STUDY ON THE MECHANISM OF CARDIAC HYPERTROPHY INDUCED BY TESTOSTERONE THROUGH MTORC2 IN OVARIECTOMIZED FEMALE SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Listen

Translate article

Objective: The estrogen level of postmenopausal women decreased sharply, while the androgen level did not decrease significantly, which was characterized by the inversion of estrogen / androgen ratio. Therefore, it could be observed that relative excess androgen in the circulation of postmenopausal women, which may be one of the reasons for the increase of cardiovascular disease in postmenopausal women. In this study, the model of postmenopausal hypertension was established by bilateral ovariectomy in spontaneously hypertensive rats (SHR), and the specific mechanism of testosterone-induced myocardial hypertrophy in ovariectomized SHR was explored. Design and method: Twenty-four SHR were randomly divided into three groups: sham operation group (Sham group, n = 8), bilateral ovariectomized group (OVX group, n = 8) and testosterone propionate intervention group (OVX+T group, 2.85mg/kg Weekly, im for4 weeks, n = 8). The systolic blood pressure, diastolic blood pressure and heart rate of SHR were monitored and recorded twice a week. Western Blot was used to detect the protein expression of mTOR, p-mTOR, mTORC2 and its subunits Rictor and p-Rictor. Moreover, the expression of autophagy-related proteins LC3 and P62/SQSTM1 and Mitofusin2 (MFN2) and Dynamin related protein 1 (DRP1) in cardiac myocytes was observed. Results: 1. Testosterone could activate the expression of mTORC2 in myocardial tissue: testosterone could activate the expression of mTORC2 and the Rictor of mTORC2 in ovariectomized SHR(Figure 1). 2. Testosterone could inhibit cardiomyocyte autophagy: there was no significant difference in the expression of autophagy-related proteins LC3 and P62/SQSTM1 between Sham and OVX groups, while testosterone could decrease the expression of LC3 protein and increase the expression of P62/SQSTM1 protein in OVX+T group (Figure 2). 3. Testosterone could activate the mitochondrial cleavage of cardiomyocytes: the expression of DRP1 was increased in OVX+T group (Figure 3). Conclusions: In bilateral ovariectomized SHR, testosterone may inhibit cardiomyocyte autophagy by activating the expression of mTORC2, which leads to cardiac hypertrophy in SHR. And in cardiomyocyte mitochondria, testosterone can promote mitochondrial cleavage.