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Overexpression of miR-22 attenuates oxidative stress injury in diabetic cardiomyopathy via Sirt 1.
Cardiovasc Ther. 2018 Apr; 36(2)CT

Abstract

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 C57BL/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 (GRP78, 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.

Authors+Show Affiliations

Department of Cardiology, Dongyang People's Hospital, Dongyang, China.Department of Cardiology, Wuhan People's Hospital, Wuhan, China.Department of Cardiology, Wuhan People's Hospital, Wuhan, China.Key Laboratory of Biochemistry, Wuhan People's Hospital, Wuhan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29288528

Citation

Tang, Qinghui, et al. "Overexpression of miR-22 Attenuates Oxidative Stress Injury in Diabetic Cardiomyopathy Via Sirt 1." Cardiovascular Therapeutics, vol. 36, no. 2, 2018.
Tang Q, Len Q, Liu Z, et al. Overexpression of miR-22 attenuates oxidative stress injury in diabetic cardiomyopathy via Sirt 1. Cardiovasc Ther. 2018;36(2).
Tang, Q., Len, Q., Liu, Z., & Wang, W. (2018). Overexpression of miR-22 attenuates oxidative stress injury in diabetic cardiomyopathy via Sirt 1. Cardiovascular Therapeutics, 36(2). https://doi.org/10.1111/1755-5922.12318
Tang Q, et al. Overexpression of miR-22 Attenuates Oxidative Stress Injury in Diabetic Cardiomyopathy Via Sirt 1. Cardiovasc Ther. 2018;36(2) PubMed PMID: 29288528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Overexpression of miR-22 attenuates oxidative stress injury in diabetic cardiomyopathy via Sirt 1. AU - Tang,Qinghui, AU - Len,Qiang, AU - Liu,Zheng, AU - Wang,WeiDong, Y1 - 2018/02/14/ PY - 2017/08/01/received PY - 2017/11/27/revised PY - 2017/12/21/accepted PY - 2017/12/31/pubmed PY - 2018/9/7/medline PY - 2017/12/31/entrez KW - Sirt 1 KW - diabetic cardiomyopathy KW - high glucose KW - miR-22 KW - oxidative stress JF - Cardiovascular therapeutics JO - Cardiovasc Ther VL - 36 IS - 2 N2 - 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 C57BL/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 (GRP78, 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. SN - 1755-5922 UR - https://www.unboundmedicine.com/medline/citation/29288528/Overexpression_of_miR_22_attenuates_oxidative_stress_injury_in_diabetic_cardiomyopathy_via_Sirt_1_ L2 - https://doi.org/10.1111/1755-5922.12318 DB - PRIME DP - Unbound Medicine ER -