title: The impairment of ILK related angiogenesis involved in cardiac maladaptation after infarction.
abstract: BACKGROUND
  Integrin linked kinase (ILK), as an important component of mechanical stretch sensor, can initiate cellular signaling response in the heart when cardiac preload increases. Previous work demonstrated increased ILK expression could induce angiogenesis to improved heart function after MI. However the patholo-physiological role of ILK in cardiac remodeling after MI is not clear.
  
  
  RESULTS
  Hearts were induced to cardiac remodeling by infarction and studied in Sprague-Dawley rats. Until 4 weeks after infarction, ILK expression was increased in non-ischemic tissue in parallel with myocytes hypertrophy and compensatory cardiac function. 8 weeks later, when decompensation of heart function occurred, ILK level returned to baseline. Followed ILK alternation, vascular endothelial growth factor (VEGF) expression and phosphorylation of endothelial nitric oxide synthase (eNOS) was significantly decreased 8 weeks after MI. Histology study also showed significantly microvessel decreased and myocytes loss 8 weeks paralleled with ILK down-regulation. While ILK expression was maintained by gene delivery, tissue angiogenesis and cardiac function was preserved during cardiac remodeling.
  
  
  CONCLUSIONS
  Temporally up-regulation of ILK level in non-ischemic myocytes by increased external load is associated with beneficial angiogenesis to maintain infarction-induced cardiac hypertrophy. When ILK expression returns to normal, this cardiac adaptive response for infarction is weaken. Understanding the ILK related mechanism of cardiac maladaptation leads to a new strategy for treatment of heart failure after infarction.
authors.affiliation: Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Wen
authors.initials: W
authors.lastname: Lu
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.forename: Qin
authors.initials: Q
authors.lastname: Dai
authors.forename: Bin
authors.initials: B
authors.lastname: Zong
authors.forename: Lin
authors.initials: L
authors.lastname: Ling
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004452:Echocardiography; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D006321:Heart / Q000503:physiopathology*; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000503:physiopathology; D009203:Myocardial Infarction / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling; D000099200:Scaffold Protein ILK
chemical_list: D052250:Nitric Oxide Synthase Type III; D017346:Protein Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D000099200:Scaffold Protein ILK; C496316:Nos3 protein, rat