title: VEGF attenuates development from cardiac hypertrophy to heart failure after aortic stenosis through mitochondrial mediated apoptosis and cardiomyocyte proliferation.
abstract: BACKGROUND
  Aortic stenosis (AS) affects 3 percent of persons older than 65 years and leads to greater morbidity and mortality than other cardiac valve diseases. Surgery with aortic valve replacement (AVR) for severe symptomatic AS is currently the only treatment option. Unfortunately, in patients with poor ventricular function, the mortality and long-term outcome is unsatisfied, and only a minority of these patients could bear surgery. Our previous studies demonstrated that vascular endothelial growth factor (VEGF) protects cardiac function in myocardial infarction model through classic VEGF-PI3k-Akt and unclear mitochondrial anti-apoptosis pathways; promoting cardiomyocyte (CM) proliferation as well. The present study was designed to test whether pre-operative treatment with VEGF improves AS-induced cardiac dysfunction, to be better suitable for AVR, and its potential mechanism.
  
  
  METHODS
  Adult male mice were subjected to AS or sham operation. Two weeks later, adenoviral VEGF (Ad-VEGF), enhanced green fluorescence protein (Ad-EGFP, as a parallel control) or saline was injected into left ventricle free wall. Two weeks after delivery, all mice were measured by echocardiography and harvested for further detection.
  
  
  RESULTS
  AS for four weeks caused cardiac hypertrophy and left ventricular dysfunction. VEGF treatment increased capillary density, protected mitochondrial function, reduced CMs apoptosis, promoted CMs proliferation and eventually preserved cardiac function.
  
  
  CONCLUSIONS
  Our findings indicate that VEGF could repair AS-induced transition from compensatory cardiac hypertrophy to heart failure.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P R China.
authors.forename: Xiao H
authors.initials: XH
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.forename: Hai L
authors.initials: HL
authors.lastname: Cao
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Yi J
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001024:Aortic Valve Stenosis / Q000188:drug therapy* / Q000601:surgery; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D005822:Genetic Vectors; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011300:Preoperative Care; D011897:Random Allocation; D042442:Vascular Endothelial Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D042442:Vascular Endothelial Growth Factors