Parisa Habibi - Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran
Alireza Alihemmati - Department of Histology & Embryology, Tabriz University of Medical Sciences, Tabriz, Iran
Mohammadreza Nasirzadeh - Department of Physiology, Tabriz Branch, Islamic Azad University, Tabriz, Iran
Hadi Yousefi - Department of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran
Mohammadrasoul Habibi - Tabriz University of Medical Sciences, Tabriz, Iran
Nasser Ahmadiasl - Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Objective(s): 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 ۲ diabetes on the histology and expression of miRNA-۲۹, miRNA-۱۳۳, IGF-۱ and Bcl-۲ genes and Bcl-۲ protein and caspase ۳ activity in the hearts of female rats. Materials and Methods: Forty Female Wistar rats were divided into four groups: control, sham, ovariectomized (OVX), and ovariectomized with type ۲ diabetes (OVX.D). After the ۸-week experiment, the histological evaluation of the heart tissue was performed using H&E staining and PAS analysis, and cardiac expression of miRNA-۲۹, miRNA-۱۳۳, IGF-۱, and Bcl-۲ were evaluated using real-time PCR, and Bcl-۲ protein and caspase ۳ activity were evaluated using Western blot and ELISA. Results: Ovariectomy significantly decreased miRNA-۲۹, miRNA-۱۳۳, IGF-۱, and BCL-۲ expression and Bcl-۲ protein and increased caspase ۳ activity in the heart compared to sham animals group (P<۰.۰۵). Type ۲ diabetes in ovariectomized rats markedly decreased expression of miRNA-۲۹, miRNA-۱۳۳, IGF-۱, BCL-۲ genes, and Bcl-۲ protein, and increased caspase ۳ activity and reduced collagen and fibroblast tissue and glycogen granule deposition in relation to OVX group (P<۰.۰۵). Conclusion: Our findings suggest that type ۲ diabetes and menopause synergically could enhance the cardiac fibrosis through dysregulation of miRNA-۲۹, miRNA-۱۳۳, IGF-۱, and Bcl-۲ genes expression and Bcl-۲ protein and upregulation of caspase ۳ activity.

Cardiac fibrosis, Diabetes, Menopause, MicroRNA