title: MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis.
abstract: OBJECTIVE
  To determine the role of microRNA 21(miR-21) on left ventricular remodeling of rat heart with ischemia-reperfusion (I/R) injury and to investigate the underlying mechanism of miR-21 mediated myocardium protection.
  
  
  METHODS
  Rats were randomly divided into three groups: an I/R model group with Ad-GFP (Ad-GFP group), an I/R model group with Ad-miR-21 (Ad-miR-21 group) and a sham-surgery group. Changes in hemodynamic parameters were recorded at 1 week after I/R. Histological diagnosis was achieved by hematoxylin and eosin (H&E). Left ventricular (LV) dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells were measured. Primary cultures of neonatal rat cardiac ventricular myocytes were performed and cell ischemic injury was induced by hypoxia in a serum- and glucose-free medium, and reoxygenation (H/R). MiR-21 inhibitor and pre-miR-21 were respectively added to the culture medium for the miR-21 knockdown and for the miR-21 up-regulation. qRT-PCR was used to determine the miR-21 levels in cultured cells. Flow cytometry was performed to examine the cell apoptosis.
  
  
  RESULTS
  In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group. At 1 week after I/R, the Ad-miR-21 significantly improved LVSP, LV +dp/dt(max), LV - dp/dt(min), and decreased heart rate (HR) and LVEDP compared with the Ad-GFP group. Compared with the Ad-GFP, the cell apoptotic rate significantly decreased in the Ad-miR-21 group. The miR-21 inhibitor exacerbated cardiac myocyte apoptosis and the pre-miR-21 decreased hypoxia/reoxygenation- induced cardiac myocyte apoptosis.
  
  
  CONCLUSIONS
  Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury.
authors.affiliation: Department of Emergency, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Qin
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Yu
authors.forename: Hua
authors.initials: H
authors.lastname: Dong
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Bian
authors.forename: Xuan
authors.initials: X
authors.lastname: Guo
authors.forename: Shimin
authors.initials: S
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D006439:Hemodynamics / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D020257:Ventricular Remodeling / Q000235:genetics / Q000502:physiology*
chemical_list: D035683:MicroRNAs; D003094:Collagen