Cauchie
Philippe
P
Vanhaeverbeek
Michel
M
Brohée
Dany
D
Ducobu
Jean
J
Gregoir
Catherine
C
D000368:Aged; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D019041:L-Selectin / Q000096:biosynthesis / Q000097:blood; D007958:Leukocyte Count; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D008076:Cholesterol, HDL; D016207:Cytokines; D018950:Lipopolysaccharide Receptors; D017270:Lipoprotein(a); D020845:Selective Estrogen Receptor Modulators; D019041:L-Selectin; D020849:Raloxifene Hydrochloride; D002784:Cholesterol