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Although favorable effects of estrogen replacement ther-apy on atherosclerosis have been recognized, the bene-fit versus risk of estrogen replacement on overall cardio- vascular health remains controversial. The main adverse effect jeopardizing the clinical usage of estrogen is the increased risk of breast and endometrial cancer. Zear-alenone (ZEN) is a universal endogenous hormone pos-sessing estrogen-like effects and facilitating plant growth. α-Zearalanol (α-ZAL), a new phytoestrogen, is a reduc-tive product of ZEN. Our preliminary evidence suggested that α-ZAL is anti-atherosclerotic. The aim of this study was to examine the effect of α-ZAL on atherosclerotic formation and serum lipid profile. Adult female nulli-parous rabbits were ovariectomized or sham-operated and fed a high-cholesterol diet with different doses of α-ZAL or 17β-estradiol for 12 wk. The aortic intimal atherosclerotic plaque was significantly larger in the cho-lesterol-fed group compared to control and sham groups. α-ZAL and 17β-estradiol treatments significantly reduced plaque formation and improved serum profile of lipid (TC, TG, HDL-C, and LDL-C) and lipoprotein (ApoAl and ApoB). Both α-ZAL and 17β-estradiol reconciled ovariectomy-induced uterine atrophy, although α-ZAL was significantly less potent than 17β-estradiol in stimulating uterine growth. Our findings indicate that the phytoestrogen α-ZAL has an important anti-atherogenic property, analogous to that of estrogen. [ABSTRACT FROM AUTHOR]

Estrogen replacement therapy (ERT) is one of the most challenging issues women and their physicians have to face. Clinical and epidemiological studies have provided conflicting data regarding the cardiovascular ben-efit versus risk in women using ERT. Although ERT may improve several risk factors of coronary heart disease such as favorable changes in lipid profile, an associated increased incidence of uterine and breast tumors has jeopardized the clinical use of ERT. We reported here that the phytoestrogen α-zearalanol is effective against atherosclerotic development without overt growth-pro-moting effects in the uterus compared to estrogen. These results suggest clinical potential of this phytoestrogen as a "safe estrogen" with less risk of tumorogenesis. [ABSTRACT FROM AUTHOR]

While the benefit and risk of estrogen replacement therapy for cardiovascular disease remains controversial, women frequently choose alternatives to estrogen such as phytoestrogen for treatment of menopause even though medical indications for estrogens may exist. Phytoestrogens also possess distinct advantages over mammalian estrogens because their usage in men without feminizing side effects. Nevertheless, the cardiac contractile function of estrogen or phytoestrogen has not been clearly elucidated. The aim of the present study was to compare the effect of 17β estradiol (E2) and phytoestrogen α-zearalanol (ZAL) on cardiac mechanical function and intracellular Ca2+ transients at cellular levels. Isolated ventricular myocytes from adult female rats were stimulated to contract at 0.5 Hz. Contractile properties were evaluated using an IonOptix MyoCam® system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), and maximal velocity of shortening/relengthening (± dL/dt). Intracellular Ca2+ properties were evaluated as fura-2 fluorescent intensity change (ΔFFI) and intracellular Ca2+ decay rate. Acute administration of E2 -9–10-5 M) elicited a concentration-dependent increase in PS and ΔFFI, with maximal augmentation of approx 35% and 25%, respectively. TPS, TR90, ± dL/dt, resting intracellular Ca2+ level, and intracellular Ca2+ decay were unaffected by E2. None of the mechanical or intracellular Ca2+ indices tested was affected by phytoestrogen ZAL (10-9–10-5 M). Our results revealed a direct cardiac stimulatory action from E2 but not from phytoestrogen ZAL on ventricular contraction, likely mediated through enhanced intracellular Ca2+ release. [ABSTRACT FROM AUTHOR]