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Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice.
Diabetologia. 2015 Aug; 58(8):1949-58.D

Abstract

AIMS/HYPOTHESIS

MicroRNAs (miRs) have been suggested as potential therapeutic targets for heart diseases. Inhibition of miR-195 prevents apoptosis in cardiomyocytes stimulated with palmitate and transgenic overexpression of miR-195 induces cardiac hypertrophy and heart failure. We investigated whether silencing of miR-195 reduces diabetic cardiomyopathy in a mouse model of streptozotocin (STZ)-induced type 1 diabetes.

METHODS

Type 1 diabetes was induced in C57BL/6 mice (male, 2 months old) by injections of STZ.

RESULTS

MiR-195 expression was increased and levels of its target proteins (B cell leukaemia/lymphoma 2 and sirtuin 1) were decreased in STZ-induced type 1 and db/db type 2 diabetic mouse hearts. Systemically delivering an anti-miR-195 construct knocked down miR-195 expression in the heart, reduced caspase-3 activity, decreased oxidative stress, attenuated myocardial hypertrophy and improved myocardial function in STZ-induced mice with a concurrent upregulation of B cell leukaemia/lymphoma 2 and sirtuin 1. Diabetes reduced myocardial capillary density and decreased maximal coronary blood flow in mice. Knockdown of miR-195 increased myocardial capillary density and improved maximal coronary blood flow in diabetic mice. Upregulation of miR-195 sufficiently induced apoptosis in cardiomyocytes and attenuated the angiogenesis of cardiac endothelial cells in vitro. Furthermore, inhibition of miR-195 prevented apoptosis in cardiac endothelial cells in response to NEFA, an important feature of diabetes.

CONCLUSIONS/INTERPRETATION

Therapeutic silencing of miR-195 reduces myocardial hypertrophy and improves coronary blood flow and myocardial function in diabetes, at least in part by reducing oxidative damage, inhibiting apoptosis and promoting angiogenesis. Thus, miR-195 may represent an alternative therapeutic target for diabetic heart diseases.

Authors+Show Affiliations

Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China, 215123.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25994075

Citation

Zheng, Dong, et al. "Silencing of miR-195 Reduces Diabetic Cardiomyopathy in C57BL/6 Mice." Diabetologia, vol. 58, no. 8, 2015, pp. 1949-58.
Zheng D, Ma J, Yu Y, et al. Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia. 2015;58(8):1949-58.
Zheng, D., Ma, J., Yu, Y., Li, M., Ni, R., Wang, G., Chen, R., Li, J., Fan, G. C., Lacefield, J. C., & Peng, T. (2015). Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia, 58(8), 1949-58. https://doi.org/10.1007/s00125-015-3622-8
Zheng D, et al. Silencing of miR-195 Reduces Diabetic Cardiomyopathy in C57BL/6 Mice. Diabetologia. 2015;58(8):1949-58. PubMed PMID: 25994075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. AU - Zheng,Dong, AU - Ma,Jian, AU - Yu,Yong, AU - Li,Minghui, AU - Ni,Rui, AU - Wang,Grace, AU - Chen,Ruizhen, AU - Li,Jianmin, AU - Fan,Guo-Chang, AU - Lacefield,James C, AU - Peng,Tianqing, Y1 - 2015/05/21/ PY - 2014/11/05/received PY - 2015/04/14/accepted PY - 2015/5/22/entrez PY - 2015/5/23/pubmed PY - 2016/4/14/medline SP - 1949 EP - 58 JF - Diabetologia JO - Diabetologia VL - 58 IS - 8 N2 - AIMS/HYPOTHESIS: MicroRNAs (miRs) have been suggested as potential therapeutic targets for heart diseases. Inhibition of miR-195 prevents apoptosis in cardiomyocytes stimulated with palmitate and transgenic overexpression of miR-195 induces cardiac hypertrophy and heart failure. We investigated whether silencing of miR-195 reduces diabetic cardiomyopathy in a mouse model of streptozotocin (STZ)-induced type 1 diabetes. METHODS: Type 1 diabetes was induced in C57BL/6 mice (male, 2 months old) by injections of STZ. RESULTS: MiR-195 expression was increased and levels of its target proteins (B cell leukaemia/lymphoma 2 and sirtuin 1) were decreased in STZ-induced type 1 and db/db type 2 diabetic mouse hearts. Systemically delivering an anti-miR-195 construct knocked down miR-195 expression in the heart, reduced caspase-3 activity, decreased oxidative stress, attenuated myocardial hypertrophy and improved myocardial function in STZ-induced mice with a concurrent upregulation of B cell leukaemia/lymphoma 2 and sirtuin 1. Diabetes reduced myocardial capillary density and decreased maximal coronary blood flow in mice. Knockdown of miR-195 increased myocardial capillary density and improved maximal coronary blood flow in diabetic mice. Upregulation of miR-195 sufficiently induced apoptosis in cardiomyocytes and attenuated the angiogenesis of cardiac endothelial cells in vitro. Furthermore, inhibition of miR-195 prevented apoptosis in cardiac endothelial cells in response to NEFA, an important feature of diabetes. CONCLUSIONS/INTERPRETATION: Therapeutic silencing of miR-195 reduces myocardial hypertrophy and improves coronary blood flow and myocardial function in diabetes, at least in part by reducing oxidative damage, inhibiting apoptosis and promoting angiogenesis. Thus, miR-195 may represent an alternative therapeutic target for diabetic heart diseases. SN - 1432-0428 UR - https://www.unboundmedicine.com/medline/citation/25994075/Silencing_of_miR_195_reduces_diabetic_cardiomyopathy_in_C57BL/6_mice_ L2 - https://doi.org/10.1007/s00125-015-3622-8 DB - PRIME DP - Unbound Medicine ER -