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MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα.
Cardiovasc Diabetol. 2019 01 11; 18(1):7.CD

Abstract

BACKGROUND

Metabolic abnormalities have been implicated as a causal event in diabetic cardiomyopathy (DCM). However, the mechanisms underlying cardiac metabolic disorder in DCM were not fully understood.

RESULTS

Db/db mice, palmitate treated H9c2 cells and primary neonatal rat cardiomyocytes were employed in the current study. Microarray data analysis revealed that PGC-1β may play an important role in DCM. Downregulation of PGC-1β relieved palmitate induced cardiac metabolism shift to fatty acids use and relevant lipotoxicity in vitro. Bioinformatics coupled with biochemical validation was used to confirm that PGC-1β was one of the direct targets of miR-30c. Remarkably, overexpression of miR-30c by rAAV system improved glucose utilization, reduced excessive reactive oxygen species production and myocardial lipid accumulation, and subsequently attenuated cardiomyocyte apoptosis and cardiac dysfunction in db/db mice. Similar effects were also observed in cultured cells. More importantly, miR-30c overexpression as well as PGC-1β knockdown reduced the transcriptional activity of PPARα, and the effects of miR-30c on PPARα was almost abated by PGC-1β knockdown.

CONCLUSIONS

Our data demonstrated a protective role of miR-30c in cardiac metabolism in diabetes via targeting PGC-1β, and suggested that modulation of PGC-1β by miR-30c may provide a therapeutic approach for DCM.

Authors+Show Affiliations

Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Cardiology, China-Japan Friendship Hospital, No. 2 Yinghua Dongjie, Beijing, 100029, China.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. chenchen@tjh.tjmu.edu.cn.Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. dwwang@tjh.tjmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30635067

Citation

Yin, Zhongwei, et al. "MiR-30c/PGC-1β Protects Against Diabetic Cardiomyopathy Via PPARα." Cardiovascular Diabetology, vol. 18, no. 1, 2019, p. 7.
Yin Z, Zhao Y, He M, et al. MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα. Cardiovasc Diabetol. 2019;18(1):7.
Yin, Z., Zhao, Y., He, M., Li, H., Fan, J., Nie, X., Yan, M., Chen, C., & Wang, D. W. (2019). MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα. Cardiovascular Diabetology, 18(1), 7. https://doi.org/10.1186/s12933-019-0811-7
Yin Z, et al. MiR-30c/PGC-1β Protects Against Diabetic Cardiomyopathy Via PPARα. Cardiovasc Diabetol. 2019 01 11;18(1):7. PubMed PMID: 30635067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα. AU - Yin,Zhongwei, AU - Zhao,Yanru, AU - He,Mengying, AU - Li,Huaping, AU - Fan,Jiahui, AU - Nie,Xiang, AU - Yan,Mengwen, AU - Chen,Chen, AU - Wang,Dao Wen, Y1 - 2019/01/11/ PY - 2018/09/20/received PY - 2019/01/03/accepted PY - 2019/1/13/entrez PY - 2019/1/13/pubmed PY - 2019/4/24/medline KW - Cardiac metabolism KW - Diabetic cardiomyopathy KW - PGC-1β KW - miR-30c SP - 7 EP - 7 JF - Cardiovascular diabetology JO - Cardiovasc Diabetol VL - 18 IS - 1 N2 - BACKGROUND: Metabolic abnormalities have been implicated as a causal event in diabetic cardiomyopathy (DCM). However, the mechanisms underlying cardiac metabolic disorder in DCM were not fully understood. RESULTS: Db/db mice, palmitate treated H9c2 cells and primary neonatal rat cardiomyocytes were employed in the current study. Microarray data analysis revealed that PGC-1β may play an important role in DCM. Downregulation of PGC-1β relieved palmitate induced cardiac metabolism shift to fatty acids use and relevant lipotoxicity in vitro. Bioinformatics coupled with biochemical validation was used to confirm that PGC-1β was one of the direct targets of miR-30c. Remarkably, overexpression of miR-30c by rAAV system improved glucose utilization, reduced excessive reactive oxygen species production and myocardial lipid accumulation, and subsequently attenuated cardiomyocyte apoptosis and cardiac dysfunction in db/db mice. Similar effects were also observed in cultured cells. More importantly, miR-30c overexpression as well as PGC-1β knockdown reduced the transcriptional activity of PPARα, and the effects of miR-30c on PPARα was almost abated by PGC-1β knockdown. CONCLUSIONS: Our data demonstrated a protective role of miR-30c in cardiac metabolism in diabetes via targeting PGC-1β, and suggested that modulation of PGC-1β by miR-30c may provide a therapeutic approach for DCM. SN - 1475-2840 UR - https://www.unboundmedicine.com/medline/citation/30635067/MiR_30c/PGC_1β_protects_against_diabetic_cardiomyopathy_via_PPARα_ L2 - https://cardiab.biomedcentral.com/articles/10.1186/s12933-019-0811-7 DB - PRIME DP - Unbound Medicine ER -