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Daidzein (DZ) and genistein are both estrogenic isoflavones. The function of genistein attenuating cardiac hypertrophy and remodeling was widely reported and some studies have shown us more protective effects of DZ than genistein in many different diseases. But the effects and underlying mechanisms of DZ in cardiac remodeling are still unclear. The purpose of this study is to estimate the effects of DZ in cardiac remodeling and try to explore the underlying mechanisms.
In our study, C57BL/6 mice (male, 8 to 10 weeks, 23.5-27.5g weight) were subjected to aortic banding (AB) operation or Sham as control. After operation the mice were gavaged with DZ (100mg/kg) or Placebo for 8 weeks. After that, we estimate the role of DZ in cardiac remodeling by echocardiography, pressure-volume (PV) detection, heart weighing, histological analysis, mRNA expression level analysis. And to find a possible mechanism, the protein levels of possible signaling pathways were detected by Western Blot.
As results, DZ suppressed the increase of heart weight/body weight (HW/BW) and heart weight/tibial length (HW/TL) after AB. In echocardiography, DZ attenuated the enlargement of left ventricle end-diastolic diameter (LVEDD) and left ventricle end-systolic diameter (LVESD), and protect the decline of ejection fraction (EF) and fractional shorten (FS). In the histological analysis, HE and PSR stain demonstrated that DZ group reduces the degrees of cardiomyocytes hypertrophy and interstitial fibrosis. In the detection of RT-PCR, the mRNA levels of hypertrophic markers, like ANP, BNP and β-MHC, in DZ group were raised much slightly after AB, and fibrotic markers, like CTGF, TGF-β2, Collagen Ia and Collagen III, have the same tendencies. In the mechanism research, the expression levels of BAX, Bcl-2, cleaved-caspase3 and cleaved-caspase9 have been detected, and DZ inhibits the activation of apoptosis via mitochondrial pathway.
DZ presents a protective effect on pressure overload-induced cardiac remodeling. And in this procedure DZ suppressed apoptosis through mitochondrial pathway. Probably DZ is a potential therapeutic drug for cardiac remodeling.