Effects of resveratrol and estradiol on expression of cardiac hypertrophy markers in ovariectomized mice carrying knockout aryl hydrocarbon receptor

Nguyen, Ba Tiep , Dr. Seidlová-Wuttke, Dana , Prof. Dr. Wuttke, Wolfgang , Prof. Dr. Jarry, Hubertus. University of Goettingen Endocrinology, Robert-Koch, 37075 Goettingen, Germany.

Background. Aryl hydrocarbon receptor (AhR) plays an important role in normal development and homeostasis. AhR gene knockout (KO) resulted in heart hypertrophy but changes in expression of molecular markers of this phenotype are controversial. In addition, estradiol (E2) contributes cardiac effects via binding to estrogen receptors that have a crosstalk with AhR suggesting changes in regulation on hypertrophy markers of E2 in AhRKO heart. Since resveratrol (Res), a phytoestrogen, has cardiovascular protective properties, it may have AhR-correlated estrogenic effects on cardiac gene expression that were identified in this study.

Methods. Female AhRKO mice (2 months of age) were ovariectomized (ovx), given soy free (SF) food or diet containing E2 (0.015mg/animal/day) or Res (2.68mg/animal/day). A group of same number (n=6) of wild type ovx mice fed with SF food was included. The mice were sacrificed after 3 months. Cross section areas (CSAs) of cardiomyocytes were measured on H&E stained slides from mid transverse sectional rings of left ventricle (LV) using analysis®3.0 software. mRNA levels in LV were determined by real time RT-PCR. The differences were considered significant at P<0.05 using Student’ t-test.

Results. AhRKO resulted in heart hypertrophy, i.e. increased heart weights (HW), LV weights, HW/body weight (BW) and LV/BW. Only E2 exaggerated hypertrophy levels in ovx AhRKO mice together with increased cardiomyocyte CSAs. Surprisingly, mRNA levels of both alpha and beta MHC were decreased in hypertrophic hearts of ovx AhRKO mice; both E2 and Res reversed the reduction. Expression of ANF was down regulated by Res, not by E2.

Conclusions. Heart hypertrophy due to AhRKO might not associate with increase in expression of molecular markers. E2 augmented AhRKO-induced heart hypertrophy. Differences in expression of hypertrophy markers under E2 and Res treatment might contribute to cardiac protective effect of resveratrol.

Supported by EUGeneHeart Project.