Summary:
The in vitro effect of a statin and an estrogen on oxidation of human LDL was investigated for the first time, comparing the monosubstances fluvastatin and 17β-estradiol as well as the effect of the combination. Fluvastatin significantly delayed the onset of LDL oxidation (controls = 90 min) by 23 min at 1 μM, by 110 min and by 221 min at 5 and 10 μM, respectively. 17β-estradiol significantly impeded the onset by 70 min at 1 μM and by more than 300 min at 5 and 10 μM. The combination of 1 μM 17β-estradiol with 1, 5 and 10 μM fluvastatin showed an additive antioxidative effect; the onset was delayed by 100 min, by 167 min, and by more than 300 min, respectively. It can be concluded that treatment of postmenopausal women with fluvastatin and 17β-estradiol may have not only beneficial effects on lipid disorders but may also elicit a direct potent anti-atherosclerotic action on the vasculature.
Key words:
Fluvastatin - 17β-estradiol - LDL-oxidation
References
-
1
Grodstein F, Stampfer M J, Colditz G A, Willett W C, Manson J E, Joffe M, Rosner B, Fuches C, Hankinson S E, Hunter D J, Hennekens C H, Speizer F E.
Postmenopausal hormone therapy and mortality.
N Engl J Med.
336
1769-1775
1997;
-
2
Hebert P R, Gaziano J M, Chan K S, Hennekens C H.
Cholesterol lowering with statin drugs, risk of stroke, and total mortality.
JAMA.
278
313-312
1997;
-
3
Leonhardt W, Kurktschiev T, Meissner D, Lattke P, Abletshauser C, Weidinger G, Jaross W, Hanefeld M.
Effects of fluvastatin therapy on lipids, antioxidants, oxidation of low density lipoproteins and trace metals.
Eur J Clin Pharmacol.
53
65-69
1997;
-
4
Mendelsson M E, Karas R H.
The protective effects of estrogen on the cardiovascular system.
New Engl J Med.
340
1801-1811
1999;
-
5
Sack M N, Rader D J. Cannon RO 3rd
.
Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women.
Lancet.
343
269-270
1994;
-
6
Steinberg D.
Oxidative modification of LDL and atherogenesis.
Circulation.
95
1062-1071
1997;
-
7
Vaughan C J, Murphy M B, Buckley B M.
Statins do more than just lower cholesterol.
Lancet.
348
1079-1082
1996;
1 * p < 0.05; ** p < 0.01 compared to control value
Priv.-Doz. Dr. med. Dipl. Chem. Dr. rer. nat. A. O. Mueck
Section of Gynecological Endocrinology and Menopause
Department of Obstetrics and Gynecology
Schleichstraße 4
D-72076 Tuebingen
Fax: + 49-70 71-29 48 01