Abstract
BackgroundTo 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).MethodsPoly 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.ResultsPGF 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).ConclusionTarget 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.
Highlights
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)
This study aimed to investigate the therapeutic efficacy of PGF-PLGANPs-bearing nanoparticles against acute myocardial infarction (AMI) in comparison with direct administration of PGF as well as the mechanistic role of Tissue inhibitors of metalloproteinases (TIMPs)-2, MT1-matrix metalloproteinases (MMPs) and MMP-2-regulated cardiac remodeling in PGF-mediated cardioprotection in a rat model
In vitro release kinetics of PGF-PLGANPs Shown in Figure 2 are concentrations of PGF released from PGF-PLGANPs at different time points during the 15-day experiment as determined by enzyme-linked immunosorbent assay (ELISA)
Summary
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). Paracrine factors derived from stem cells have been demonstrated to be capable of improving cardiac function after myocardial infarction (MI) and are becoming a hot topic of myocardial regeneration research [1,2]. One of these factors is placental growth factor (PGF). Through activating MMP-2, MT1-MMP may aggravate the degradation and loss of ECM [6] It remains unclear whether PGF may exerts its beneficial effect against ischemic myocardial injury through regulating MMP-dependent ECM degradation in the myocardium
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