title: Angiogenesis in the infarcted myocardium.
abstract: CONCLUSIONS
  Proangiogenic therapy appeared a promising strategy for the treatment of patients with acute myocardial infarction (MI), as de novo formation of microvessels, has the potential to salvage ischemic myocardium at early stages after MI, and is also essential to prevent the transition to heart failure through the control of cardiomyocyte hypertrophy and contractility.
  
  
  BACKGROUND
  Exciting preclinical studies evaluating proangiogenic therapies for MI have prompted the initiation of numerous clinical trials based on protein or gene transfer delivery of growth factors and administration of stem/progenitor cells, mainly from bone marrow origin. Nonetheless, these clinical trials showed mixed results in patients with acute MI.
  
  
  RESULTS
  Even though methodological caveats, such as way of delivery for angiogenic growth factors (e.g., protein vs. gene transfer) and stem/progenitor cells or isolation/culture procedure for regenerative cells might partially explain the failure of such trials, it appears that delivery of a single growth factor or cell type does not support angiogenesis sufficiently to promote cardiac repair.
  
  
  CONCLUSIONS
  Optimization of proangiogenic therapies might include stimulation of both angiogenesis and vessel maturation and/or the use of additional sources of stem/progenitor cells, such as cardiac progenitor cells. Experimental unraveling of the mechanisms of angiogenesis, vessel maturation, and endothelial cell/cardiomyocyte cross talk in the ischemic heart, analysis of emerging pathways, as well as a better understanding of how cardiovascular risk factors impact endogenous and therapeutically stimulated angiogenesis, would undoubtedly pave the way for the development of novel and hopefully efficient angiogenesis targeting therapeutics for the treatment of acute MI.
authors.affiliation: Paris Cardiovascular Research Center, INSERM UMR-S 970, Paris Descartes University, Paris, France.
authors.forename: Clement
authors.initials: C
authors.lastname: Cochain
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Silvestre
mesh_terms: D053687:Adult Stem Cells / Q000637:transplantation; D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology; D002196:Capillaries / Q000502:physiology; D002450:Cell Communication; D002986:Clinical Trials as Topic; D003326:Coronary Circulation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000502:physiology; D015316:Genetic Therapy; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use; D051379:Mice; D035683:MicroRNAs / Q000627:therapeutic use; D008833:Microcirculation; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000601:surgery; D032383:Myocytes, Cardiac / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology; D033581:Stem Cell Transplantation / Q000379:methods; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D043925:Angiogenesis Inducing Agents; D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1; D036341:Intercellular Signaling Peptides and Proteins; D035683:MicroRNAs; D019001:Nitric Oxide Synthase; D000099162:Endothelial PAS Domain-Containing Protein 1