Role and molecular mechanism of Notch signaling pathway in the process of myocardial fibrosis mediated by polycystic ovary syndrome

  AIM  To investigate the role and mechanism of Notch signaling pathway in myocardial fibrosis induced by polycystic ovary syndrome.

  METHODS  Rats were given letrozole by gavage to establish PCOS model. The experiment was divided into: negative control group, letrozoleintervention group 200 μg/d, Notch1 agonist Jagged1 treatment group, Notch1 agonist Jagged1+ letrozole intervention group (200 μg/d). The changes of serum levels of estradiol (E2) and follicle-stimulating growth hormone (FSH) in each group were observed after successful modeling on 21 d. HE staining was used to detect the morphological changes of ovary in each group. Changes of molecules related to Notch signaling pathway in heart tissues of each group were detected by Western blot.

  RESULTS  PCOS model was successfully established by gavage of letrozole. Compared with the control group, TG, TC, HDL and LDL in serum were significantly increased in the PCOS model group (P<0.05). Heart coefficient of PCOS model group was significantly higher than that of the control group (P<0.05). In the PCOS group, the myocardial cells showed fibrotic changes, collagen increased, and molecules related to Notch signaling pathway were inhibited. The agonist intervention of Notch signaling pathway had no effect on the serum content and inhibited letrozole-induced increased collagen expression in rat cardiomyocytes.

  CONCLUSION  Notch signaling pathway can inhibit the process of myocardial fibrosis mediated by PCOS and has a protective effect on the occurrence of cardiovascular diseases caused by PCOS.