title: Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice.
abstract: OBJECTIVE
  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
  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.affiliation: Institutes of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu Province, China, 215123.
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.forename: Minghui
authors.initials: M
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Ni
authors.forename: Grace
authors.initials: G
authors.lastname: Wang
authors.forename: Ruizhen
authors.initials: R
authors.lastname: Chen
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
authors.forename: Guo-Chang
authors.initials: GC
authors.lastname: Fan
authors.forename: James C
authors.initials: JC
authors.lastname: Lacefield
authors.forename: Tianqing
authors.initials: T
authors.lastname: Peng
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D058065:Diabetic Cardiomyopathies / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C569389:MIRN195a microRNA, mouse; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse; D053148:Caspase 3; D056564:Sirtuin 1