title: Placental growth factor 2--A potential therapeutic strategy for chronic myocardial ischemia.
abstract: OBJECTIVE
  We investigated whether sustained infusion of recombinant human placental growth factor-2 (rhPlGF-2) improves myocardial perfusion and left ventricular (LV) function in a porcine model of ischemic cardiomyopathy (ICM).
  
  
  METHODS
  We induced myocardial ischemia using a flow-limiting stent in the LAD. Four weeks later, we randomized pigs with confirmed myocardial dysfunction to blinded rhPlGF-2 administration (PlGF2, 15 μg/kg/day, 14 days) or PBS (CON). At 8 weeks, we measured hemodynamics, contractile function and regional perfusion at rest and during stress using MRI and microspheres. We evaluated neovascularization post mortem.
  
  
  RESULTS
  RhPlGF-2 administration increased PlGF serum levels more than 63-fold (83 3 ± 361 versus 11 ± 5 pg/ml CON, P<0.05) without adverse effects. After 4weeks, rhPlGF-2 significantly enhanced perfusion in the ischemic region at rest (0.83 ± 0.32 versus 0.58 ± 0.21 ml/min/g CON, P<0.05) and during hyperemia (1.50 ± 0.50 versus 1.02 ± 0.46 ml/min/g CON, P<0.05). Consequently, regional contractile function in rhPlGF-2-treated pigs improved at rest (37 ± 15% versus 23 ± 9% CON, P<0.05) and during high dose dobutamine stress (53 ± 31% versus 27 ± 16% CON, P<0.05). Enhanced perfusion translated into a greater improvement in LV ejection fraction and in preload-recruitable stroke work in rhPlGF-2-treated animals than in CON (52 ± 11 versus 41 ± 9%, and 76 ± 24 versus 41 ± 21 mmHg, respectively, P<0.05 for both), which was associated with significantly greater vascular density in the ischemic region.
  
  
  CONCLUSIONS
  In chronic ICM, systemic rhPlGF-2 administration significantly enhances regional myocardial perfusion, contractile function at rest and during stress, and induces a prominent recovery of global cardiac function. PlGF-2 protein infusion is safe and may represent a promising therapy in chronic ICM.
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Ming
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Claus
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Nina
authors.initials: N
authors.lastname: Vanden Driessche
authors.affiliation: Thrombogenics NV., Leuven, Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Reyns
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Pokreisz
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Gillijns
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Caluwe
authors.affiliation: Department of Imaging and Pathology, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaert
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium.
authors.forename: Desire
authors.initials: D
authors.lastname: Collen
authors.affiliation: Department of Cardiovascular Sciences, KU Leuven, University Hospital Leuven, Leuven, Belgium. Electronic address: Stefan.janssens@med.kuleuven.be.
authors.forename: Stefan
authors.initials: S
authors.lastname: Janssens
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D008297:Male; D008565:Membrane Proteins / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D017410:Practice Guidelines as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use*; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D008565:Membrane Proteins; C098069:PIGF protein, human; D011994:Recombinant Proteins
keywords: Angiogenesis; Chronic myocardial ischemia; Growth factors; Placental growth factor 2