phytoestrogens and Cardiomegaly

Cardiac hypertrophy is a common finding in human patients with inborn errors of long-chain fatty acid oxidation. Mice with either very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD-/-) or long-chain acyl-coenzyme A dehydrogenase deficiency (LCAD-/-) develop cardiac hypertrophy. Cardiac hypertrophy, initially measured using heart/body weight ratios, was manifested most severely in LCAD-/- male mice. VLCAD-/- mice, as a group, showed a mild increase in normalized cardiac mass (8.8% hypertrophy compared with all wild-type (WT) mice). In contrast, LCAD-/- mice as a group showed more severe cardiac hypertrophy (32.2% increase compared with all WT mice). On the basis of a clear male predilection, we analyzed the role of dietary plant estrogenic compounds commonly found in mouse diets because of soy or alfalfa components providing natural phytoestrogens or isoflavones in cardioprotection of LCAD-/- mice. Male LCAD-/- mice fed an isoflavone-free test diet had more severe cardiac hypertrophy (58.1% hypertrophy compared with WT mice fed the same diet). There were no significant differences in the female groups fed any of the diets. Echocardiography measurement performed on male LCAD-deficient mice fed a standard diet at the age of approximately 3 months confirmed the substantial cardiac hypertrophy in these mice compared with WT controls. Left ventricular (LV) wall thickness of the interventricular septum and posterior wall was remarkably increased in LCAD-/- mice compared with that of WT controls. Accordingly, the calculated LV mass after normalization to body weight was increased by about 40% in the LCAD-/- mice compared with WT mice. In summary, we found that metabolic cardiomyopathy, expressed as hypertrophy, developed in mice because of either VLCAD deficiency or LCAD deficiency; however, LCAD deficiency was the most profound and seemed to be attenuated either by endogenous estrogen (in females) or by phytoestrogens present in the diet as isoflavones (in males).

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Animals; Body Weight; Cardiomegaly; Diet; Disease Models, Animal; Echocardiography; Female; Isoflavones; Male; Mice; Mice, Knockout; Myocardium; Organ Size; Phytoestrogens

Intact female rats fed a high-phytoestrogen diet are protected against adverse left ventricular (LV) remodeling induced by chronic volume overload. We hypothesized that both phytoestrogens and ovarian hormones, particularly estrogen, are necessary for this dietary-induced cardioprotection. To test this hypothesis, eight groups of female rats were studied; rats were fed either a high-phytoestrogen (+phyto) or phytoestrogen-free diet. Groups included sham-operated rats, intact rats with fistula (Fist), ovariectomized rats with fistula (Fist-OX), and Fist-OX rats treated with estrogen (EST). Myocardial function and remodeling were assessed after 8 wk of volume overload using a blood-perfused isolated heart apparatus. Fist-OX rats developed significant ventricular dilatation and increased compliance vs. intact Fist rats, which were associated with a significant decrease in contractility. Estrogen treatment prevented pulmonary edema and attenuated LV hypertrophy and dilatation but did not maintain contractility. However, dietary phytoestrogens completely prevented LV dilatation in both the Fist+phyto and Fist-OX+EST+phyto groups but had no effect on LV remodeling in the Fist-OX+phyto group. Contractility was significantly greater in the estrogen-treated rats fed the phytoestrogen diet than in those treated with estrogen alone. Dietary phytoestrogens did not affect LV or uterine mass, serum estrogen, LV estrogen receptor expression, or cardiac function in sham animals. These data indicate that estrogen is not solely responsible for the cardioprotection exhibited by intact females and that phytoestrogens can work synergistically with ovarian hormones to attenuate ventricular remodeling induced by chronic volume overload in female rats.

Topics: Animals; Aorta, Abdominal; Arteriovenous Shunt, Surgical; Cardiac Output; Cardiomegaly; Chronic Disease; Diet; Disease Models, Animal; Estrogen Replacement Therapy; Estrogens; Female; Heart Failure; Myocardial Contraction; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley; Time Factors; Venae Cavae; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling