Open AccessOverexpression of miR‐22 attenuates oxidative stress injury in diabetic cardiomyopathy via Sirt 1
Author(s) -
Tang Qinghui,
Len Qiang,
Liu Zheng,
Wang WeiDong
Publication year - 2018
Publication title -
cardiovascular therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 46
eISSN - 1755-5922
pISSN - 1755-5914
DOI - 10.1111/1755-5922.12318
Subject(s) - oxidative stress , diabetic cardiomyopathy , medicine , malondialdehyde , apoptosis , viability assay , streptozotocin , chop , endocrinology , diabetes mellitus , reactive oxygen species , cardiomyopathy , heart failure , biology , microbiology and biotechnology , biochemistry , lymphoma
Summary Background/Aims Oxidative stress injury is believed to be important in diabetic cardiomyopathy. Recent evidence indicates that miR‐22 plays an important role in various cardiovascular diseases, but the protective role of miR‐22 in diabetic cardiomyopathy remains undetermined. Methods Diabetes was induced in male C57 BL /6 mice by intraperitoneal injection with streptozotocin combined with a high‐fat diet, and miR‐22 was overexpressed following transfection with adeno‐associated virus. Cardiac function was assessed by echocardiography and a cardiac catheter system. In vitro study, H9c2 cells were treated with normal or high glucose ( HG ), and cell viability or apoptosis was detected using the Cell Counting Kit‐8 ( CCK ‐8) assay and flow cytometry, respectively. Reactive oxygen species, malondialdehyde, and superoxide dismutase were also detected in diabetic mice and H9c2 cells. The expression level of miR‐22 was detected by real‐time PCR . The protein expression of Sirt 1, oxidative stress injury‐related proteins ( GRP 78, CHOP , ATF 3), and apoptosis‐related proteins Bax/Bcl‐2, cl‐casp‐9/casp‐9, and cl‐casp‐3/casp‐3 were determined by Western blotting analysis. Results HG ‐induced oxidative stress injury and apoptosis were observed in H9c2 cells, which were ameliorated by miR‐22. Cardiac dysfunction and severely altered heart structure were also observed in diabetic mice and were dramatically reversed by overexpression of miR‐22. The expression of Sirt 1 decreased significantly in diabetic mice and HG ‐treated H9c2 cells. Overexpression of miR‐22 restored the level of Sirt 1. Bioinformatics analysis predicted that Sirt 1 was a potential target gene of miR‐22. Luciferase reporter assay verified that miR‐22 promoted Sirt 1 expression by direct binding to the Sirt 1 3′untranslated repeats. Upregulation of Sirt 1 could improve cell viability and attenuate oxidative stress injury and apoptosis in the HG ‐treated H9c2 cells, similar to the effect of miR‐22. However, the protective effects of miR‐22 against HG ‐induced oxidative stress injury and apoptosis were abrogated by knockdown of Sirt 1. Conclusions Overexpression of miR‐22 can attenuate oxidative stress injury in diabetic cardiomyopathy by upregulation of Sirt 1 in vivo and in vitro.