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Open Access Research article

Cardioprotective activity of placental growth factor in a rat model of acute myocardial infarction: nanoparticle-based delivery versus direct myocardial injection

Zhe-xin Lu1, Li-li Mao2, Feng Lian1*, Jun He2*, Wen-tian Zhang1, Chen-yang Dai1, Song Xue1, Wei-gen Lu2 and Hong-sheng Zhu1

Author Affiliations

1 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

2 National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, 1111 Zhong-shan North 1 Rd, Shanghai 200437, People’s Republic of China

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BMC Cardiovascular Disorders 2014, 14:53  doi:10.1186/1471-2261-14-53

Published: 17 April 2014

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).

Conclusion

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.

Keywords:
Placental growth factor; Acute myocardial infarction; Cardiac function; Nanoparticles-mediated drug delivery; Vicious ventricular remodeling