involvement of microrna-133 and -29 in cardiac disturbances in diabetic ovariectomized rats
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abstract
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 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. materials and methods: 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. results: 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). conclusion: 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.
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Journal title:
iranian journal of basic medical sciencesجلد ۱۹، شماره ۱۱، صفحات ۱۱۷۷-۱۱۸۵
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