title: Depressed expression of angiogenic growth factors in the subacute phase of myocardial ischemia: a mechanism behind the remodeling plateau?
abstract: OBJECTIVE
  To investigate whether, in the subacute phase of acute myocardial infarction, in the peri-infarcted area the expressions of the vascular endothelial growth factor (VEGF-A) and angiopoietin (Ang) ligand receptors are depressed, and whether overexpression of these angiogens counteracts a downregulation of myocardial function.
  
  
  METHODS
  Acute myocardial infarction was induced by left anterior descending artery ligation and overexpression through injection of human VEGF-A165 and Ang-1 plasmids. The capillary and arteriolar densities, Akt-1 phosphorylation and citrate synthase activity were measured concurrent with the expression of VEGF-A, VEGFR1 and R2, Ang-1, Ang-2 and Tie-2.
  
  
  RESULTS
  One day after AMI, VEGR-2 was unchanged but all other measured factors in the two families were upregulated. After day 2, the Ang-2 expression increased but other measured factors decreased. After gene transfer, the vascular supply, Akt phosphorylation and citrate synthase activity were higher in the peri-infarcted area, where also the endogenous angiogenic growth factor expressions were increased.
  
  
  CONCLUSIONS
  A rapid decrease in angiogenic stimulating factors occurs in the subacute phase of AMI and is related to a progressive decrease in myocardial contraction. A negative consequence of such a circuit is a successive reduction in the vascular supply and contractility in areas with reduced perfusion. These negative adaptations can be counteracted by angiogen overexpression.
authors.affiliation: Department of Medicine, Division of Cardiology, Section of Integrative Physiology, Karolinska University Hospital, Karolinska Institutet, 141 86 Stockholm, Sweden. Anwar.J.Siddiqui@ki.se
authors.forename: Anwar Jewel
authors.initials: AJ
authors.lastname: Siddiqui
authors.forename: Helene
authors.initials: H
authors.lastname: Fischer
authors.forename: Ulrika
authors.initials: U
authors.lastname: Widegren
authors.forename: Karl-Henrik
authors.initials: KH
authors.lastname: Grinnemo
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Hao
authors.forename: Agneta
authors.initials: A
authors.lastname: Månsson-Broberg
authors.forename: Christer
authors.initials: C
authors.lastname: Sylvén
authors.forename: Thomas
authors.initials: T
authors.lastname: Gustafsson
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000096:biosynthesis / Q000235:genetics; D042702:Angiopoietin-2 / Q000378:metabolism; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: C467630:ANGPT1 protein, human; D042501:Angiogenic Proteins; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D002950:Citrate (si)-Synthase; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt