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01.08.2015 | Article

Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice

verfasst von: Dong Zheng, Jian Ma, Yong Yu, Minghui Li, Rui Ni, Grace Wang, Ruizhen Chen, Jianmin Li, Guo-Chang Fan, James C. Lacefield, Tianqing Peng

Erschienen in: Diabetologia | Ausgabe 8/2015

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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.

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Titel: Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice
verfasst von: Dong Zheng
Jian Ma
Yong Yu
Minghui Li
Rui Ni
Grace Wang
Ruizhen Chen
Jianmin Li
Guo-Chang Fan
James C. Lacefield
Tianqing Peng
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 8/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-015-3622-8

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