title: Thrombopoietin improved ventricular function and regulated remodeling genes in a rat model of myocardial infarction.
abstract: BACKGROUND
  Thrombopoietin (TPO) protects against heart damages by doxorubicin-induced cardiomyopathy in animal models. We aimed to investigate the therapeutic efficacy of TPO for treatment of myocardial infarction (MI) in a rat model and explored the mechanisms in terms of the genome-wide transcriptional profile, TPO downstream protein signals, and bone marrow endothelial progenitor cells (EPCs).
  
  
  METHODS
  Sprague-Dawley rats were divided into 3 groups: Sham-operated, MI (permanent ligation of the left coronary artery) and MI+TPO. Three doses of TPO were administered weekly for 2 weeks, and outcomes were assessed at 4 or 8 weeks post-injury.
  
  
  CONCLUSIONS
  TPO treatment significantly improved left ventricular function, hemodynamic parameters, myocardium morphology, neovascularization and infarct size. MI damage upregulated a large cohort of gene expressions in the infarct border zone, including those functioned in cytoskeleton organization, vascular and matrix remodeling, muscle development, cell cycling and ion transport. TPO treatment significantly reversed these modulations. While phosphorylation of janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT) was modified in MI animals, TPO treatment regulated phosphorylation of STAT3 and extracellular signal-regulated kinases (ERK), and bone morphogenetic protein 1 (BMP1) protein level. TPO also increased EPC colonies in the bone marrow of MI animals. Our data showed that TPO alleviated damages of heart tissues from MI insults, possibly mediated by multi-factorial mechanisms including suppression of over-reacted ventricular remodeling, regulation of TPO downstream signals and mobilization of endothelial progenitor cells. TPO could be developed for treatment of cardiac damages.
authors: Department of Paediatrics, The Chinese University of Hong Kong, Hong Kong.
authors: Kathy Yuen Yee
authors: KY
authors: Chan
authors: Ligang
authors: L
authors: Zhou
authors: Ping
authors: P
authors: Xiang
authors: Karen
authors: K
authors: Li
authors: Pak Cheung
authors: PC
authors: Ng
authors: Chi Chiu
authors: CC
authors: Wang
authors: Ming
authors: M
authors: Li
authors: Nga Hin
authors: NH
authors: Pong
authors: Liu
authors: L
authors: Tu
authors: Haiyan
authors: H
authors: Deng
authors: Carrie Ka Lai
authors: CK
authors: Kong
authors: Rita Yn Tz
authors: RY
authors: Sung
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013926:Thrombopoietin / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology*
chemical_list: D013926:Thrombopoietin