The online version of this article (doi:10.1186/1471-2261-14-53) contains supplementary material, which is available to authorized users.
An erratum to this article can be found at http://dx.doi.org/10.1186/s12872-015-0019-z.
A retraction note to this article can be found online at http://dx.doi.org/10.1186/s12872-015-0019-z.
An erratum to this article is available at http://dx.doi.org/10.1186/s12872-015-0019-z.
The authors declare that they have no competing interests.
ZXL and LLM carried out the molecular genetic studies, participated in the sequence alignment and manuscript preparation. FH and JH carried out the immunoassays. WTZ participated in the sequence alignment. CYD, SX and WGL participated in the design of the study and performed the statistical analysis. HSZ conceptualized the study, participated in the study design, oversaw execution of the designed experiments and helped prepare the manuscript. All authors read and approved the final manuscript.
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).
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.
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).
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.
Li T-S, Cheng K, Malliaras K, Smith RR, Zhang Y, Sun B, Matsushita N, Blusztajn A, Terrovitis J, Kusuoka H: Direct comparison of different stem cell types and subpopulations reveals superior paracrine potency and myocardial repair efficacy with cardiosphere-derived cells. J Am Coll Cardiol. 2012, 59 (10): 942-953. 10.1016/j.jacc.2011.11.029. CrossRefPubMedPubMedCentral
Gmeiner M, Zimpfer D, Holfeld J, Seebacher G, Abraham D, Grimm M, Aharinejad S: Improvement of cardiac function in the failing rat heart after transfer of skeletal myoblasts engineered to overexpress placental growth factor. J Thorac Cardiovasc Surg. 2011, 141 (5): 1238-1245. 10.1016/j.jtcvs.2010.10.054. CrossRefPubMed
Kandalam V, Basu R, Abraham T, Wang X, Soloway PD, Jaworski DM, Oudit GY, Kassiri Z: TIMP2 deficiency accelerates adverse post–myocardial infarction remodeling because of enhanced MT1-MMP activity despite lack of MMP2 activation. Circ Res. 2010, 106 (4): 796-808. 10.1161/CIRCRESAHA.109.209189. CrossRefPubMed
Li PL, Li CX, Xue YT, Li HH, Liu HB, He XX, Yu GL, Guan HS: An HPLC method for microanalysis and pharmacokinetics of marine sulfated polysaccharide PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles in rat plasma. Mar Drugs. 2013, 11 (4): 1113-1125. 10.3390/md11041113. CrossRefPubMedPubMedCentral
Iwasaki H, Kawamoto A, Tjwa M, Horii M, Hayashi S, Oyamada A, Matsumoto T, Suehiro S, Carmeliet P, Asahara T: PlGF repairs myocardial ischemia through mechanisms of angiogenesis, cardioprotection and recruitment of myo-angiogenic competent marrow progenitors. PLoS ONE. 2011, 6 (9): e24872-10.1371/journal.pone.0024872. CrossRefPubMedPubMedCentral
Takeda Y, Uemura S, Iwama H, Imagawa K-I, Nishida T, Onoue K, Takemoto Y, Soeda T, Okayama S, Somekawa S: Treatment with recombinant placental growth factor (PlGF) enhances both angiogenesis and arteriogenesis and improves survival after myocardial infarction. Circ J. 2009, 73 (9): 1674-1682. 10.1253/circj.CJ-08-1067. CrossRefPubMed
Viita H, Markkanen J, Eriksson E, Nurminen M, Kinnunen K, Babu M, Heikura T, Turpeinen S, Laidinen S, Takalo T: 15-Lipoxygenase-1 prevents vascular endothelial growth factor A–and placental growth factor–induced angiogenic effects in rabbit skeletal muscles via reduction in growth factor mRNA levels, NO bioactivity, and downregulation of VEGF receptor 2 expression. Circ Res. 2008, 102 (2): 177-184. 10.1161/CIRCRESAHA.107.155556. CrossRefPubMed
Cianfarani F, Zambruno G, Brogelli L, Sera F, Lacal PM, Pesce M, Capogrossi MC, Failla CM, Napolitano M, Odorisio T: Placenta growth factor in diabetic wound healing: altered expression and therapeutic potential. Am J Pathol. 2006, 169 (4): 1167-1182. 10.2353/ajpath.2006.051314. CrossRefPubMedPubMedCentral
Kandalam V, Basu R, Moore L, Fan D, Wang X, Jaworski DM, Oudit GY, Kassiri Z: Lack of tissue inhibitor of metalloproteinases 2 leads to exacerbated left ventricular dysfunction and adverse extracellular matrix remodeling in response to biomechanical StressClinical perspective. Circulation. 2011, 124 (19): 2094-2105. 10.1161/CIRCULATIONAHA.111.030338. CrossRefPubMed
Nishida Y, Miyamori H, Thompson EW, Takino T, Endo Y, Sato H: Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2. Cancer Res. 2008, 68 (21): 9096-9104. 10.1158/0008-5472.CAN-08-2522. CrossRefPubMed
Douglas S, Davis S, Illum L: Nanoparticles in drug delivery. Crit Rev Ther Drug Carrier Syst. 1987, 3 (3): 233- PubMed
Bala I, Hariharan S, Kumar MR: PLGA nanoparticles in drug delivery: the state of the art. Crit Rev Therap Drug Carrier Syst. 2004, 21 (5): 387-422. 10.1615/CritRevTherDrugCarrierSyst.v21.i5.20. CrossRef
- RETRACTED ARTICLE: Cardioprotective activity of placental growth factor in a rat model of acute myocardial infarction: nanoparticle-based delivery versus direct myocardial injection
- BioMed Central
Neu im Fachgebiet Kardiologie
Mail Icon II