title: Intramyocardial sustained delivery of placental growth factor using nanoparticles as a vehicle for delivery in the rat infarct model.
abstract: BACKGROUND
  Acute myocardial ischemia results in scar formation with ventricular dilatation and eventually heart failure. Placental growth factor (PlGF) is reported to stimulate angiogenesis and improve cardiac function. In this study, it was hypothesized that intramyocardial injection of PlGF contained in nanoparticles can be released at the site of action for an extended time period as a sustained slow-release protective mechanism that accelerates myocardial recovery in a rat model of ischemic cardiomyopathy.
  
  
  METHODS
  PlGF-loaded chitosan-alginate nanoparticles were injected into an acute myocardial infarction model in rats (n = 10 per group). Transthoracic echocardiography was performed at different time intervals. Enzyme-linked immunosorbent assay was used to measure the serum cytokines levels at 8 weeks. Hearts were stained with Masson's trichrome for scar area analysis. Immunofluorostaining was performed to evaluate the extent of myocardial angiogenesis at the infarction border. PlGF enzyme-linked immunosorbent assay was used to measure the in vitro release kinetics of PlGF-loaded nanoparticles.
  
  
  RESULTS
  At 8 weeks after coronary ligation, hearts that were treated with PlGF-loaded chitosan-alginate nanoparticles had significant increases in left-ventricular function (P < 0.01), vascular density (P < 0.01), and in the serum level of the anti-inflammatory cytokine interleukin-10 (P < 0.05). There was significant decrease in scar area formation (P < 0.05) and in serum levels of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-6 (P < 0.01). In vitro PlGF-release kinetic studies showed a sustained release of PlGF from the particles over a 120-hour period.
  
  
  CONCLUSIONS
  The use of nanoparticles as a vehicle for PlGF delivery, as opposed to the direct injection of the growth factor after acute myocardial infarction, can provide sustained slow-release PlGF therapy, enhancing the positive effects of the growth factor in the setting of acute myocardial ischemia.
authors: Divisions of Cardiac Surgery and Surgical Research, McGill University Health Center, McGill University, Montreal, Quebec, Canada.
authors: Ziyad Mohammed
authors: ZM
authors: Binsalamah
authors: Arghya
authors: A
authors: Paul
authors: Afshan Afsar
authors: AA
authors: Khan
authors: Satya
authors: S
authors: Prakash
authors: Dominique
authors: D
authors: Shum-Tim
mesh_terms: D000464:Alginates / Q000737:chemistry; D000704:Analysis of Variance; D000818:Animals; D048271:Chitosan / Q000737:chemistry; D016207:Cytokines / Q000097:blood; D004562:Electrocardiography; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007150:Immunohistochemistry; D009203:Myocardial Infarction / Q000188:drug therapy*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D011917:Rats, Inbred Lew; D013318:Stroke Volume / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000464:Alginates; D016207:Cytokines; D006603:Hexuronic Acids; C000608038:Pgf protein, rat; D014677:Pharmaceutical Vehicles; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D020723:Glucuronic Acid; D048271:Chitosan