title: Cardioprotective activity of placental growth factor in a rat model of acute myocardial infarction: nanoparticle-based delivery versus direct myocardial injection.
abstract: BACKGROUND
  To comparatively evaluate the cardioprotective activity of placental growth factor (PGF) delivered through direct injection and a nanoparticle-based system respectively and to study the underlying mechanisms in a rat model of acute myocardial infarction (AMI).
  
  
  METHODS
  Poly lactic-co-glycolic acid (PLGA)-based PGF-carrying nanoparticles (PGF-PLGANPs) were created. The mean size and morphology of particles were analyzed with particle size analyzer and transmission electronic microscopy (TEM). Encapsulation efficiency and sustained-release dose curve were analyzed by ELISA. Sprague-Dawley rats were randomized into four groups (n = 10). While animals in the first group were left untreated as controls, those in the other 3 groups underwent surgical induction of AMI, followed by treatment with physiological saline, PGF, and PGF-PLGANPs, respectively. Cardiac function was evaluated by transthoracic echocardiography at 4 weeks after treatment. At 6 weeks, rats were sacrificed, infarction size was analyzed with Masson trichrome staining, and protein contents of TIMP-2, MT1-MMP and MMP-2 at the infarction border were determined by immunohistochemistry and western blotting analysis.
  
  
  RESULTS
  PGF was released for at least 15 days, showing successful preparation of PGF-PLGANPs. Coronary artery ligation successfully induced AMI. Compared to physiological saline control, PGF, injected to the myocardium either as a nude molecule or in a form of nanoparticles, significantly reduced infarction size, improved cardiac function, and elevated myocardial expression of TIMP-2, MT1-MMP, and MMP-2 (P < 0.05). The effect of PGF-PLGANPs was more pronounced than that of non-encapsulated PGF (P < 0.05).
  
  
  CONCLUSIONS
  Target PGF delivery to myocardium may improve cardiac function after AMI in rats. PLGA-based nanoparticles appear to be a better approach to delivery PGF. PGF exerts its cardioprotective effect at least partially through regulating metalloproteinase-mediated myocardial tissue remodeling.
authors.forename: Zhe-Xin
authors.initials: ZX
authors.lastname: Lu
authors.forename: Li-li
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pu-Jian Rd, Shanghai 200127, People's Republic of China. dr.lianfeng@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Lian
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Wen-tian
authors.initials: WT
authors.lastname: Zhang
authors.forename: Chen-yang
authors.initials: CY
authors.lastname: Dai
authors.forename: Song
authors.initials: S
authors.lastname: Xue
authors.forename: Wei-gen
authors.initials: WG
authors.lastname: Lu
authors.forename: Hong-sheng
authors.initials: HS
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D006801:Humans; D015552:Injections, Intralesional; D019344:Lactic Acid / Q000737:chemistry*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles; D000072483:Placenta Growth Factor; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011257:Pregnancy Proteins / Q000008:administration & dosage* / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D012995:Solubility; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; C000608036:PGF protein, human; C000608038:Pgf protein, rat; D011257:Pregnancy Proteins; D011994:Recombinant Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D000072483:Placenta Growth Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D053511:Matrix Metalloproteinase 14
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