Involvement of microRNA-133 and -29 in cardiac disturbances in diabetic ovariectomized rats

• Published in: Iranian journal of basic medical sciences Vol. 19; no. 11; pp. 1177 - 1185
• Main Authors: Habibi, Parisa, Alihemmati, Alireza, Nasirzadeh, Mohammadreza, Yousefi, Hadi, Habibi, Mohammadrasoul, Ahmadiasl, Nasser
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01.11.2016
• Subjects: Cardiac fibrosis; Diabetes; Menopause; MicroRNA; Original; Cardiac fibrosis; MicroRNA; Diabetes; Menopause
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/ijbms.2016.7817

Menopause and diabetes obviously increase the risk of cardiovascular disease in women. The aims of the present study were to evaluate the effects of ovariectomy in type 2 diabetes on the histology and expression of miRNA-29, miRNA-133, IGF-1 and Bcl-2 genes and Bcl-2 protein and caspase 3 activity in the hearts of female rats. Forty Female Wistar rats were divided into four groups: control, sham, ovariectomized (OVX), and ovariectomized with type 2 diabetes (OVX.D). After the 8-week experiment, the histological evaluation of the heart tissue was performed using H&E staining and PAS analysis, and cardiac expression of miRNA-29, miRNA-133, IGF-1, and Bcl-2 were evaluated using real-time PCR, and Bcl-2 protein and caspase 3 activity were evaluated using Western blot and ELISA. Ovariectomy significantly decreased miRNA-29, miRNA-133, IGF-1, and BCL-2 expression and Bcl-2 protein and increased caspase 3 activity in the heart compared to sham animals group (P<0.05). Type 2 diabetes in ovariectomized rats markedly decreased expression of miRNA-29, miRNA-133, IGF-1, BCL-2 genes, and Bcl-2 protein, and increased caspase 3 activity and reduced collagen and fibroblast tissue and glycogen granule deposition in relation to OVX group (P<0.05). Our findings suggest that type 2 diabetes and menopause synergically could enhance the cardiac fibrosis through dysregulation of miRNA-29, miRNA-133, IGF-1, and Bcl-2 genes expression and Bcl-2 protein and upregulation of caspase 3 activity.