title: Increased expression of integrin-linked kinase improves cardiac function and decreases mortality in dilated cardiomyopathy model of rats.
abstract: OBJECTIVE
  Integrin-linked kinase (ILK) is a multifunctional kinase linking the extracellular matrix to intracellular signaling pathways, whose activation in the heart gives rise to a number of functional consequences. The aim of this study is to demonstrate the therapeutic and survival benefit of cardiac ILK overexpression in a rat model of dilated cardiomyopathy.
  
  
  RESULTS
  The dilated cardiomyopathy model was generated in rats by intraperitoneal administration of six equal doses of doxorubicin over a 2 week period. Five weeks after the first injection, echocardiographic analysis demonstrated impaired cardiac function and, at that point, recombinant adenoviral vector harboring ILK cDNA or vehicle was injected into the myocardium, and the rats re-studied 4 weeks later. Compared with vehicle injection, ILK treatment ameliorated inflammatory cell infiltration and cardiomyocyte degeneration, as well as left ventricular dilation and dysfunction. ILK treatment was also associated with a reduction in apoptosis and an increase in proliferation of cardiomyocytes, as well as decreased oxidative stress and autophagic vacuole accumulation. Importantly, mortality was lower in rats following ILK treatment than in those following vehicle injection. In cultured neonatal rat cardiomyocytes, we also found that ILK overexpression protected against doxorubicin-induced apoptosis, giving rise to an increase in their proliferation.
  
  
  CONCLUSIONS
  These data demonstrate for the first time that ILK gene therapy improves cardiac function and survival in a model of dilated cardiomyopathy, and this may be mediated through suppression of inflammation, prevention of ventricular remodeling, inhibition of cardiomyocyte apoptosis and autophagy, and stimulation of cardiomyocyte proliferation.
authors.affiliation: Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
authors.forename: Lin
authors.initials: L
authors.lastname: Ling
authors.forename: Liang
authors.initials: L
authors.lastname: Ding
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Ye
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D006321:Heart / Q000502:physiology*; D007249:Inflammation / Q000188:drug therapy; D009026:Mortality; D032383:Myocytes, Cardiac / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D051381:Rats; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000187:drug effects; D000099200:Scaffold Protein ILK
chemical_list: D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK